tag:blogger.com,1999:blog-41626015665414626152024-02-21T06:34:30.511-08:00The MixThe news blog of the University of Alabama at Birmingham's research enterprise. Mix of topics. Mix of biochemicals in the lab and the body. Mix of disciplines that set UAB apart.
UAB. Knowledge that will change your world.Meghanhttp://www.blogger.com/profile/15726918929311875236noreply@blogger.comBlogger105125tag:blogger.com,1999:blog-4162601566541462615.post-29497771104556758672014-12-27T12:05:00.000-08:002014-12-29T08:15:44.648-08:00The Mix has movedStay up to date with the latest stories and insights from UAB research at our new location, <a href="http://www.uab.edu/mix">www.uab.edu/mix</a>.<br />
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Unknownnoreply@blogger.com0tag:blogger.com,1999:blog-4162601566541462615.post-26352593248688880932014-12-22T11:49:00.000-08:002014-12-27T12:03:42.422-08:00Change agent: Creating new scans to track brain diseases<div class="separator" style="clear: both; text-align: center;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEh8quIWou0mdG2HxeJ8llmjmHEwXDixIIU6kvIje18zGBxgGOoIqO7_QjIqZ8pnJsATDUx2LFC0U9fVygXJRCWuOWwpFl6ewhJeb18W9SqrOgt1VVZP49YQXcvSYZVvmMDpoH56xIVbMZw0/s1600/kessler.jpg" imageanchor="1" style="clear: left; float: left; margin-bottom: 1em; margin-right: 1em;"></a><a href="https://www.blogger.com/blogger.g?blogID=4162601566541462615" imageanchor="1" style="clear: left; float: left; margin-bottom: 1em; margin-right: 1em;"></a><img border="0" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEh8quIWou0mdG2HxeJ8llmjmHEwXDixIIU6kvIje18zGBxgGOoIqO7_QjIqZ8pnJsATDUx2LFC0U9fVygXJRCWuOWwpFl6ewhJeb18W9SqrOgt1VVZP49YQXcvSYZVvmMDpoH56xIVbMZw0/s1600/kessler.jpg" /></div><div class="separator" style="clear: both; text-align: center;"><a href="https://www.blogger.com/blogger.g?blogID=4162601566541462615" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"></a></div><b>Seven weeks after weight-loss surgery, a group of women have seen significant changes in their body shapes and sizes.</b> They’re each down 20 to 30 pounds, but that’s not the only change their bodies are going through.<br />
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The women’s weight loss is caused by a change in appetite, which results from changes in brain function, explains UAB neuroradiologist Robert Kessler, M.D. (pictured above in UAB's Advanced Imaging Facility). On positron emission tomography (PET) scans, Kessler can see an obvious transformation in the women’s brains, particularly in dopamine neurotransmission.<br />
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Using a specialized brain PET scan that he has developed, Kessler can visualize levels of dopamine receptors — molecules that help transmit the brain’s messages of motivation and reward. Before surgery, the women had increased levels of the receptors, which appear on the PET scans as glowing white patches throughout the brain. But after their surgeries, these changes have faded; the women’s brains exhibit a more balanced map of dopamine receptors. In real-world terms, Kessler thinks, these tempered receptor levels reflect a shift to a more normal reward perception, helping the women control their appetites after surgery.<br />
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Obesity — and the drive to overeat — isn’t the only pathology that Kessler can see when he peers into people’s brains with a PET scan. During the past 30 years, he has helped illuminate changes to the brain that might underlie schizophrenia, drug addiction, depression and dementia, among other disorders. By looking at a person’s brain PET scan and carefully measuring the levels of neurotransmitter function, Kessler can tell whether someone is <a href="http://www.ncbi.nlm.nih.gov/pubmed/19118170">more prone to taking risks than average</a>, whether they’re more of a “slacker” or a “go-getter,” and whether or not they have “the ability to experience rewarding stimuli in a normal manner or if they have lost that ability,” he said.<br />
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<tr> <td class="tr-caption" style="text-align: center; width: 280px;">Find out how a cyclotron works, and what makes UAB’s new cyclotron unique among U.S. academic medical centers, in the video above and in <a href="http://www.uab.edu/uabmagazine/cyclotron">this feature</a> from UAB Magazine.</td> </tr>
</tbody> </table>Kessler, who joined the UAB faculty in 2013 as director of neurochemical brain imaging and PET neurotracer development in the <a href="http://www.uab.edu/medicine/radiology/">Department of Radiology</a>, says these specialized PET scans are paving the way toward a new level of understanding of brain diseases.<br />
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“At a very basic scientific level, there’s no other technology that can look at the human brain and inform you about specific molecules and receptors,” Kessler said. At UAB, he’s taking advantage of the university’s <a href="http://www.uab.edu/medicine/radiology/advanced-imaging-facility">TR24 cyclotron</a> — the largest at any U.S. academic medical center — to develop new PET scans. And he has launched collaborations with UAB researchers across the psychiatric and neurological sciences to help them apply his techniques to even more questions.<br />
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<h3>Focusing on Receptors</h3>As a medical student, resident and fellow in the 1970s, Kessler first became interested in the human brain at a time that clinicians had few methods to visualize the organ. Surgeons could physically see the outer layers of the brain when they opened the skull for an operation, or pathologists could dissect an autopsied brain; but viewing the activity — in a living human — of the molecules that make up the brain’s electrical pathways wasn’t possible.<br />
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In 1977, Kessler joined a lab at the National Institutes of Health just as this was changing. One of his mentors there became the first to use a PET scan to visualize the activity of the brain. The earliest scans, rather than pinpointing specific receptors as Kessler does now, were designed to simply show which cells in the brain were undergoing metabolism — a sign of activity — at any given moment.<br />
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But the basic idea has been the same for more than three decades now: A patient gets an injection of a radioactive tracer into their bloodstream. Depending on the design of the tracer, it accumulates in particular organs or cells of the body. Then, a PET machine is used to measure the location of the accumulated radioactivity.<br />
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“It quickly became clear to me that PET was going to become an important tool for understanding the brain,” Kessler said. “And we began to use it to look at everything from brain tumors and schizophrenia to aging and dementia.”<br />
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As Kessler immersed himself in the new technology, first at NIH and then at Vanderbilt University, he helped develop new tracers that would pave the way for the rest of his career: 18F-Fallypride, and later 18F-FPEB. Rather than building up in all metabolizing brain cells, these radioactive molecules bind specifically to dopamine and glutamate receptors.<br />
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Among the first questions Kessler asked with 18F-Fallypride was ‘What are the effects of antipsychotic drugs on the brains of patients with schizophrenia?’ A new class of antipsychotic drug had recently been developed; the drugs had fewer side-effects than older versions, but researchers didn’t know why. Kessler and his collaborators discovered that the new drugs targeted different areas of the brain than the old drugs, offering not only an explanation for the differences, but a way to test future drugs for their efficacy.<br />
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Dopamine had also already become known as a chemical that mediates reward-seeking behavior and pleasure. So Kessler’s lab began to look at how levels of the dopamine receptor and the effects of dopamine release on dopamine receptors might relate to drug abuse, impulse control, addiction and the ability to feel pleasure.<br />
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“People who are depressed lose their ability to enjoy rewards and experience the pleasures of life; people who are addicted have very distorted reward functions where they crave just one reward,” Kessler said. “We showed that dopamine plays a key role in all of these.”<br />
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<tr><td class="tr-caption" style="text-align: center;">These are 18F-Fallypride PET images of dopamine D2 type receptors, averaged across several normal subjects. There are high levels of these receptors (red color) in deep brain structures and lower levels in the cortex. These include the basal ganglia and thalamus (A), amygdala and temporal cortex (B), and substantia nigra (C). These regions are concerned with movement, emotion and cognition.</td></tr>
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<h3>The Future of Brain PET</h3>PET scans offer the most direct way to observe what happens at a molecular level in the brain when someone develops, or recovers from, a psychiatric disorder or addiction, Kessler says. Drug developers and pharmaceutical companies now use PET scans to fine-tune prospective new treatments, he notes. If they know they need to lower the number of dopamine receptors in one area of the brain, for instance, they can use PET scans to determine which drugs, and drug dosages, effectively achieve this.<br />
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One of the ongoing challenges in the field, Kessler says, is developing new tracers. With UAB’s new cyclotron, Kessler says he has the tools at his fingertips to continue developing and perfecting tracers that bind to different receptors in the brain. He’s already begun work with the neurotransmitter glutamate; like dopamine, glutamate can be studied through PET tracers that bind to glutamate receptors. And glutamate is thought to have roles in autism, Huntington’s disease, Parkinson’s and anxiety disorders, among other things.<br />
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This fall, Kessler launched a study examining glutamate receptors in the brains of addicts as they voluntarily withdraw from methamphetamine. The findings — if they show key differences from normal brains — could lead to new drugs to help meth addicts quit their addiction. Studies on Parkinson’s, depression and Alzheimer’s disease are also in the works with UAB collaborators.<br />
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Although “this is a tough area to work in for many reasons,” Kessler said — from the vagaries of chemical half-lives to the sheer complexity of the brain itself — he wouldn’t have it any other way. “You just can’t get this kind of information anywhere else.”Unknownnoreply@blogger.com0tag:blogger.com,1999:blog-4162601566541462615.post-68612767238779033202014-12-15T11:07:00.001-08:002014-12-15T11:08:27.028-08:00Equations against cancer: Using math to predict a tumor's path<div class="separator" style="clear: both; text-align: center;">
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</strong> <strong>Hassan Fathallah-Shaykh, M.D., Ph.D., believes that math can transform medicine, and he has the numbers to prove it.</strong><br />
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In the clinic, this UAB <a href="http://www.uab.edu/medicine/neurology/">neurologist</a> specializes in treating brain tumors. In his lab at the <a href="http://www3.ccc.uab.edu/">Comprehensive Cancer Center</a>, Fathallah-Shaykh, who is also a professor of <a href="http://www.uab.edu/cas/mathematics/">mathematics</a> at UAB, wields equations as well as petri dishes. His mathematical models of cancer behavior are offering new insights on tumor growth. Eventually, they could be used to personalize treatment based on the unique characteristics of each patient’s cancer cells and anatomy.<br />
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Fathallah-Shaykh is one of a growing number of researchers worldwide exploring the field of mathematical biology, which “uses mathematical tools to generate models of biological problems,” he said. Building mathematical models based on the current understanding of a disease, for example, allows researchers to “test whether the assumptions are accurate,” Fathallah-Shaykh said.<br />
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<tr><td class="tr-caption" style="text-align: center;">Hassan Fathallah-Shaykh</td></tr>
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Models can also be used “to test a treatment strategy, understand why it fails or works, and optimize therapy,” he added. The results of these tests can also generate new insights and hypotheses that can be investigated in the laboratory. “None of these goals can be achieved by traditional methods,” Fathallah-Shaykh said.<br />
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Model Behavior</h3>
Working with colleagues at the University of Bordeaux, and UAB graduate student Elizabeth Scribner, Fathallah-Shaykh has created an elegant model of the aggressive brain cancer glioblastoma multiforme (GBM). It produces simulations on the scale of clinical MRI scans, so that its predictions can be tested directly against patient data. In a paper <a href="http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0115018">published on Dec. 15</a> in PLOS ONE, the researchers demonstrated that their model can reproduce the typical GBM growth patterns seen on patient scans. They also revealed its value as a research tool.<br />
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The model predicted a previously unknown pattern of tumor growth in patients with recurrent GBM treated with the anti-angiogenesis drug bevacizumab. This growth, powered by a cycle of proliferation and brain invasion, is characterized by an expanding area of invasive cells and dead cells known as necrosis, the researchers say. A subsequent search of 70 patient MRI scans by the researchers turned up the same pattern in 11 cases.<br />
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<b>“We hope to tailor radiation therapy, chemotherapy and other treatments based on a personalized model of a patient’s tumor.”</b></div>
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That pattern explains the disappointing results of recent Phase III clinical trials of anti-angiogenesis therapies against GBM, the researchers say. Anti-angiogenesis drugs attempt to kill tumors by preventing them from growing new blood vessels. But the model demonstrated how GBM cells can flee from the oxygen-depleted treatment area — and quickly begin expanding again as soon as therapy stops or the tumor becomes resistant to the drugs. (For more on the model and these findings, see “SimTumor,” below.)<br />
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“We’ve shown that we can predict new insights on cancer behavior,” Fathallah-Shaykh said. The results have already spurred Fathallah-Shaykh to pursue new therapies in his lab to limit tumor mobility. Ultimately, the researchers hope to use their model to personalize therapy to the unique characteristics of a patient’s tumor. They could do that by analyzing the existing growth pattern of a tumor and building that into the model’s parameters. Then they could simulate its future behavior on a virtual MRI slice that reproduces the unique anatomy of the patient’s brain. “We hope to tailor radiation therapy, chemotherapy and other treatments based on a personalized model of a patient’s tumor,” said Fathallah-Shaykh.<br />
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Advancing Mathematical Biology Research</h3>
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Hassan Fathallah-Shaykh, M.D., Ph.D., is a perfect ambassador for the highly interdisciplinary field of mathematical biology. In addition to his faculty positions in the departments of <a href="http://www.uab.edu/medicine/neurology/">Neurology</a>, <a href="http://www.uab.edu/cas/mathematics/">Mathematics </a>and <a href="http://www.uab.edu/medicine/cdib/">Cell, Developmental and Integrative Biology</a>, he holds an appointment in the <a href="http://www.uab.edu/engineering/home/">School of Engineering</a>. That breadth of expertise has enabled him to establish collaborations with researchers at UAB and at several international universities, and he is working to interest more colleagues in mathematical biology.<br />
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This spring, Fathallah-Shaykh helped organize a symposium on the topic as part of the College of Arts and Sciences’ Interdisciplinary Innovation Forum series. The meeting attracted some of the mathematical biology’s most famous names. Meanwhile, he is helping to attract new talent to the discipline by teaching undergraduate and graduate courses on Mathematical Biology in the <a href="http://catalog.uab.edu/undergraduate/collegeofartsciences/mathematics/#courseinventory">math department</a>.<br />
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“It is quite clear that the next great advances in medicine cannot happen without math,” Fathallah-Shaykh said. “These are exciting times.”</td> </tr>
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From Flies to Colon Cancer</h3>
Since he joined the UAB faculty in 2008, Fathallah-Shaykh has been developing ever more advanced models to predict the behavior of biological networks. He began by building a model of the molecular clock in a fruit fly’s brain. Despite the fly’s tiny size, it’s a challenging puzzle. The clock is a tangled web of positive and negative feedback loops, with five different genes producing proteins that inhibit and activate one another (as well as themselves, in some cases) in a regular cycle.<br />
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First, Fathallah-Shaykh and his collaborators “showed we can replicate everything the clock is known to do,” he said. Then they proved it was a useful research tool, answering a perplexing question about the fruit-fly gene Clockwork Orange that had stumped biologists for years.<br />
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The researchers next adapted their model to track the developing neural networks in fruit-fly embryos. To do this, they utilized the Kalman filter, a mathematical technique to analyze and predict changes that helps track planes in flight. Now, “we’re using the model to study molecular networks in colon cancer,” Fathallah-Shaykh said.<br />
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Coping with an Information Explosion</h3>
Fathallah-Shaykh has always been fascinated with math. “It’s like a symphony; it’s beautiful,” he said. “But it’s also very applicable.” He cemented the connection between medicine and math as a neurologist at Rush University Medical Center in Chicago when he enrolled in a doctoral program in mathematics at the nearby University of Illinois–Chicago. “I would go to class in between patients,” he said.<br />
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Math is essential to making progress against the toughest questions in medicine, Fathallah-Shaykh contends. To illustrate the problems that researchers face, he points to a chart of all the known molecular pathways involved in Alzheimer’s disease. It’s a mass of interlocking loops and tangles that <a href="http://www.alzpathway.org/AlzPathway.html">fills an entire page</a>. Researchers specialize in tiny sections of this wiring diagram, but understanding how it all works together is another problem entirely. Even worse, these networks are intertwined in such a way that multiple paths can lead to the same destination. That may help explain why treatments that work beautifully in isolated cell lines in a lab so often fail when they encounter the complex networks of the body.<br />
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There’s another wrinkle. “Cells migrate, they communicate, they interact with one another over time,” said Fathallah-Shaykh. The waves of mutations, which are a hallmark of cancer, make the problem particularly complex, he noted. “Whole pathways are deleted and new connections start turning up.” It’s a perfect example of a nonlinear dynamic system, like the weather or the stock market, in which slight changes in one parameter can lead to wildly diverging outcomes.<br />
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The good news, said Fathallah-Shaykh, is that “mathematics has very rich tools” to model just these types of systems, as he has demonstrated with his cancer simulations. But this work has another exciting element for Fathallah-Shaykh as a mathematician: It opens new horizons in math theory. “Equations have already been developed from biological problems,” he said, “and there is very strong evidence that they will produce spectacular advances in mathematics.”<br />
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SimTumor</h3>
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<strong>At the heart of Hassan Fathallah-Shaykh’s new mathematical model of glioblastoma multiforme (GBM) are 10 partial differential equations. Here’s how it works — and what it has revealed about GBM behavior.</strong><br />
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Formula 10</h3>
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Equations track each of four different cell types, with unique rules of behavior.</div>
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<strong>Proliferative GBM cells</strong> (P), which make up the bulk of the tumor, divide but don’t move.</div>
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<strong>Invasive GBM cells</strong> (I), found on the fringes of the tumor, move but don’t divide.<br />
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Healthy <strong>brain cells</strong> (B) neither divide nor move, although they are displaced by the growing tumor.</div>
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Cells in the center of the tumor, cut off from nourishing blood vessels, are starved of oxygen (hypoxia) and die, becoming <strong>necrotic cells</strong> (N).</div>
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The remaining six equations track angiogenesis (new blood vessel formation), oxygen levels, and rates of necrosis and cell division.</div>
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Built for Speed</h3>
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Fathallah-Shaykh’s first GBM model, <a href="http://www.ncbi.nlm.nih.gov/pubmed/25149139">published in August 2014</a> in the Bulletin of Mathematical Biology, consisted of many more equations. It required a supercomputer, and several days, to run. The model published in PLOS ONE can run in 50 seconds on a typical desktop computer.</div>
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And They’re Off!</h3>
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The simulation begins with a tiny clump of tumor cells surrounded by healthy brain. As the program continues over several virtual weeks, this mass expands in the characteristic manner seen on patient MRIs, with a dark region of necrotic cells in the center, surrounded by a large group of proliferative cells and an outer rim of invasive cells.</div>
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Grow or Go</h3>
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The model’s main assumption is that proliferative cells can turn into invasive cells in hypoxic conditions. This is in keeping with the “grow or go” hypothesis of GBM behavior, which says that low oxygen levels spur GBM cells to flee the dying core of the tumor. When these new invasive cells reach healthy, oxygenated areas of brain, they switch back into proliferative mode and start growing again.</div>
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How GBM Escapes Anti-Angiogenesis Therapy</h3>
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As tumors grow, cells at the core lose contact with nourishing blood vessels and die.</div>
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To get around this problem, tumors release VEGF (vascular endothelial growth factor), which induces the body to create new blood vessels (a process known as angiogenesis). In fact, the well-known Folkman Hypothesis states that tumors must be able to induce blood vessel growth in order to keep growing.</div>
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Clinicians had high hopes that anti-angiogenesis medications such as bevacizumab (Avastin), could keep tumor growth in check. But two high-profile Phase III clinical trials, which released results in early 2014, found that bevacizumab therapy did not prolong overall survival in patients with recurrent GBM, although it did extend progression-free survival and patient quality of life.</div>
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Fathallah-Shaykh’s model, programmed to simulate the effects of anti-angiogenesis therapy, reveals an explanation for this “unusual clinical finding.” When bevacizumab therapy causes oxygen levels to drop, proliferative cells turn into invasive cells and flee the scene. When they reach an area with sufficient oxygen, they convert back into proliferative cells and begin a new cycle of growth. This sets up the tumor for rapid “rebound” growth as soon as it becomes resistant to bevacizumab or therapy is discontinued. That explains why patients treated with bevacizumab in the recent trials didn’t experience any increase in overall survival rates over those who were not treated.</div>
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Toward New Treatment Approaches</h3>
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The model underlines the importance of better understanding the molecular mechanisms of brain cell invasion, particularly the active transport of invasive cells toward healthy brain regions, says Fathallah-Shaykh.</div>
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There are currently no available biomarkers to identify the quantity of invasive cells in a patient’s tumor. But finding such a biomarker, and drugs that can target these cells to prevent tumor migration, is a current research focus in Fathallah-Shaykh’s lab. “If we’re going to kill these tumors,” he said, “we have to target the cells that are invading.”</div>
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Unknownnoreply@blogger.com0tag:blogger.com,1999:blog-4162601566541462615.post-55315674626641972482014-12-02T11:17:00.001-08:002014-12-02T11:17:32.098-08:00Creating a roadmap to bring innovative medical technologies to market<div class="separator" style="clear: both; text-align: center;">
<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhA3hq2wuOrRIgf6fRe6vSUtOuL0cQKTEc-n0dPgIJgfC4S16M_rj8ET8AzP5wixV_ladBOSAjQ_-sB3AecHnilBnfmFZCYhJsXA-kRvzJhkunYrCrAcJU0m5-18Pau0PE024pls8kndR7C/s1600/mix_Medical-Device-Innovation-Surgery-illus.jpg" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhA3hq2wuOrRIgf6fRe6vSUtOuL0cQKTEc-n0dPgIJgfC4S16M_rj8ET8AzP5wixV_ladBOSAjQ_-sB3AecHnilBnfmFZCYhJsXA-kRvzJhkunYrCrAcJU0m5-18Pau0PE024pls8kndR7C/s1600/mix_Medical-Device-Innovation-Surgery-illus.jpg" /></a></div>
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<b>Robert Hergenrother, Ph.D., isn’t a surgeon, but he has done some of his best work in the operating room. </b>In his three decades in the medical device industry, Hergenrother has led engineering teams that have created 15 products, including new technologies for use in brain surgery, wound care and diagnosing disease. “When you have a surgeon come up to you and say, ‘If it wasn’t for your device, I couldn’t have helped that patient,’ that’s pretty powerful,” Hergenrother said.<br />
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As the director of the new <a href="http://www.uab.edu/news/innovation/item/5498-southern-research-institute-and-uab-partner-to-develop-life-changing-medical-devices">Alliance for Innovative Medical Technologies </a>(AIMTech), Hergenrother is focused on creating the next generation of life-changing medical devices in Birmingham. AIMTech is a partnership between UAB and <a href="http://www.southernresearch.org/">Southern Research Institute</a>, modeled after the two institutions’ successful <a href="http://www.uab.edu/medicine/adda/">Alabama Drug Discovery Alliance</a>. It will identify promising projects already in development at both institutions and launch new projects that meet pressing clinical needs, Hergenrother explains. AIMTech will provide investment and support to bring these projects through clinical trials and FDA approval. Then the devices will be spun off in startup companies or licensed to major medical device makers.<br />
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Scouting for the Next Big Thing</h3>
Hergenrother, who also has a faculty appointment in the <a href="http://www.uab.edu/engineering/home/departments-research/bme">UAB Department of Biomedical Engineering</a>, is now meeting with clinicians and researchers across campus. “In one day I can go from drug delivery to sports medicine to physical therapy to radiology,” he said. “I get to see a lot of different ideas and work with people who really are excited about moving these ideas forward.”<br />
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<tr><td style="text-align: center;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhQLw53Mk9N5TtG4GLh8jK47JeGER-JDuJTGCad84XJu5eFYuOxo4JMew30RU-MrmhCp1t8mQg_YmDbuRqG7FWSffF8Z3ok1WATZ955x-VbegIAlh9WowwvsYHyM2KMqnt4Xd-8Ls4-xrxi/s1600/Bob_Hergenrother_RT_350.jpg" imageanchor="1" style="clear: right; margin-bottom: 1em; margin-left: auto; margin-right: auto;"><img border="0" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhQLw53Mk9N5TtG4GLh8jK47JeGER-JDuJTGCad84XJu5eFYuOxo4JMew30RU-MrmhCp1t8mQg_YmDbuRqG7FWSffF8Z3ok1WATZ955x-VbegIAlh9WowwvsYHyM2KMqnt4Xd-8Ls4-xrxi/s1600/Bob_Hergenrother_RT_350.jpg" /></a></td></tr>
<tr><td class="tr-caption" style="text-align: center;">AIMTech director Robert Hergenrother (right) and David Brown (left)<br />test new rehabilitation technologies in Brown's lab. AIMTech's goal<br />is to develop promising projects into market-ready medical devices.</td></tr>
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Some projects are already highly developed, Hergenrother says, including high-tech rehabilitation devices created in the lab of David Brown, Ph.D., in the <a href="http://www.uab.edu/shp/pt/">UAB Department of Physical Therapy</a>. Others are simply intriguing concepts. Hergenrother recently met with a surgeon who wants to develop a new tool for cartilage repair. “He had an idea and a drawing,” Hergenrother said. “We were able to come in and make a quick prototype and put it in his hands. He was fired up. It’s a great way to just start answering questions: ‘Is this working, yes or no?’”<br />
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Conversations with UAB clinicians will lead to opportunities to create entirely new types of devices. “We want to focus on what is causing people problems now,” Hergenrother said. One of his main jobs, he explains, is to connect clinicians with researchers who can develop solutions to meet their needs.<br />
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Hergenrother, who holds 18 patents of his own, understands the thrill of a new invention. But creating a successful medical device isn’t a matter of innovation alone, he points out. As part of the initial scouting phase of the program, “I’m asking investigators to work with me to conduct 20 interviews with the people who will be the ultimate end-users of their product,” he said. “They need to find out how people are doing the job now, what the current solutions are and what advantages their product has to offer.”<br />
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Competitive Advantages</h3>
Major medical device companies are always eager for new ideas, Hergenrother says. As the industry matures — it is projected to grow by nearly 21 percent by 2016 — those companies are focusing more on international expansion and production efficiencies, he adds. “They’re relying on smaller companies and universities to drive innovation.”<br />
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Top Targets</h3>
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AIMTech will initially focus on developing projects in five key areas:</td> </tr>
<tr> <td>Cardiology</td> <td><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhQ2khGUGNqoh5jad8xtsRTgiJq3W48QjY9hLvfLF1h06vI3ILIzbTCLatisMUYtg42H6enujQWgm8ARcXEY1OsMSM5euVSy4BzUVyEvl9srRPyQQxDhtPXXWphuQ_spC5dlhqiZeLIrL7I/s1600/75_ekg-button.png" imageanchor="1"><img border="0" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhQ2khGUGNqoh5jad8xtsRTgiJq3W48QjY9hLvfLF1h06vI3ILIzbTCLatisMUYtg42H6enujQWgm8ARcXEY1OsMSM5euVSy4BzUVyEvl9srRPyQQxDhtPXXWphuQ_spC5dlhqiZeLIrL7I/s1600/75_ekg-button.png" /></a></td> </tr>
<tr> <td>Orthopedics</td> <td><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgbJ0heW1iZCwQ85fytXlpq-azZrjoMQVOGwNBjSgmgU5uVaRFbwiO8QGsW9Amd8js5OgZOTQuBJxtPfeyveiaQiq5E3z5LH4WFiYvoDkNdmmNhJJK_2b8TLke4bXjsQgKoTji-n5njht1c/s1600/75_bone-button.png" imageanchor="1"><img border="0" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgbJ0heW1iZCwQ85fytXlpq-azZrjoMQVOGwNBjSgmgU5uVaRFbwiO8QGsW9Amd8js5OgZOTQuBJxtPfeyveiaQiq5E3z5LH4WFiYvoDkNdmmNhJJK_2b8TLke4bXjsQgKoTji-n5njht1c/s1600/75_bone-button.png" /></a></td> </tr>
<tr> <td>Ophthalmology</td> <td><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEj7AsWmJ__fFVZX6Kr1ErjR4gjlwP5GWJmQMcFz-U4XWEE-pIFBQXCTZ_4dhQ70i7OruSJZiTY0MvLkx8D6DO0RqzPCUi1ue6OcrLKg3Njx8S8T6OM9a6vthblVbL7swTpbpfqK2dEIrzBk/s1600/75_eye-button.png" imageanchor="1"><img border="0" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEj7AsWmJ__fFVZX6Kr1ErjR4gjlwP5GWJmQMcFz-U4XWEE-pIFBQXCTZ_4dhQ70i7OruSJZiTY0MvLkx8D6DO0RqzPCUi1ue6OcrLKg3Njx8S8T6OM9a6vthblVbL7swTpbpfqK2dEIrzBk/s1600/75_eye-button.png" /></a></td> </tr>
<tr> <td>Rehabilitation Engineering</td> <td><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEiOA0E4mrLiV3kV-ps2ZPe-uE9839mWP4pxKznNQ5OzKLREdoxA4SYfb74gDYhu9k5G6HvwAuta3z7LiKkSNXgcpVRdYW_tSthhC8_Nq3uSvLZuu-nu6dh_F5PUkroaTvmg4Ou-bJJ2X8wt/s1600/75_rehab-button.png" imageanchor="1"><img border="0" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEiOA0E4mrLiV3kV-ps2ZPe-uE9839mWP4pxKznNQ5OzKLREdoxA4SYfb74gDYhu9k5G6HvwAuta3z7LiKkSNXgcpVRdYW_tSthhC8_Nq3uSvLZuu-nu6dh_F5PUkroaTvmg4Ou-bJJ2X8wt/s1600/75_rehab-button.png" /></a></td> </tr>
<tr> <td>Trauma</td> <td><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEje-60E-zBdQ97ugaQpYLOhVctT0YdgR9eOPeNROwWvIXN8IQRdvzt2aHynTZnwmwHWdwVtoqfHxcjLQfFxEmMrtcG6iuO0YViu8UeLeNHu-mcBsaEzhWg3PXnV_yrpJSaU4kQI-w3NGxLQ/s1600/75_ambulance-button.png" imageanchor="1"><img border="0" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEje-60E-zBdQ97ugaQpYLOhVctT0YdgR9eOPeNROwWvIXN8IQRdvzt2aHynTZnwmwHWdwVtoqfHxcjLQfFxEmMrtcG6iuO0YViu8UeLeNHu-mcBsaEzhWg3PXnV_yrpJSaU4kQI-w3NGxLQ/s1600/75_ambulance-button.png" /></a></td> </tr>
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But companies aren’t as quick to make deals as they once were. In the past, “it was enough to have neat graphs and some bench data” to attract a licensing agreement with a device manufacturer, Hergenrother said. Today, the financial stakes are higher, and “companies want short- and long-term animal data, and even human data” before they are willing to invest in unproven technology.<br />
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In industry jargon, this is known as “de-risking” — building up the scientific and marketing data necessary to justify a major financial investment. AIMTech will be able to supply that proof by tapping into the combined capabilities of Southern Research and UAB.<br />
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UAB’s <a href="http://www.uab.edu/research/innovation/">Institute for Innovation and Entrepreneurship</a> (IIE) will vet the intellectual property position of every project that enters the AIMTech program. IIE and Southern Research will also evaluate potential market size, regulatory pathways and reimbursement strategies so that only the strongest, most market-ready technologies advance through AIMTech’s pipeline. Southern Research has extensive experience in assembling product-development systems and negotiating the regulatory requirements of clinical trials and FDA approvals, Hergenrother notes. “Someone has to do that work,” he said. “If we can take our projects further along than another university, ours will be more attractive to potential partners.”<br />
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AIMTech’s ultimate mission is to get life-changing products to market as quickly as possible, Hergenrother says. “We always want to keep in mind why we’re doing this. It’s not to get another patent, but to save lives. We have an opportunity to really make a difference here.”<br />
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<br />Unknownnoreply@blogger.com0tag:blogger.com,1999:blog-4162601566541462615.post-11698156910076669862014-11-18T08:01:00.001-08:002014-11-18T08:01:33.011-08:00Immunogenomics advances point to new biomarkers, therapies<div class="separator" style="clear: both; text-align: center;">
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<b>Next-generation gene-sequencing technology</b> and new data-analysis tools are pointing the way to fresh diagnostic and treatment approaches for autoimmune diseases, cancer and many other conditions. That was the message at Immunogenomics 2014, a recent conference hosted by Huntsville’s <a href="http://hudsonalpha.org/">HudsonAlpha Institute for Biotechnology</a> and Science magazine for researchers studying the interaction between genes and the immune system. The event was sponsored in partnership with UAB and its <a href="http://www.uab.edu/medicine/camac/">Comprehensive Arthritis, Musculoskeletal and Autoimmunity Center </a>(CAMAC).<br />
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Investigators from major national and international research institutions described how detailed profiles of immune cells could improve response to influenza vaccines and accelerate new treatments for emerging infectious diseases. They explained new immune-mediated links between microbial populations and cancer risk, and highlighted progress in understanding the pathogenesis of complex diseases such as multiple sclerosis.<br />
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“We now have the tools to examine these gene-disease associations in finer detail,” said S. Louis Bridges Jr., M.D., Ph.D., director of UAB’s <a href="http://www.uab.edu/medicine/rheumatology/">Division of Clinical Immunology and Rheumatology</a> and the CAMAC. Bridges is using genomic techniques to study the autoimmune condition rheumatoid arthritis. Bridges presented his research at Immunogenomics 2014, and served as chair of a session on the genetics of complex disease. “We’ve started to refine our analysis to home in on cells with an increasing degree of specificity,” Bridges said. “Technology is now allowing us to analyze in more detail specific subsets of cells, including ultimately at the single-cell level.”<br />
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From Associations to Biomarkers</h3>
Genomewide association studies have identified a host of genetic changes linked with disease. “Now investigators are looking at the functional effects of these polymorphisms,” Bridges said. “It could be that a polymorphism affects expression of a certain gene, or it may only affect expression of that gene in a certain cell type.” Bridges’ project, being performed in collaboration with UAB epidemiology chair Donna Arnett, Ph.D., and HudsonAlpha investigator Devin Absher, Ph.D., is examining genetic risk factors in African-Americans with RA.<br />
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<b>"We now have the tools to examine these gene-disease associations in finer detail," Bridges said. "We've started to refine our analysis to home in on cells with an increasing degree of specificity."</b></div>
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In his talk at Immunogenomics 2014, Bridges demonstrated that overexpression of the interferon gamma 2 receptor gene is strongly linked with severity of disease in African-American patients with RA. “Our next step is to see in which cells that particular expression occurs,” Bridges said. This work could ultimately point the way to biomarkers that tell clinicians which of several known signaling pathways is active in a patient with RA, guiding treatment decisions.<br />
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<h3>
Epigenetics and Therapeutics</h3>
Researchers are also focusing increasing attention on the ways gene expression is regulated dynamically in cells through epigenetic changes, says Robert P. Kimberly, M.D., director of the <a href="http://www.uab.edu/ccts/">UAB Center for Clinical and Translational Science</a>. Epigenetics refers to mechanisms that alter gene expression without changes in the actual DNA sequence. One of the most common epigenetic changes is methylation. When a methyl group attaches to the DNA base cytosine, it blocks the ability of the neighboring gene to be expressed.<br />
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Tracking and analyzing epigenetic markers implicated in a particular disease — such as systemic lupus erythematosus, one of Kimberly’s own research interests — could give clinicians crucial information on “if to treat, when to treat and also how to treat” that condition, he said.<br />
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For example, if a key risk gene is hypo-methylated in a patient — increasing the likelihood of the gene’s being expressed — “that could mean the patient is poised for a flare-up of disease,” Kimberly said. Another patient, who would look exactly the same to a clinician, would be much less likely to have a flare-up if that gene is hyper-methylated, he adds. “Understanding this epigenetic regulation, and eventually manipulating it to therapeutic advantage, is very exciting.” This research is a focus of several investigative teams at UAB, Kimberly says.<br />
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<tr><td class="tr-caption" style="text-align: center;">A “tree map” depicting the immune diversity in a patient diagnosed with Parkinson’s disease. Each rectangle represents a unique antigen receptor detected in the sample, and the size of each rectangle represents the relative frequency of that receptor within the sample. (Color is arbitrary.) Image courtesy iRepertoire.</td></tr>
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Profiling Immune Signatures</h3>
One advance highlighted by several presenters at Immunogenomics 2014 was immune repertoire sequencing. Researchers now understand that an individual’s immune response is based greatly on the specific cell populations, or “repertoire,” present in that individual. For both T and B cells, for example, millions of distinct variants are possible. The exact mix is determined by a person’s encounters with microbes, disease and other environmental exposures over a lifetime, explains HudsonAlpha investigator Jian Han, M.D., Ph.D., a 1991 graduate of UAB’s medical genetics doctoral program.<br />
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Everyone produces T cells, for example, Han says. “But which one of those naive T cells gets used is determined by if it met, and was activated by, its antigen.” By analyzing the variety of T and B cells present in a particular patient, or mapping the repertoire commonly found in a particular disease, researchers can identify biomarkers to aid in diagnosis and treatment, Han notes.<br />
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Han’s HudsonAlpha lab has pioneered the multiplex PCR technology needed to gather the massive amounts of data required for repertoire sequencing, and the analytical tools required to resolve that data into meaningful reports. His presentation at Immunogenomics 2014 focused on <a href="http://www.r10k.org/R10K/About_R10K.html">Repertoire10K</a>, a HudsonAlpha-funded project to sequence the immune repertoires of 10,000 patients: 100 with each of 100 critical diseases. The goal is to identify a signature in the immune repertoire for each disease. UAB researchers have been key contributors of the genetic samples that are critical to the project, Han says. In return, the investigators have access to state-of-the-art sequencing data that can advance their own studies. <br />
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Team-based Science</h3>
Collaborations between investigators at HudsonAlpha and UAB have taken place since the institute first opened in 2008, Kimberly says. But the new <a href="http://www.uab.edu/news/innovation/item/4824-uab-school-of-medicine-hudsonalpha-create-joint-center-for-genomic-medicine">UAB–HudsonAlpha Center for Genomic Medicine</a>, launched this summer, will increase these research partnerships and speed new discoveries in immunology, cancer, cardiovascular disease and many other fields, he notes.<br />
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Leveraging the strengths of each institution is critical as the scale of the research challenges becomes ever greater, Kimberly adds. “To understand what’s really happening in disease states, we’re going to have to be able to take all the data on genomics, epigenetics and more and figure out how to pull it all together,” he said.<br />
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That’s why UAB is also creating a new <a href="http://www.uab.edu/reporter/know-more/research/item/5136-informatics-institute-will-bridge-big-data-and-biomedical-research">Informatics Institute</a>. It will work in tandem with the UAB–HudsonAlpha Center for Genomic Medicine and a third initiative, the <a href="http://www.uab.edu/news/innovation/item/4826-uab-launches-three-initiatives-to-stimulate-personalized-medicine-care-research">UAB Personalized Medicine Institute</a>, to build the infrastructure and recruit the data scientists needed to succeed in this new era of research.<br />
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“It’s a major frontier right now,” Kimberly said. “The algorithms to combine all this data for the most part haven’t even been formulated yet. But it’s clear that the institutions that succeed in the future will be the innovators in this area.”<br />
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Unknownnoreply@blogger.com0tag:blogger.com,1999:blog-4162601566541462615.post-49729399829262553322014-11-06T04:17:00.002-08:002014-11-06T06:02:19.459-08:00Discovery route: Path to potential diabetes drugs began with a simple question<style>
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<tr><td class="tr-caption" style="text-align: center;">More than 12 years of research led Anath Shalev, M.D. (right, with Junqin Chen, Ph.D.) from a basic discovery to the first human trial of a new type of diabetes drug.</td></tr>
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<b>In 2002, diabetes researcher Anath Shalev, M.D., asked a basic question: </b>What gene in the insulin-producing islets of the human pancreas is most turned on by high levels of glucose, a hallmark of diabetes?<br />
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<div style="text-align: right;"></div>The answer has led the UAB endocrinologist to discover new cellular pathways in beta cells of the islets, pathways that are a key to diabetes progression or protection. Those discoveries have now opened the door to the first human trial of a potential diabetes drug with a mode of action different from any current diabetes treatment. <a href="http://www.uab.edu/news/innovation/item/5508">(Learn more about the trial, which will begin in early 2015, in this story.)</a><br />
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<tr><td style="text-align: center;"><iframe allowfullscreen="1" frameborder="0" height="180" src="//www.youtube.com/embed/0vdmwcRt5dc?rel=0&showinfo=0" style="float: right; margin: 15px;" width="320"></iframe> </td></tr>
<tr><td class="tr-caption" style="text-align: center; width: 280px;">Anath Shalev explains verapamil's protective effects against diabetes, and a new human clinical trial of the drug at UAB, in this video.</td></tr>
</tbody></table>Beta cells are critical in type 1 and type 2 diabetes. In both diseases, the cells are lost gradually due to programmed cell death (apoptosis); but the trigger for that programmed death was unknown. The loss of beta cells contributes to the progression of diabetes, a growing worldwide epidemic that affects more than 20 million people in the United States, making it the seventh leading cause of death and the source of complications like blindness and more than 40,000 lower limb amputations a year.<br />
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<h3>From Molecular Mechanisms to New Treatments</h3>The beta-cell gene that responded to the high glucose in <a href="http://www.ncbi.nlm.nih.gov/pubmed/?term=shalev+radonovich+2002">Shalev’s 2002 experiment</a> produces TXNIP (pronounced "ticks-nip"), a protein normally involved in controlling oxygen radicals in many types of cells but never known to be important in beta-cell biology. Its response to glucose was intriguing because TXNIP (thioredoxin-interacting protein) was already recognized as a regulator of thioredoxin. Overexpression of thioredoxin had previously been shown to prevent experimentally induced diabetes by inhibiting the programmed death of islet beta cells. Since TXNIP inhibits thioredoxin, and because Shalev had discovered that islet TXNIP was highly regulated by glucose, Shalev realized that TXNIP might have major implications for beta-cell biology.<br />
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What does it take to go from a basic microarray gene discovery to a human trial of a completely novel drug to treat diabetes?<br />
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A dozen years of elegant research unraveling the control and function of a protein called TXNIP.</div><span style="font-size: 14pt;"><b><br />
</b></span> Over the next dozen years, Shalev — who left the University of Wisconsin–Madison to head the <a href="http://www.uab.edu/medicine/diabetes/">UAB Comprehensive Diabetes Center</a> in 2010 — set out to reveal how TXNIP acts in cells at the molecular level, knowing that an understanding of those molecular mechanisms might point to possible new diabetes treatments. The payoff has been substantial: Using cell cultures, mouse models and pancreatic islets isolated from humans, the Shalev lab team has shown that manipulating TXNIP levels up or down in beta cells could exacerbate or protect against experimental diabetes.<br />
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Details about the research journey show the incremental steps that basic science takes, and how those connected steps sometimes lead to potential clinical impacts.<br />
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<h3>Controlling TXNIP to Treat Diabetes</h3><br />
<a href="http://www.ncbi.nlm.nih.gov/pubmed/15705778">In 2005,</a> the Shalev lab team found that beta-cell TXNIP levels are higher in mouse diabetes models, and that experimentally increasing TXNIP levels in rat beta cells in vitro led to increased programmed cell death, by means of a well-known trigger signal of apoptosis. The Shalev team also found that sugars in general, whether metabolized or not, turn the TXNIP gene on. This clue led them to a newly identified carbohydrate response element (ChoRE) in the TXNIP promoter that acts as a regulator of TXNIP.<br />
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<a href="http://www.ncbi.nlm.nih.gov/pubmed/18552236">In 2008,</a> the Shalev lab developed mice that had little or no TXNIP in their beta cells. These lower levels protected against experimental diabetes. The team also discovered that the lower levels sent a known signal that inhibited mitochondrial beta-cell death. Shalev wrote, “These results suggest that lowering beta-cell TXNIP production could serve as a novel strategy for the treatment of type 1 and type 2 diabetes by promoting endogenous beta-cell survival.”<br />
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<h3>An Approved Drug Offers Protection</h3><br />
<a href="http://www.ncbi.nlm.nih.gov/pubmed/22442301">In 2012,</a> the Shalev group tested an already approved oral drug that they had earlier found to reduce levels of TXNIP in heart cells. The drug — verapamil — is a calcium channel blocker used primarily to treat high blood pressure, but also to treat migraine headaches. Shalev’s team found that exposing in vitro beta cells or isolated human islets to verapamil reduced TXNIP expression, and halted programmed apoptotic death of beta cells. Furthermore, mice that were fed verapamil in their drinking water were protected from experimentally induced diabetes, and verapamil rescued mice that already had diabetes. The verapamil mice had lower TXNIP levels and less programmed beta-cell death, as well as better levels of insulin<br />
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<b>"I actually went down to the mouse house to see if the mice were getting diabetes," Shalev told The Birmingham News in 2012. When she found normal glucose levels, "We were dancing."</b></div><br />
In those studies, the group also revealed how verapamil lowers TXNIP — the decreased intracellular level of calcium ions caused by verapamil led to phosphorylation of the ChoRE binding protein that normally responds to glucose to control TXNIP transcription at the ChoRE. This phosphorylation prevented the binding protein from entering the beta-cell nucleus and interacting with the TXNIP gene. Shalev noted that these verapamil results identified, for the first time, “… an effective pharmacological means … to inhibit pancreatic beta-cell expression of proapoptotic TXNIP, enhance beta-cell survival and function, and thereby prevent and even improve overt diabetes and shed light on the mechanisms involved.”<br />
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<h3>Another Role for TXNIP, Another Drug Target?</h3><br />
<a href="http://www.ncbi.nlm.nih.gov/pubmed/23975026">In 2013,</a> TXNIP was shown to play another crucial role in beta-cell biology when the Shalev laboratory team discovered that high levels of TXNIP directly blocked insulin production in beta cells, acting through a newly identified pathway. TXNIP, they found, induced a microRNA called miR-204, which in turn down-regulated the MAFA transcription factor involved in promoting transcription of the insulin gene. <br />
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This means that miR-204 may offer another target for a future RNA drug, an area that is currently also being actively pursued by the Shalev lab. MicroRNAs, with 20 to 24 noncoding nucleotides, have rapidly gained prominence as regulators of gene expression in health and disease. Researchers are beginning to explore whether silencing targeted microRNAs may lead to a treatment for cancers or other diseases.<br />
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<h3>TXNIP's Vicious Cycle</h3><br />
<a href="http://www.ncbi.nlm.nih.gov/pubmed/24628418">This year Shalev reported</a> that TXNIP — surprisingly — can induce its own transcription. Her UAB research team found that TXNIP does this by affecting the same ChoRE binding protein (ChREBP) that was previously found to be key in the response to the drug verapamil. The researchers experimentally elevated TXNIP levels in beta cells and found this caused decreased phosphorylation of ChREBP, which led to its increased entry into the nucleus and its increased binding to the TXNIP promoter to boost transcription. This creates a harmful positive-feedback loop. <br />
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"These findings support the notion,” Shalev wrote in this 2014 paper, “that TXNIP levels rise over time, not only as a result of elevated blood glucose levels and/or endoplasmic reticulum stress, but also as part of a vicious cycle by which increased TXNIP levels lead to more TXNIP expression and thereby amplify the associated detrimental effects on beta-cell biology including oxidative stress, inflammation, and ultimately beta-cell death and disease progression.”<br />
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<h3>First Human Trial</h3><br />
<table cellpadding="0" cellspacing="0" class="tr-caption-container" style="float: right; margin-left: 1em; text-align: right;"><tbody>
<tr><td style="text-align: center;"><iframe allowfullscreen="1" frameborder="0" height="180" src="//www.youtube.com/embed/De1NCk3hhqw?rel=0&showinfo=0" style="float: right; margin: 15px;" width="320"></iframe> </td></tr>
<tr><td class="tr-caption" style="text-align: center;">Get a quick overview of the science behind UAB's verapamil <br />
trial in this animation</td></tr>
</tbody></table>The story doesn’t end here. Shalev’s long trail of laboratory research has now led to the <a href="http://www.uab.edu/news/innovation/item/5508">first human trial </a>to see if verapamil has an effect in patients who have developed type 1 diabetes within the previous three months. Adult volunteers, ages 19-45, will be treated with verapamil or a placebo for one year, as their insulin and blood glucose levels are continuously monitored. The three-year, $2.2 million trial will be conducted by the UAB Comprehensive Diabetes Center with funding from <a href="http://jdrf.org/">JDRF</a>, the largest charitable supporter of type 1 diabetes research.<br />
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Meanwhile, a UAB partnership with the <a href="http://www.southernresearch.org/">Southern Research Institute</a> — called the <a href="http://www.uab.edu/medicine/adda/">Alabama Drug Discovery Alliance</a> — is already working to develop small therapeutic molecules that mimic the diabetes-protecting effect produced by verapamil and inhibit TXNIP, but have a greater selectivity and efficacy. <a href="http://www.uab.edu/uabmagazine/features/discovery-channel">[Learn more about this work, and other high-potential projects in the Alabama Drug Discovery Alliance, in a new feature from UAB Magazine.]</a><br />
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So Shalev’s simple question — what gene in insulin-producing beta cells is most turned on by glucose? — has thus led the research out of her laboratory to possible new drugs, acting against a novel target to alleviate or reverse diabetes.<br />
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— <i><a href="mailto:jeffhans@uab.edu">Jeff Hansen</a></i><br />
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Unknownnoreply@blogger.com1tag:blogger.com,1999:blog-4162601566541462615.post-41522664381949754342014-10-28T10:51:00.001-07:002014-10-29T09:49:04.490-07:00Exploring new frontiers in personalized cancer care<div class="separator" style="clear: both; text-align: center;">
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<b>Personalized medicine is turning medical care on its head</b>, and cancer treatment is at the forefront of that revolution. The <a href="http://www3.ccc.uab.edu/">UAB Comprehensive Cancer Center</a>’s 17th Annual Research Retreat introduced this cutting-edge work to an audience of nearly 400 clinicians and researchers. The topic was timely after this summer’s announcement of major initiatives in genomics and personalized medicine at UAB, including a <a href="http://www.uab.edu/news/service/item/5109-hudsonalpha-and-uab-comprehensive-cancer-center-launch-consortium-announce-multiple-hires">research consortium between the Cancer Center and Huntsville’s HudsonAlpha Institute for Biotechnology</a>.<br />
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“Personalized medicine is the future of cancer care,” noted Eddy Yang, M.D., Ph.D., associate professor in the <a href="http://www.uab.edu/medicine/radonc/en/">UAB Department of Radiation Oncology</a>, who organized this year’s symposium. “This is certainly a glimpse of what is to come for the Cancer Center and UAB as a whole.”<br />
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The Future: Cancer as a Chronic Disease</h3>
“Oncology has been a first mover for personalized medicine,” said invited speaker Mark Boguski, M.D., Ph.D., founder of Genome Health Solutions and a faculty member at Harvard Medical School.<br />
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Boguski shared his remarkable vision. With the use of personalized medicine, he said, we can now begin to reimagine cancer as a manageable chronic disease. Subsequent speakers amplified that theme, describing advances, challenges and roadblocks to delivering personalized cancer care to patients across the United States.<br />
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Boguski began with three patient case histories.<br />
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The first was a patient in 2010 with adenocarcinoma that was EGFR-positive (that is, it contained mutations that activated the EGFR pathway). When treatment with the usual drug failed, genomic and transcriptomic analysis showed why — metastases from the original cancer were no longer EGFR-positive. But biomarkers on those cancer cells successfully identified a target for a different drug that was effective.<br />
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The second case was a metastatic squamous cell carcinoma. Genomic analysis showed, surprisingly, that it could be treated with a hematological cancer drug.<br />
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“You wouldn’t guess to use that on a solid tumor,” Boguski said.<br />
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Similarly, in a case of advanced lymphoblastic leukemia, genomic analysis unexpectedly pointed to using a renal cell carcinoma drug. With this sea change in the way that oncologists can make their treatment decisions, cancer patients are beginning to ask that their genomes be analyzed, Boguski said.<br />
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The UAB Cancer Center’s Molecular Tumor Board, initiated last year, identifies patients who could benefit from DNA sequencing of their tumors, said Yang. These tests, usually conducted in patients with rare tumors or tumors that do not respond to typical treatment, can identify off-label uses for cancer drugs. For example, BRAF inhibitors, which are approved for melanoma, have been used to treat patients with other tumor types that nevertheless harbor the BRAF V600E mutation, Yang said. In another important consideration, “treating physicians have been successful in getting third-party payers to pay for these drugs outside the ‘approved’ indications using the profiling results,” he explained.<br />
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Cancer Center Honors Research Excellence </h3>
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In addition to talks by leading investigators, the Cancer Center’s research retreat also features the work of a new generation of cancer researchers. Graduate students, postdoctoral fellows and junior faculty members took part in the annual poster competition; the 131 presentations emphasize the breadth of studies ongoing in the Cancer Center, from cancer prevention to bioinformatics. <a href="http://www3.ccc.uab.edu/index.php/newsroom/uab-cancer-center-honors-researchers-during-annual-retreat/">See the award winners here.</a></td> </tr>
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But roadblocks prevent the widespread delivery of such personalized, targeted care, Boguski noted in his talk, because:<br />
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•<span class="Apple-tab-span" style="white-space: pre;"> </span>80 percent of cancer care is delivered away from the top 50 cancer centers.<br />
•<span class="Apple-tab-span" style="white-space: pre;"> </span>Most doctors suffer from a knowledge gap; they need accelerated genome training to understand the top molecular biomarkers and how these markers can guide patient therapy.<br />
•<span class="Apple-tab-span" style="white-space: pre;"> </span>Pathologists — who are a key link to alter the delivery of care — need to know not only tissue pathology but also how to test for and report the molecular drivers of cancer.<br />
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Genomics Identifies Actionable Targets</h3>
Mark Kris, M.D., an attending physician at the Memorial Sloan Kettering Cancer Center and professor at the Weill Cornell Medical College, showed how genomics and personalized care can be harnessed to improve lung cancer survival.<br />
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Working with 11 cancer centers, Kris and colleagues tested 1,000 patients who had stage IV lung cancer. While tissue pathology confirmed adenocarcinoma, the cancers also underwent mutational analysis to probe for oncogenic drivers, and these findings were shared with physicians.<br />
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Two-thirds of the patients had at least one of 10 known oncogenic drivers. These drivers are “actionable targets” that helped to guide treatment choices, leading to increased median survival for these advanced cancer patients.<br />
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The French medical system, Kris noted, has provided genotyping to every lung cancer patient since 2011, at a rate of 20,000 patients a year. This equity of access to innovation does not exist in the United States, Kris said, even though the National Comprehensive Cancer Network clinical practice guidelines for non-small-cell lung cancer already list a set of molecular drivers that should be looked to to classify and guide treatment.<br />
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Needed: A New Kind of Trial</h3>
Another roadblock is the need for new ways to perform clinical trials of investigational drugs, said Donald Berry, Ph.D., professor of biostatistics at the M.D. Anderson Cancer Center and a co-founder of Berry Consultants.<br />
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Berry described how the use of Bayesian biostatistics in an adaptive platform trial can lower the numbers of patients needed for the trial, while simultaneously investigating multiple drugs and targets. He focused on a current study, I-SPY2, which is investigating treatments for breast cancer. (Berry noted that UAB is one of the largest contributors of patients to the trial.)<br />
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Data obtained during trials such as I-SPY2 are used to guide changes in the studies midstream, Berry explained. The result is nimble, lean studies that yield a more dependable estimate of the chance that a particular drug will succeed in its subsequent Phase III trial. Such information is crucial, given the cost and the failure rates of conventional Phase III trials.<br />
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Predicting Patient Response With Avatars</h3>
The final outside speaker, Paul Haluska Jr., M.D., Ph.D., associate professor of oncology at the Mayo Clinic, described an “Ovarian Avatar” model to personalize ovarian cancer treatment. The avatar is created by implanting live cancer tissue from the cancer patient into a mouse within two hours of surgery.<br />
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Haluska shared several definitions involved in this model:<br />
•<span class="Apple-tab-span" style="white-space: pre;"> </span>“Xenograft” is a tumor taken from one species and implanted in another;<br />
•<span class="Apple-tab-span" style="white-space: pre;"> </span>“Orthotopic” means the implant is placed in the natural body location for that type of tumor;<br />
•<span class="Apple-tab-span" style="white-space: pre;"> </span>“Patient-derived Xenograft” is a direct implant from the patient into the other species, without any intermediate in vitro growth or manipulation; and<br />
•<span class="Apple-tab-span" style="white-space: pre;"> </span> “Avatar” is thus an orthotopic, treatment-naïve, patient-derived xenograft.<br />
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Mayo implanted its first model in March 2010. Through this September, 404 models have been injected and 294 of them successfully engrafted. The avatar responses to a drug, Haluska said, appeared to mirror the patient responses to treatment with the same drug, and the avatars are being used for drug development.<br />
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The next step will be to actually use a particular patient’s avatar to direct her therapy. “It will be the first ovarian cancer with xenograft-directed therapy,” Haluska said. “The best predictor of response is response.”<br />
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Oncogenic Drivers and Racial Disparities</h3>
UAB has its own xenografts that are derived from glioblastoma multiforme tumors, said Christopher Willey, M.D., Ph.D., an associate professor in the Department of Radiation Oncology and director of the <a href="http://www.uab.edu/medicine/radonc/en/uabkinomecore">UAB Kinome Core </a>(pronounced “k-eye-nome”). But these personal avatars have a problem — they take too much time to establish compared to the rapid and fatal course of glioblastomas. So Willey hopes instead to use “kinomic” profiles of established avatars from other patients to guide the treatment for a new patient; glioblastoma tissue removed from the new patient during surgery can quickly be kinomically profiled.<br />
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Kinomics uses substrate arrays to identify which kinase enzymes — often found to be key oncogenic drivers — are active in the cancer cells. This can help select among about 30 cancer chemotherapeutic agents that target kinases.<br />
<br />
The other UAB speaker, Phillip Buckhaults, Ph.D., associate professor in the <a href="http://www.uab.edu/medicine/hemonc/">UAB Division of Hematology and Oncology</a>, described his search for genetic mechanisms that lead to earlier onset and higher incidence of breast and colon cancers in African-Americans, as compared to Caucasian-Americans. His trail began with the discovery of a point-mutant variant of the TP53 tumor suppressor gene in African-Americans, and it has led to the variant’s effect on the PRDM1 chromatin-silencing gene.<br />
<br />
Translating research insights from the laboratory to the clinic is a major focus of the UAB-HudsonAlpha cancer consortium, noted Cancer Center director Edward Partridge, M.D. “We’re not at the point yet where we can routinely apply genomics information from the tumor to treatment; but we’re clearly learning, and learning at a rapid pace,” Partridge said. “The goal of the consortium is to accelerate that, and we’re excited about what it means for the care we can bring to our patients.”<br />
<br />
— <i><a href="mailto:jhans@uab.edu">Jeff Hansen</a></i><br />
<br />Unknownnoreply@blogger.com0tag:blogger.com,1999:blog-4162601566541462615.post-37093109727194710862014-10-22T05:29:00.000-07:002014-10-22T05:29:21.787-07:00Hunting for clues to healthy aging, from the lab to the sea floor<table align="center" cellpadding="0" cellspacing="0" class="tr-caption-container" style="margin-left: auto; margin-right: auto; text-align: center;"><tbody>
<tr><td style="text-align: center;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgQ2tU1MgC2Q2VUiaX96gQnj2qNz_vAWdGXW7hsTkQjRFbiNcYTIgyVcIxhEIqBihRZ0H79S5RhcdlSihWLZEwFj3Y8HXqreYaGNYMGWDTGVBcoEX69GnVBrLHzwUlm8wNN-02_wcj62JVW/s1600/Steven_Austad_600.jpg" imageanchor="1" style="margin-left: auto; margin-right: auto;"><img border="0" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgQ2tU1MgC2Q2VUiaX96gQnj2qNz_vAWdGXW7hsTkQjRFbiNcYTIgyVcIxhEIqBihRZ0H79S5RhcdlSihWLZEwFj3Y8HXqreYaGNYMGWDTGVBcoEX69GnVBrLHzwUlm8wNN-02_wcj62JVW/s1600/Steven_Austad_600.jpg" /></a></td></tr>
<tr align="center"><td class="tr-caption">Researchers are "making an incredible amount of progress" in the search for molecular mechanisms underlying successful aging, says Steven Austad. His own studies are uncovering the secrets of long-lived animals, and investigating the anti-aging effects of the immunosuppressive drug rapamycin.</td></tr>
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<br />
<b>The longest-lived human on record</b> didn’t make it much past 120 years. That’s nothing compared to the ocean quahog, a fist-sized clam found off the coast of Maine. “They can live 500 years or longer,” said Steven Austad, Ph.D., chair of UAB’s <a href="http://www.uab.edu/cas/biology/">Department of Biology</a> and associate director of the <a href="http://www.uab.edu/medicine/aging/">UAB Comprehensive Center for Healthy Aging</a>. “They’ve been sitting out there on the sea floor since before Shakespeare was born.”<br />
<br />
Austad’s research focuses on understanding the underlying causes of aging at the molecular level. Although his studies take him in many fascinating directions, it’s the ancient clams that everyone remembers. “I’m known in the field as the guy who works with weird animals,” Austad said. <br />
<br />
So what do animals like the quahog know about healthy aging that we don’t? That question drives Austad’s studies in comparative gerontology, which look to long-lived animals to identify new molecular targets to help humans.<br />
<br />
<h4>
Protein Power</h4>
Clams — technically, bivalve mollusks — live longer than any other animal group; more than a dozen species have lifespans of a century or more. But they are not all masters of aging. Austad’s lab is studying mitochondrial function, protein stability and stress resistance across seven species of clams, with lifespans ranging from one year to the ocean quahog’s 500-plus years.<br />
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<table align="left" border="8" cellpadding="10" frame="hsides" style="margin-bottom: 20px; margin-right: 20px; width: 250px;"><tbody>
<tr> <td><span style="font-size: 14pt;"><b>Studying long-lived animals is “a way to quickly identify new genes that might be targets for new drugs to keep people healthy longer.”</b></span></td> </tr>
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Austad’s research has convinced him that one key to slowing aging is to protect the proteins inside our cells. “Proteins make everything work in the cell, and to do that, they have to be folded precisely like origami,” Austad said. “But as we get older they get battered about, and ultimately lose that precise shape.”<br />
<br />
That’s why Austad is so excited by what he’s found in ocean quahogs. “They keep their proteins in shape century after century,” he said. When Austad takes human proteins and adds them to a mix of tissues from the clams, “they become more stable, less likely to unfold.” His lab is now working to identify exactly what is protecting the clams’ proteins. That mechanism could point to a potential treatment for aging, along with new therapies for Alzheimer’s disease and other conditions caused by protein misfolding, Austad notes.<br />
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<h4>
Enter the Hydra</h4>
In addition to clams, Austad studies a tiny freshwater creature called a hydra, which is basically immortal. Or so scientists once thought, until they found one particular species of hydra that begins to age rapidly under the right combination of environmental conditions.<br />
<br />
“Under certain conditions, this hydra turns on a symphony of genes that prevent aging; under others, it does not,” Austad said. His lab is working to discover the molecular mechanisms that get switched on, or off, as the hydra’s environment changes. “These kinds of studies are a way to quickly identify new genes that might be targets for new drugs to keep people healthy longer,” Austad said.<br />
<br />
He adds that the opportunities for collaborative, translational work in the Comprehensive Center for Healthy Aging, which brings together a wide range of basic and applied scientists from schools across campus, helped draw him to UAB. <br />
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<h4>
Living Longer — and Better</h4>
This is a very exciting time to study aging, says Austad, who is in a position to survey the field as the scientific director for the American Federation for Aging Research. “We’re making an incredible amount of progress,” he said. “We know a lot of things from animal work that will slow aging by 20 percent, and that’s the difference between being healthy for 60 years and being healthy for over 70 years.”<br />
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<tr> <td><h3 style="text-align: center;">
Old Friends</h3>
Austad’s book <a href="http://www.amazon.com/Why-We-Age-Science-Discovering/dp/0471296465">“Why We Age,”</a> published in 1997 and since translated into eight languages, explained the latest aging research in layman’s terms. Ever since, “publishers have been after me to do an updated version,” he said. “But there are lots of books out there now on that topic.”<br />
<br />
Instead, he’s working on a book called “Methuselah’s Zoo,” which he described as “a natural history of successful aging.” It will include profiles of his favorite 500-year-old clams, but also 200-year-old whales and 40-year-old bats.</td> </tr>
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Living longer wouldn’t be much fun if you got progressively sicker, but “what we’re finding is that, if you treat the underlying causes of aging, you can push back cancer, heart disease, blindness, hearing loss — all of these diseases associated with aging,” said Austad.<br />
<br />
One particularly intriguing lead, being followed by Austad and other researchers worldwide, is the drug rapamycin, which is FDA-approved to prevent rejection after organ transplants. A series of studies, from yeast, worms and mice, have shown that rapamycin can extend lifespan as well.<br />
<br />
Rapamycin has “almost miraculous” effects against aging in mice, Austad says. “It prevents cancer, heart disease, Alzheimer’s — a whole host of things.” His lab is now working to understand how administering rapamycin at different points in an animal’s life affects the aging process.<br />
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<h4>
Curb Your Enthusiasm?</h4>
Despite these exciting findings, caution is required, Austad notes. “Nothing I have learned so far has changed my behavior,” he said. “I don’t take a bunch of pills; I’m not even tempted to take rapamycin at this point.” For one reason, rapamycin has several side effects in mouse studies, including an elevated incidence of cataracts, loss of glucose sensitivity and testicular atrophy. Austad believes that the right dosing and formulation could overcome these issues in humans, but “we still don’t know what the best dose is,” he said.<br />
<br />
At the moment, the best advice about healthy aging “is still the boring stuff your mother already told you,” Austad said. “‘Eat the right foods; don’t eat too much; exercise.’ But come back in 10 years and it will be a different answer.”<br />
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<tr> <td><h3 style="text-align: center;">
Biology’s Moment</h3>
The development of ever-better tools for investigating genes has brought about a revolution in biology, Austad says. He believes biology is set to dominate the 21st century the way that engineering and physics shaped the 20th — making vital contributions to everything from personalized medicine to climate change. And UAB’s Department of Biology will take a leading role in training, research and discovery in these areas, he adds.<br />
<br />
“The human world 50 years from now will be unrecognizable,” Austad said. “People never realized that they could go faster than a horse and suddenly they had airplanes. We haven’t had this fancy DNA technology for more than a decade and a half, and we’ve already come so far.” Learn more at <a href="http://www.uab.edu/cas/biology">www.uab.edu/cas/biology</a>.</td> </tr>
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Unknownnoreply@blogger.com0tag:blogger.com,1999:blog-4162601566541462615.post-26157223985696529042014-10-08T09:40:00.002-07:002014-10-08T09:40:29.897-07:00Wheel genuises: UAB team is teaching Army's self-driving trucks a new way to move<div class="separator" style="clear: both; text-align: center;">
<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEh4La1LiZx3lb7XTCKh9X4xowGQQKH7iVlcjewIqwsR5GHxta9zzP59YjtnvA0pkST1F1hYuAkf6mEgFaGy9jjqZ9tlwM73O35Psl3uctj0bu2uCo4SHCGPY0w_igXdwdMolFzIKHlcaBQe/s1600/truck_opening_image.jpg" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEh4La1LiZx3lb7XTCKh9X4xowGQQKH7iVlcjewIqwsR5GHxta9zzP59YjtnvA0pkST1F1hYuAkf6mEgFaGy9jjqZ9tlwM73O35Psl3uctj0bu2uCo4SHCGPY0w_igXdwdMolFzIKHlcaBQe/s1600/truck_opening_image.jpg" /></a></div>
<br />
Amazon got the world talking with its promise of aerial drone deliveries. Google is making progress toward its dream of a driverless car. But the U.S. Army has already surpassed the tech giants with an <a href="http://www.army.mil/article/128643/Second_Autonomous_Convoy_Demonstration_Completed_by_U_S__Army_TARDEC__Lockheed_Martin/">operational convoy of robot-driven trucks</a> capable of traveling up to 40 miles per hour.<br />
<br />
A self-driving convoy could deliver supplies without putting soldiers in harm’s way, or let those soldiers keep their eyes out for bandits instead of keeping them glued to the road. The Autonomous Mobility Appliquè System (AMAS), built for the Army’s <a href="http://www.army.mil/tardec">Tank Automotive Research, Development and Engineering Center</a> (TARDEC), has demonstrated its prowess in several online videos (see an example below).<br />
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<iframe allowfullscreen="" frameborder="0" height="315" src="//www.youtube.com/embed/HseUNLP6q24?rel=0" width="560"></iframe><br />
<br />
Now researchers in the <a href="http://www.uab.edu/engineering/home/">UAB School of Engineering </a>are working with TARDEC on an even more powerful unmanned system — one that will use smart tires, enhanced sensors and some very quick thinking to guide trucks safely over rough terrain.<br />
<br />
<h4>
Convoy!</h4>
<a href="http://www.uab.edu/engineering/home/departments-research/me/people/138-vvv">Vladimir Vantsevich, Sc.D., Ph.D., </a>professor in the <a href="http://www.uab.edu/engineering/home/departments-research/me">Department of Mechanical Engineering</a>, and director of the <a href="http://www.uab.edu/engineering/home/vrel">UAB Vehicle and Robotics Engineering Laboratory</a>, is an expert on the unique design challenges of multiwheeled vehicles. He has teamed up with UAB Ph.D. candidate Jeremy Gray, who is also a member of TARDEC’s Ground Vehicle Robotics group, on the unmanned convoy project.<br />
<br />
Teaching a six-wheeled, 18-ton truck to make smart driving decisions is one problem. String several more behind it, and the challenges multiply. “Imagine: no drivers, just five trucks, following the lead vehicle,” said Vantsevich. One issue is that, even though they are in a line, each vehicle is experiencing different terrain.<br />
<br />
“They’re following the same track, so each vehicle will compress the soil a little more, changing its physical properties,” Vantsevich said. “How do you redistribute power between the wheels to overcome this? If one gets stuck, how do you teach the others to avoid that obstacle? No one has ever done this before.”<br />
<br />
<h4>
Big Wheels Keep on Turning</h4>
In 2013, Vantsevich and Gray, along with TARDEC’s Jim Overholt, <a href="http://proceedings.asmedigitalcollection.asme.org/proceeding.aspx?articleid=1830710">presented an algorithm </a>that unmanned vehicles can use to react to changing ground conditions in real time. Putting that method into practice has required them to make several technical leaps.<br />
<br />
Compared to Google’s self-driving car, “an off-road vehicle requires much more information about its surroundings,” Vantsevich explained. A car driving on a highway will pretty much experience the same interaction between tire and asphalt throughout its trip, he says. “But a wheel going over off-road deformable terrain is experiencing continuous changes in its dynamics and motion.”<br />
<br />
The UAB researchers are dealing with this challenge by developing tires that read and react to their environment at unprecedented speeds — fast enough to respond to an obstacle while they are moving over it. “You have 60 milliseconds to understand what is going on with the tire, make a decision — should you change the torque of the tire, and in which direction? — and send a signal to the motor controlling that tire,” Vantsevich said.<br />
<br />
<h4>
At One With the Road</h4>
To accomplish this, the engineers are designing new types of high-speed sensors, and embedding them in the trucks’ tires and wheels. They are also devising ways to transmit this information from truck to truck, giving following trucks early warning about approaching hazards and terrain conditions.<br />
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<i>(Article continues beneath graphic)</i><br />
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjuLplDOQu_n6hT4rmrHR-guVJZrcjuFSvBKDH6_s-jTMPA-4MPkcNNrPbYSrA4jpLIL7Sf03_mP-eM2Sd-5e-Uljyssm6DgxxAm1bzFC0CXbzoQsEE_9iT50JvglPZ6Y1QrHvh2HZmDEQB/s1600/trucks_side_view_following.jpg" imageanchor="1" style="clear: left; float: left; margin-bottom: 1em; margin-right: 1em;"><img border="0" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjuLplDOQu_n6hT4rmrHR-guVJZrcjuFSvBKDH6_s-jTMPA-4MPkcNNrPbYSrA4jpLIL7Sf03_mP-eM2Sd-5e-Uljyssm6DgxxAm1bzFC0CXbzoQsEE_9iT50JvglPZ6Y1QrHvh2HZmDEQB/s1600/trucks_side_view_following.jpg" /></a><br />
<br />
<br />
Vantsevich declines to describe the new sensors and transmission methods in detail while patents are pending. He is no stranger to innovation, with 30 certified inventions related to the dynamics, energy and fuel efficiency of multiwheel-drive vehicles. In a related project, Vantsevich and Mostafa Salama, a Ph.D. candidate at UAB, are developing new control algorithms to boost fuel efficiency in unmanned vehicles by giving each wheel its own electronic brain.<br />
<br />
“I want my vehicle to be able to move from point A to point B with minimum power loss, and to do that I need to minimize the power loss that happens between each tire and the terrain,” said Salama. He has already adapted his original mathematical solution to this problem into a working prototype. Now he is refining that prototype in the Vehicle and Robotics Engineering Laboratory.<br />
<br />
These techniques could eventually let unmanned vehicles travel farther, and improve the efficiency of even conventional vehicles, Vantsevich notes. A 40-ton truck, for example, could improve efficiency up to 12 percent with this approach, he says. “That represents a huge fuel savings.”<br />
<br />
<h4>
Lessons From the Frontier</h4>
This summer, Vantsevich shared details from his unmanned convoy work with researchers from 15 nations at a NATO Advanced Study Institute (ASI) on “Advanced Autonomous Vehicle Design for Severe Environments” in Coventry, England. The ASI, supported by a NATO grant received by Vantsevich, was arranged and conducted with Coventry University and Sweden’s Royal Institute of Technology. Vantsevich is also the editor of two new series of books that explore hot topics in <a href="http://www.uab.edu/home/images/GROUNDVEHICLESERIES_Road-Terrain-Rail_2014.pdf">ground vehicle engineering </a>(Taylor & Francis, CRC Press) and <a href="http://www.uab.edu/home/images/RoboticsFLYER_2014.PDF">robotics engineering</a> (ASME Press).<br />
<br />
UAB students can learn the fundamentals of these new fields in <a href="http://www.uab.edu/engineering/home/departments-research/me/research/vehicle-engineering-a-robotics/courses">several courses</a> that Vantsevich has developed in the School of Engineering. Although they cover everything from robot design to innovative methods of power distribution, the courses have a unifying theme: mechatronics. This emerging discipline takes an interdisciplinary approach to engineering problems, acknowledging that today’s devices are a complex intermingling of mechanical, electrical and computer systems.<br />
<br />
Courses such as Systems Modeling and Controls, which Vantsevich taught to undergraduates in the spring 2014 semester, are all part of a mechatronics track that encompasses classes at the undergraduate and graduate levels, Vantsevich says. “We’re sharing our knowledge with a younger generation, and encourage them to work in these directions.”Unknownnoreply@blogger.com0tag:blogger.com,1999:blog-4162601566541462615.post-85607441028506950112014-10-01T12:04:00.001-07:002014-11-06T18:07:27.974-08:00Using magnets to find new drugs: Inside UAB's high-field nuclear magnetic resonance facility<div class="separator" style="clear: both; text-align: center;">
<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjgWPbZY8dJZLkJ2N0wPTH2FIHdIOMz7ULO7DG195HlbuVAwmIrAck9w4x6sFc_SKgk7Qwp_P4Kef8i25f-ID0ADmbsyqplmto0cStjmUalQ-4fBcYZnaNPNKdUpORU-SO16Jr43HhT4VTt/s1600/mix_nmr_shot.jpg" imageanchor="1"><img border="0" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjgWPbZY8dJZLkJ2N0wPTH2FIHdIOMz7ULO7DG195HlbuVAwmIrAck9w4x6sFc_SKgk7Qwp_P4Kef8i25f-ID0ADmbsyqplmto0cStjmUalQ-4fBcYZnaNPNKdUpORU-SO16Jr43HhT4VTt/s1600/mix_nmr_shot.jpg" /></a></div>
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<b>Most high-end lab equipment is inaccessible to the public eye</b>, but one of UAB's most powerful drug-discovery tools is clearly visible from the Campus Green. The <a href="http://www.uab.edu/research/administration/CentersCores/Pages/Cores.aspx?QueryTitle=HighFieldNMRCore">Central Alabama High Field Nuclear Magnetic Resonance Facility</a> occupies a gleaming ground-floor space in the Chemistry Building. Its massive magnets give researchers invaluable insight into disease-causing proteins — and the data they need to find new ways to stop them.<br />
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<img alt="UAB Magazine Fall 2014 cover" border="0" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgtCBO-dJzB69MVASVEFYqT8p2_ZtDOCkj2pgXFWb9FAZKjswSCZ1zAwGQgJYwtgzIn47pIi4UIOj4KPo5pUCsAOe-zqhHqaJyrovHklNckhe6DyOlFQeOkB63gLcR8GzSq4NlE6067DmlV/s1600/uabmag_cover_image.jpg" height="200" title="UAB Magazine Fall 2014 cover" width="150" /></div>
</td> </tr>
<tr> <td>The <a href="http://www.uab.edu/uabmagazine/features/discovery-channel">cover story</a> of the latest issue of <i>UAB Magazine</i> features the <a href="http://www.uab.edu/medicine/adda/">Alabama Drug Discovery Alliance</a>, a partnership between UAB and <a href="http://www.southernresearch.org/">Southern Research Institute </a>that aims to accelerate high-potential discoveries from the lab to patient-ready treatments. One key tool in that process is the Central Alabama High Field Nuclear Magnetic Resonance Facility, which opened in 2013. The Mix takes a closer look in this new feature.</td></tr>
</tbody></table>
<h4>
Spin This Way</h4>
Each of the facility's NMR machines specializes in a different type of job, but the basic functioning is the same, explains NMR director <a href="http://www.uab.edu/medicine/biochem/faculty-staff/primary-faculty-article/7-faculty-staff-content/faculty-staff-area/35-rama-krishna">N. Rama Krishna</a>, Ph.D., UAB professor in the <a href="http://www.uab.edu/medicine/biochem/">Department of Biochemistry and Molecular Genetics</a>. The machines generate strong magnetic fields that polarize the tiny magnets in the nuclei of hydrogen atoms. “Then, using radiofrequency pulses, you can count all of the individual hydrogen atoms in a sample, which tells you what amino acids are present and how they are arranged in space,” Krishna says. And that’s precisely the information you need to create a detailed picture of a protein’s structure.<br />
<br />
Mapping a protein's structure is crucial to understanding its function — and to finding ways to alter that function to treat disease. For instance, locating suitable "binding pockets" on a protein linked to brain cancer tells medicinal chemists how to design a drug to block (or enhance) that protein. "That's why NMR is one of the most versatile tools for drug-discovery research," Krishna says.<br />
<br />
The bigger your magnet, the better images you can get. The centerpiece of the NMR facility is an 850 MHz Bruker BioSpin model, one of the largest in the South, which allows scientists to analyze structural data on even the largest proteins.<br />
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<h4>
Building a Better Drug</h4>
The 850 MHz machine can also accelerate the drug-discovery process "by allowing researchers to rapidly test new compounds they've developed in the lab," Krishna adds. Using a technique called saturation transfer difference NMR (STD-NMR), Krishna and his team can register the minute changes in signals from hydrogen atoms that occur when a compound binds to a protein. It would be nearly impossible to capture this interaction directly, he points out, because "it may last only a few microseconds." With STD-NMR, researchers can screen a number of potential drugs at once, then focus on the ones that show signs of binding to the target protein.<br />
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<tr><td style="text-align: center;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgiMslRl2U0VNBejBPTj6AqZL6WQnVyLfEv311orcMNViZSOAj6yQtpe2sM-K2HWaW08NJ-PvMo2Mcvo5Za8J6xf416WFtaMKNk0MHJd7HBlK4pc1PLevWWx7MmTsBGEOZzk7y2Yy99s2sD/s1600/Pic5_Megapov.jpg" imageanchor="1" style="clear: right; margin-bottom: 1em; margin-left: auto; margin-right: auto;"><img border="0" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgiMslRl2U0VNBejBPTj6AqZL6WQnVyLfEv311orcMNViZSOAj6yQtpe2sM-K2HWaW08NJ-PvMo2Mcvo5Za8J6xf416WFtaMKNk0MHJd7HBlK4pc1PLevWWx7MmTsBGEOZzk7y2Yy99s2sD/s1600/Pic5_Megapov.jpg" height="240" width="320" /></a></td></tr>
<tr><td class="tr-caption" style="text-align: center;">UAB's Rama Krishna and scientists from Southern Research <br />
Institute have collaborated in developing a novel high-field <br />
NMR-based protocol for determining the binding of <br />
allosteric ligands to target proteins. They used the kinesin-5 <br />
protein Eg5 (a cancer target) and its inhibitor monastrol<br />
as an example (see above) for this protocol.</td></tr>
</tbody></table>
<br />
Using other techniques, researchers can analyze the disease-causing interaction between two proteins, and then find the right location to dock an inhibitor that would prevent the proteins from coming together. Or they could do the opposite, in an approach dubbed “fragment-based discovery” — using NMR data to identify two compounds that bind close together on a protein and “cross link” them to significantly improve their binding.<br />
<br />
Krishna uses these techniques in his own <a href="http://www.cancer.gov/">National Cancer Institute</a>-funded research to find new treatments for pancreatic cancer. Other UAB investigators are using the NMR facility to further their drug-discovery efforts in Parkinson's disease, brain tumors, breast cancer, heart disease, HIV and more. And as word of these capabilities has spread, researchers at institutions across the South have begun sending in samples to the NMR facility for evaluation.<br />
<br />
<h4>
Early Warning Signs</h4>
NMR is useful for many applications beyond drug discovery, Krishna adds. The facility's 600 MHz machine specializes in a hot area of medicine known as metabolomics, which studies the way the body processes everything from food to medicines.<br />
<br />
"If you are taking a drug that is toxic to the liver, the body will generate some small molecules — known as metabolites — associated with liver damage,” Krishna explains. "We can detect these molecules in the NMR spectra of biofluids such as urine and blood plasma and say, 'Aha, after this patient started taking the drug, we can see an increase in these signals, so something is going wrong." That can warn researchers of side effects from new drug treatments "long before there is any major problem," Krishna says.<br />
<br />
"The range of applications in this facility is amazing," adds Krishna. "It is a unique platform for everything from basic science to translational research.”<br />
<div>
<br /></div>
Unknownnoreply@blogger.com0tag:blogger.com,1999:blog-4162601566541462615.post-67151278753377531072014-09-22T08:46:00.000-07:002014-09-22T08:48:57.964-07:00Unique gene machine opens new pathways to personalized medicine<table align="center" cellpadding="0" cellspacing="0" class="tr-caption-container" style="margin-left: auto; margin-right: auto; text-align: center;"><tbody>
<tr><td style="text-align: center;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjNfgCnxHKW-Dvyw6JjoL-APRsDJSvzRJ2RO18zJK7o2Cs_OW4P_rIiFaCuhf5gr2wA9D7zmpMNHDljPY1RE5EmeqxxvYrd1T4IkTxl2Q3XdKIN94gKJ82EH4ydhfKq4ShT5zoHVuLG6Ijv/s1600/Eddy_Yang_600.jpg" imageanchor="1" style="margin-left: auto; margin-right: auto;"><img border="0" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjNfgCnxHKW-Dvyw6JjoL-APRsDJSvzRJ2RO18zJK7o2Cs_OW4P_rIiFaCuhf5gr2wA9D7zmpMNHDljPY1RE5EmeqxxvYrd1T4IkTxl2Q3XdKIN94gKJ82EH4ydhfKq4ShT5zoHVuLG6Ijv/s1600/Eddy_Yang_600.jpg" /></a></td></tr>
<tr><td class="tr-caption" style="text-align: center;">In the UAB Nanostring Laboratory, researchers such as Eddy Yang are taking advantage of the nCounter Analysis System's novel digital profiling technology to examine specific signaling pathways in cancer and other diseases. That work could lead to new insights to improve diagnosis and treatment decisions. </td></tr>
</tbody></table>
<br />
<b>Cancer is a devious enemy. </b>In lab tests, researchers have identified plenty of exciting genetic targets — weak links that should allow them to destroy tumors by halting production of a crucial enzyme, for example, or blocking a signal the cell needs to keep growing. All too often, however, these promising findings fizzle out in further testing.<br />
<br />
That is because cancer cells can take advantage of multiple, redundant signaling pathways to avoid areas that come under attack. “Tumor cells will just figure out a way to bypass them,” said Eddy Yang, M.D., Ph.D., an associate scientist in the<a href="http://www3.ccc.uab.edu/"> UAB Comprehensive Cancer Center</a> and associate professor in the <a href="http://www.uab.edu/medicine/radonc/en/">UAB Department of Radiation Oncology</a>.<br />
<br />
Mapping out the complex pathways involved in cancer and other diseases is a crucial step in finding better treatments — and identifying the best treatments for individual patients. If you know all the routes a tumor can use to evade attack, you can find therapies — or combinations of therapies — to block them all. Indeed, tracing cancer-related signaling pathways, and finding ways to use these insights to improve diagnosis and treatment decisions, is a major focus of research at the Cancer Center, Yang says. But spotting these pathways amid the information overload of a genomewide screening test can be extremely complex and time-consuming.<br />
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgpnwZmc3BeEzRn66t6kYiotZZlN8p4bGey40OTKg18DucGueA15jCFeGYsxrgj9AN4rRnOlWaDJd9DX7W45ZIPihv65vw_txuqyf__iMDVzDgP1UTtYnSzWsWqF0fhuvVy1063L9z0CR0o/s1600/_Eddy_Yang3_600.jpg" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgpnwZmc3BeEzRn66t6kYiotZZlN8p4bGey40OTKg18DucGueA15jCFeGYsxrgj9AN4rRnOlWaDJd9DX7W45ZIPihv65vw_txuqyf__iMDVzDgP1UTtYnSzWsWqF0fhuvVy1063L9z0CR0o/s1600/_Eddy_Yang3_600.jpg" height="212" width="320" /></a></div>
</td> </tr>
<tr> <td><b>nCounter: In Focus</b><br />
<ul>
<li>48-800 genes can be studied simultaneously</li>
<li>Applications include gene expression analysis, microRNA and lncRNA analysis, copy number variation analysis, ChIP-String analysis and leukemia fusion gene analysis</li>
<li>The system's novel digital technology is based on direct multiplexed quantification of nucleic acids; it provides highly reproducible data over 5 logs of dynamic range </li>
<li>Preconstructed panels include: PanCancer Pathways Panel, Human Kinase Panel, Human Immunology Panel, microRNA Panels, Cancer Copy Number Variation Assay</li>
<li>See the <a href="http://www.uab.edu/medicine/radonc/en/nanostring">UAB Nanostring Laboratory site </a>for more information and a schedule of fees and services</li>
</ul>
</td> </tr>
</tbody> </table>
<h4>
Targeting Crucial Pathways</h4>
Now, UAB researchers and clinicians have a new tool to investigate signaling pathways — and to translate their discoveries into clinic-ready diagnostic tests. The unique nCounter Analysis System, produced by Nanostring Laboratories, “is a platform to measure the expression of genes in a targeted manner,” Yang said. “Instead of looking at the whole genome, you can investigate anywhere from 48-800 genes at a time.” Researchers can zero in on certain pathways that they are studying, Yang explains, or they can use preset panels of previously identified cancer networks.<br />
<br />
Yang directs the new <a href="https://www.uab.edu/medicine/radonc/en/nanostring">UAB Nanostring Laboratory</a>, which is open to investigators across campus. He is using the nCounter to pursue his own research in experimental treatments for breast, prostate, and head and neck cancers. “I’m very interested in understanding the pathways that make a tumor tick,” Yang said. “I want to know which ones make it resistant to therapy and which ones could actually make it more sensitive to treatment.” With the nCounter, Yang said, “we can look from a 10,000-foot perspective rather than from sea level. It’s an exciting technology.”<br />
<br />
Another advantage of the nCounter is that, unlike other technologies, which may require whole molecules of high-quality RNA or amplification for analysis, the nCounter can gather information from small pieces of RNA. That means researchers can use it to look at pathways in tissue that is up to several decades old, retroactively verifying new patterns they have found instead of having to collect new samples for analysis. The nCounter can also perform a range of other tests, Yang says, including analysis of microRNAs, gene fusions and gene amplifications.<br />
<br />
<h4>
From Concept to Clinic</h4>
The nCounter is more than a research tool. It can run new diagnostic tests such as the ProSigna Assay, which gives clinicians an estimate of a patient’s likelihood of tumor recurrence based on which pathways are active in that patient. It is an excellent example of personalized medicine in action, Yang says. He envisions UAB researchers using the nCounter to develop novel tests to inform treatment decisions in cancer and other diseases. UAB is one of the first institutions nationwide with the ability to do both laboratory and clinical testing using the nCounter. <br />
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<table align="left" border="8" cellpadding="10" frame="hsides" style="margin-bottom: 20px; margin-right: 20px; width: 250px;"><tbody>
<tr> <td><span style="font-size: 14pt;"><b>“We hope to use the pattern of the pathway of genes to help guide therapy,” Yang said. “That’s the personalized medicine approach.”</b></span></td> </tr>
</tbody> </table>
<br />
Yang and collaborator Andres Forero, M.D., senior scientist at the UAB Cancer Center, will use the nCounter as part of a clinical trial testing a new treatment approach against triple-negative breast cancer. The trial, which recently began enrolling patients, is testing two different drugs — a PARP inhibitor and an EGFR inhibitor — to block two different pathways used by these tumors. <br />
<br />
“By blocking PARP, you block the ability of the tumors to repair DNA damage,” which should eventually result in cell death, Yang explains. But the tumors can take advantage of an alternate backup pathway to repair that damage, meaning PARP inhibitors alone are often ineffective. “By blocking EGFR, we will block that backup pathway,” Yang said. [To learn more about this study, call (205) 934-0309; visit the <a href="http://www3.ccc.uab.edu/index.php/why-choose-the-uab-comprehensive-cancer-center/clinical-trials/">Clinical Trials</a> section of the Comprehensive Cancer Center's website to see all current studies.] <br />
<br />
Using the nCounter, the researchers will compare the pathways altered in patients who respond to the therapy with those in patients who aren’t helped by the combination. In the future, that could let them identify the most appropriate patients for this treatment with a simple test. “We hope to use the pattern of the pathway of genes to help guide therapy,” Yang said. “That’s the personalized medicine approach.”Unknownnoreply@blogger.com0tag:blogger.com,1999:blog-4162601566541462615.post-2160356670720936322014-09-12T14:31:00.001-07:002014-09-12T14:31:59.273-07:00Grad student receives national award for new insight on alcohol and liver damage<table cellpadding="0" cellspacing="0" class="tr-caption-container" style="float: right; margin-left: 1em; text-align: right;"><tbody>
<tr><td style="text-align: center;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjOq13fAWkHicGYOCOqBuWN-QIrsrxb_Aspj-ljFk-OZk1z8FFQQy-enH2IrUL8-8xwQGJGH6zpnhmDzTQlbTQVcEA_rGm_ipPQmBX0rERMCIZpfJtb0XkdiIVimuzAwm6Y0FYyL4lc_i16/s1600/Uduak+Udoh+-headshot.jpg" imageanchor="1" style="clear: right; margin-bottom: 1em; margin-left: auto; margin-right: auto;"><img border="0" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjOq13fAWkHicGYOCOqBuWN-QIrsrxb_Aspj-ljFk-OZk1z8FFQQy-enH2IrUL8-8xwQGJGH6zpnhmDzTQlbTQVcEA_rGm_ipPQmBX0rERMCIZpfJtb0XkdiIVimuzAwm6Y0FYyL4lc_i16/s1600/Uduak+Udoh+-headshot.jpg" height="320" width="298" /></a></td></tr>
<tr><td class="tr-caption" style="text-align: center;">Uduak Udoh</td></tr>
</tbody></table>
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By connecting the dots between chronic drinking, molecular
clocks, and energy storage patterns, UAB doctoral student Uduak Udoh has
identified a potential new approach to target alcoholic liver disease. The work
has also earned her a top honor from the <a href="http://www.rsoa.org/">Research Society on Alcoholism</a> (RSA)
and the <a href="http://www.niaaa.nih.gov/">National Institute on Alcohol Abuse and Alcoholism</a> (NIAAA), and kudos
from former NIAAA director Enoch Gordis, M.D.<o:p></o:p></div>
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Udoh, a fifth-year doctoral student in <a href="http://www.uab.edu/gbs/pathobiology/">Pathobiology and Molecular Medicine</a>, received the Enoch Gordis Research Recognition Award during
the RSA's annual scientific meeting this summer. At the meeting, she presented
results from her dissertation project, "Hepatic Glycogen Metabolism Is
Impaired by Alcohol Consumption: Possible Role of the Liver Molecular
Clock."<o:p></o:p></div>
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Liver cells, like almost all human cells, have a built-in
circadian clock—a set of genes that control metabolism and other biological
processes in a daily cycle. Udoh's research shows that chronic alcohol
consumption disrupts the liver's normal pattern of creating glycogen, a storage
form of glucose.<o:p></o:p></div>
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"Glycogen in the liver is an important fuel reserve
that the body uses in between fasting and eating," explains Udoh, who is a
member of the lab of <a href="https://services.medicine.uab.edu/facultyDirectory/FacultyData.asp?s_org=392300000&vwAllfacultyPage=1&s_ApptType=Primary&FID=24148">Shannon Bailey, Ph.D., </a>in the <a href="http://www.uab.edu/medicine/pathology/divisions-a-sections/molecular-a-cellular">Division of Molecular and Cellular Pathology</a>. Previous research has shown that the liver clock controls
glycogen synthesis in a regular rhythm throughout the day. Emerging studies
show that alcohol can disrupt the liver clock's timing, just as it disturbs the
main circadian clock in the brain to disturb sleep and other behaviors.<o:p></o:p></div>
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Udoh's work connects these two observations. In mouse
models, "we normally see a nice diurnal rhythm to glycogen content in the
liver, which makes sense because metabolic needs vary throughout the day,"
Udoh says. But chronic alcohol consumption brings a significant change in that
pattern, and a corresponding decrease in glycogen levels, Udoh found. She also
demonstrated that alcohol disrupts signaling genes and proteins regulated by
the liver clock that control glycogen metabolism.<o:p></o:p></div>
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Without sufficient glycogen, the liver may lack the energy
to repair alcohol-generated damage, contributing to alcoholic liver disease.
Ultimately, Udoh's research "highlights the molecular clock as a novel
therapeutic target for alcoholic liver disease," says Bailey. (Learn more
about Bailey’s own research into <a href="http://themixuab.blogspot.com/2013/09/alcohol-throws-off-circadian-clock-to.html">chronic alcohol consumption and the liver clock in this Mix podcast</a>.)</div>
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Udoh's work was one of only six selected for presentation at
the Research Society on Alcoholism meeting from hundreds of applications.
Judges selected her for the Gordis award, which recognizes outstanding research
among graduate students and postdoctoral fellows, based on her oral
presentation and research poster session. One of the highlights of the event
was discussing her work with Dr. Gordis himself, Udoh says. "It's a great
honor."</div>
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<o:p></o:p></div>
Unknownnoreply@blogger.com0tag:blogger.com,1999:blog-4162601566541462615.post-64899874554280780732014-09-02T14:53:00.000-07:002014-09-02T14:53:22.992-07:00Using 3D printers and movie modeling techniques, UAB researchers enhance workplace safety devices<table align="center" cellpadding="0" cellspacing="0" class="tr-caption-container" style="margin-left: auto; margin-right: auto; text-align: center;"><tbody>
<tr><td style="text-align: center;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEizwsO-Ao3fe4VPk9azRBAnJO8JYiTNlWQb7-UZGLM2z0-a2XJCvPYXsFWFANe9hCi8dtkfsutNIQFNfP5_cjOo2CvwIL1JsSurf2xtXTWHi3Or_9DQhU6nS4SJZq-7JldAy_Be0NcAcnES/s1600/Claudiu_Lungu_RT600.jpg" imageanchor="1" style="margin-left: auto; margin-right: auto;"><img border="0" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEizwsO-Ao3fe4VPk9azRBAnJO8JYiTNlWQb7-UZGLM2z0-a2XJCvPYXsFWFANe9hCi8dtkfsutNIQFNfP5_cjOo2CvwIL1JsSurf2xtXTWHi3Or_9DQhU6nS4SJZq-7JldAy_Be0NcAcnES/s1600/Claudiu_Lungu_RT600.jpg" /></a></td></tr>
<tr><td class="tr-caption" style="text-align: center;">Claudiu Lungu and a team from UAB's Department of Environmental Health Sciences have devised a high-tech, low-cost method for designing and fabricating new respirator prototypes to improve workplace safety.</td></tr>
</tbody></table>
<br />
If you work on an auto painting crew, stir vats of artificial butter at a popcorn factory or handle asbestos at a shipyard, you are one of the 5 million American workers legally required to wear respiratory protective equipment on the job.<br />
<br />
But legal requirements and actual practice don't always match up. And even when workers wear their respirators, they may not be doing much good.<br />
<br />
Studies show that hundreds of thousands of workers—from 15 to 20 percent, according to recent research—may be wearing ill-fitting respirators, not designed for a workforce that has rapidly changed over the past decades.<br />
<br />
But a UAB research team has devised a high-tech, low-cost method for designing and fabricating new respirator prototypes to better match the variety of facial shapes in today's workplace. In addition to protecting industrial workers, the technology could aid members of the military as well. The findings are <a href="http://www.tandfonline.com/eprint/zV9TdEJKgR2aIwURkVjg/full#.U-t1WUiAZPY">published online</a> in the Journal of Occupational and Environmental Hygiene.<br />
<a name='more'></a><br />
<br />
<h4>
One Size Doesn't Fit All</h4>
"This is a big issue, because if something doesn't fit well, people won't wear it," says Claudiu T. Lungu, Ph.D., associate professor in the <a href="http://www.soph.uab.edu/ehs">Department of Environmental Health Sciences</a> in the <a href="http://www.soph.uab.edu/">UAB School of Public Health</a>, who is the corresponding author on the new paper. "They use it for awhile and then take it off." Even if the worker keeps the respirator on, "it's not like wearing it at all if you don't have a good fit," Lungu explains.<br />
<br />
All respirators currently on the market are based on facial anthropometric measurements of U.S. Air Force personnel taken in the 1960s — when the test subjects, like the U.S. workforce, were largely white and male. "The workforce has changed dramatically in the past 10 to 20 years," Lungu says. "We've definitely seen more women working in professions that had been typically occupied by men. We've also seen a rise in ethnic diversity in the workforce."<br />
<br />
Despite those changes, respirators today still "come in three sizes: small, medium and large," Lungu says. "Obviously human faces have greater variety than that."<br />
<br />
<table align="center" cellpadding="0" cellspacing="0" class="tr-caption-container" style="margin-left: auto; margin-right: auto; text-align: center;"><tbody>
<tr><td style="text-align: center;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhWCRFPpdQJ5dM3l4DFIszqnkdeDX_Sq74Jm85vhOcoSDOvN-6xqx75foQXtrCriwoes0qg8efECOhqiBG8XpR_ievGVf79YAmUSImUXzQDjGLEBf9UeJvg1CRClyIgN-qZutTXFJGZD6Km/s1600/Lungu_Mask_RT600.jpg" imageanchor="1" style="margin-left: auto; margin-right: auto;"><img border="0" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhWCRFPpdQJ5dM3l4DFIszqnkdeDX_Sq74Jm85vhOcoSDOvN-6xqx75foQXtrCriwoes0qg8efECOhqiBG8XpR_ievGVf79YAmUSImUXzQDjGLEBf9UeJvg1CRClyIgN-qZutTXFJGZD6Km/s1600/Lungu_Mask_RT600.jpg" /></a></td></tr>
<tr><td class="tr-caption" style="text-align: center;">The prototypes created by the UAB team will allow researchers to document the protective abilities of currently available respirators on various facial shapes—and test the protective prowess of new respirator models. </td></tr>
</tbody></table>
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<br />
<h4>
Face Off</h4>
In a 2007 study, the <a href="http://www.cdc.gov/niosh/">National Institute of Occupational Safety and Health</a> (NIOSH) took detailed measurements from both men and women, as well as members of different ethnic groups. "They discovered that about 15 to 20 percent of the working population is not fitted by any of the current respirators on the market," says Lungu.<br />
<br />
NIOSH's new "fit panel" includes two new sizes: short/wide and long/narrow. A 2010 NIOSH study provided digital headform models sized to correspond with the new fit panel for use in respirator design and testing. But several years later, these changes in respirator sizing have yet to reach the marketplace. This can be accounted for in part due to the fact that the only physical versions of the headforms available are a set of rigid plastic prototypes at Texas Tech University.<br />
<br />
One obstacle to wider adoption is the lack of research documenting a strong safety advantage for the new headform models. Without that data, manufacturers have little incentive to retool their production lines. That's where the UAB team came in.<br />
<br />
In a series of studies, Lungu and doctoral student Paula S. Joe, along with collaborators Phillip Shum and David Brown in the <a href="http://www.uab.edu/engineering/home/departments-research/me">Department of Mechanical Engineering</a>, have made important advances in the field.<br />
<br />
<h4>
Making a New Mask</h4>
In a 2012 paper, the UAB researchers demonstrated that a relatively low-tech laser scanner can take accurate measurements of the human face, replicating the current standard method of manual measurement at far lower cost than the expensive 3D scanners used by NIOSH.<br />
<br />
That same year, they used the plastic headform prototypes from Texas Tech to cast and mold silicone versions that much more accurately mimic the properties of human skin. Those silicone headforms allowed them to do preliminary fit testing on commercially available respirators.<br />
<br />
In the latest study, the UAB team used a CT scanner in the <a href="http://www.uab.edu/medicine/radiology/">UAB Department of Radiology</a>, a 3D printer in Atlanta, and mask-making techniques borrowed from Hollywood special effects teams to create a respirator to accommodate the Short/Wide headform.<br />
<br />
A CT scan of a currently available respirator facepiece gave the team the data to create their own version, sized to fit the image of the Short/Wide headform in a computer. They used the 3D printer to create a mold in hard plastic, then sculpted their respirator using silicone modeling techniques adapted from ones that Hollywood special effects artists use to create props for the movies.<br />
<br />
"The advantage of our method is that it's really inexpensive, a fraction of the cost of 3D printing respirators" directly in silicone, Lungu says. "Flexible materials are currently extremely expensive for 3D printing, but that's the future. The ideal would be to do very fast 3D scans of the human face and then 3D print respirators for each individual who needs one. Then again, it's not going to happen in the next 10 years, or even probably the next 20 years. In the meantime, the method we have developed has great potential."<br />
<br />
The next step for the UAB team is to fit-test their five custom-created headforms and respirator facepieces together. If the new facepieces perform better than currently available commercial respirators, the researchers plan to move forward with tests using a small sample of human participants.<br />
<br />
"The same techniques can be applied to creating helmets, eye protection and a wide range of other safety devices," Lungu adds.Unknownnoreply@blogger.com0tag:blogger.com,1999:blog-4162601566541462615.post-69289190798129442062014-08-28T09:19:00.000-07:002014-08-29T08:33:45.527-07:00Superfoods and breast cancer: Study takes a closer look at broccoli and green tea<div class="separator" style="clear: both; text-align: center;">
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<b>Could a combination of broccoli sprouts and green tea</b> offer protection against breast cancer — and transform hard-to-treat breast tumors into a type that responds to medication?<o:p></o:p></div>
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A series of studies in the lab of UAB <a href="http://www.uab.edu/cas/biology/">biologist </a>Trygve Tollefsbol, Ph.D., D.O., have generated encouraging findings. Tollefsbol, who is also a senior scientist in the <a href="http://www3.ccc.uab.edu/">UAB Comprehensive Cancer Center</a>, has shown that mice given sprouts in their chow and green tea polyphenols in their water are protected against tumor development. Intriguingly, he has also shown in animal studies that the combination can change estrogen receptor-negative (ER-) tumors, which have few treatment options, into estrogen receptor-positive (ER+) tumors, which can be treated with the anti-estrogen drug tamoxifen.<o:p></o:p></div>
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Now, Tollefsbol has received a $1.5-million, five-year grant from the National Institutes of Health to pinpoint the molecular mechanisms behind these effects. "We already have a lot of preliminary data showing that this combination works," Tollefsbol says. "The grant will allow us to extend that research and explore the effects genome-wide."<br />
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<h4>
Healthy Changes</h4>
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Tollefsbol's group hypothesizes that much of the cancer-fighting power of broccoli and green tea comes from epigenetic effects. Epigenetics focuses on the chemical markers surrounding genes, rather than the genes themselves. Because these markers affect the likelihood of a gene getting turned on or off, they play a crucial role in health and disease. (For a quick overview of epigenetics, see <a href="http://www.uab.edu/uabmagazine/2011/september/epigenetics/epigenetics-in-60-seconds">this infographic</a>.)<o:p></o:p></div>
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Cigarette smoke and the sun's UV rays, among other things, alter epigenetic markers in harmful ways. Studies in Tollefsbol's lab and elsewhere suggest that compounds in certain foods have positive epigenetic effects. (In fact, Tollefsbol made headlines in 2011 with a paper explaining the health effects of what he calls the <a href="http://www.uab.edu/news/latest/item/854-uab-biologists-show-how-veggies-work-in-cancer-fighting-diet">"epigenetics diet."</a>)<o:p></o:p></div>
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Two compounds that appear to be particularly effective against cancer are sulforaphane (found in vegetables such as broccoli, kale, and cabbage) and green tea polyphenols (found in green tea). Each works through a different epigenetic mechanism, Tollefsbol explains. Sulforaphane inhibits histone deacetylases; green tea polyphenols inhibit DNA methyltransferases. But these two mechanisms "often work together to control genes," Tollefsbol says.<o:p></o:p></div>
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<tr><td style="text-align: center;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjaHXWWuSI75jCQcHCY0NcFBDremk8mD89Jlsnve0Y42HRTPHSAblXaPcSC9sbHHDNqzBqcZnzeFA38jigCu81_PgkWF7-olDPGHCFdteAxbAaGGoQW-0sUQ-s9mMpd92zqv1VDtXuYP_C4/s1600/REV_superfood_graphic_Final.jpg" imageanchor="1" style="margin-left: auto; margin-right: auto;"><img border="0" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjaHXWWuSI75jCQcHCY0NcFBDremk8mD89Jlsnve0Y42HRTPHSAblXaPcSC9sbHHDNqzBqcZnzeFA38jigCu81_PgkWF7-olDPGHCFdteAxbAaGGoQW-0sUQ-s9mMpd92zqv1VDtXuYP_C4/s1600/REV_superfood_graphic_Final.jpg" /></a></td></tr>
<tr><td class="tr-caption" style="text-align: center;"><span style="background-color: white; color: #666666; font-family: 'Trebuchet MS', Trebuchet, Verdana, sans-serif; font-size: 11px; line-height: 14.7840003967285px;">UAB's Trygve Tollefsbol is exploring the hypothesis that broccoli and green tea help fight cancer by </span><br style="background-color: white; color: #666666; font-family: 'Trebuchet MS', Trebuchet, Verdana, sans-serif; font-size: 11px; line-height: 14.7840003967285px;" /><span style="background-color: white; color: #666666; font-family: 'Trebuchet MS', Trebuchet, Verdana, sans-serif; font-size: 11px; line-height: 14.7840003967285px;">working through different epigenetic mechanisms to inhibit cancer-causing genes and boost tumor-suppressor genes. </span></td></tr>
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That could explain why Tollefsbol's research has found that the combination of broccoli sprouts and green tea produces better effects than either compound alone. "The major problem with single agents is you have to consume too much," he says. Few people would be willing to drink a gallon of green tea every day, for example, and there is a limit to how much the body can absorb, anyway. "The idea is we need to find out what are the best combinations that will confer maximum protection."<o:p></o:p></div>
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In the current study, the researchers will use green tea polyphenols at the equivalent of about 2-3 cups per day of green tea consumed by humans and broccoli sprouts at the equivalent of about 1 cup per day in humans.<o:p></o:p></div>
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<h4>
Crucial Conversations</h4>
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<o:p></o:p></div>
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In order to analyze the cross-talk between different types of epigenetic changes, the UAB investigators had to invent a new technique. Chromatin immunoprecipitation-genomic bisulfite sequencing, which combines two individual tests, was developed in Tollefsbol's lab by Yuanyuan Li, Ph.D., currently an instructor in UAB's <a href="http://www.uab.edu/medicine/hemonc/">Division of Hematology and Oncology</a>.<o:p></o:p><br />
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<tr> <td><span style="font-size: 14pt;"><b>In the current study, the researchers will use green tea polyphenols at the equivalent of about 2-3 cups per day of green tea consumed by humans and broccoli sprouts at the equivalent of about 1 cup per day in humans.</b></span></td> </tr>
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This novel technique will allow the scientists to examine how their dietary combination affects tumor suppressor genes such as p16, for example, or the enzyme telomerase, which cancer cells need to keep up their endless cell division. (Learn more about how telomerase fuels cancer, and fights aging, in this <a href="http://themixuab.blogspot.com/2014/08/the-immortality-enzyme-telomerase.html">related article</a>.)<o:p></o:p></div>
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"It is also important for us to understand the global profile of the epigenetic effects of these compounds, and what other genes they may be impacting," Tollefsbol says. To do that, his lab is collaborating with UAB's <a href="http://www.uab.edu/hcgs/genomics-core-lab">Heflin Center for Genomic Science </a>to analyze changes in DNA methylation and histone modifications across the genome in response to green tea polyphenols and broccoli sprouts.<o:p></o:p></div>
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<h4>
From ER- to ER+</h4>
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<o:p></o:p></div>
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Tollefsbol is particularly excited to follow up on a surprising finding his lab made a few years ago. The broccoli-green tea combination, they found, can transform ER- tumors to ER+ tumors in mouse models. "We were very happy to see that," Tollefsbol says, "because estrogen receptor-negative tumors are a major problem."<o:p></o:p></div>
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Tollefsbol's group has since shown that sulforaphane, combined with a compound in green tea called epigallocatechin-3-gallate, "leads to reactivation of the estrogen receptor alpha gene" in ER- tumor cells, which allows them to be targeted by tamoxifen.<o:p></o:p></div>
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With the NIH grant, Tollefsbol will expand that discovery by looking at the combination's effects in two major subtypes of ER- tumors: SV40 and HER2/neu. "We think this has a tremendous amount of potential," Tollefsbol says. "These observations may lead to novel chemoprevention approaches for women at high risk of developing ER- breast cancer who have few other options."</div>
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Tollefsbol's team also hopes to find epigenetic biomarkers of ER- breast cancer. "There's a lot of interest in this area," he says. "At that point, you could predict if a person is predisposed to cancer. You could also use that information to monitor treatment as well. A doctor could look at epigenetic changes in the genome to see if they are normalizing in response to the drugs."<o:p></o:p></div>
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Learn More</h4>
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Get a quick overview of epigenetics in this video from<i> UAB Magazine</i>.<br />
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<iframe allowfullscreen="" frameborder="0" height="281" mozallowfullscreen="" src="//player.vimeo.com/video/43210937?byline=0&portrait=0" webkitallowfullscreen="" width="500"></iframe><br /></div>
Unknownnoreply@blogger.com2tag:blogger.com,1999:blog-4162601566541462615.post-40543699693240839412014-08-28T09:16:00.007-07:002014-09-02T15:26:37.160-07:00The immortality enzyme? Telomerase fights aging, fuels cancer<div class="MsoNormal">
In a lab in the heart of Campbell Hall, UAB <a href="http://www.uab.edu/cas/biology/">biologist </a>Trygve
Tollefsbol, Ph.D., D.O., stores the secret to immortality—but you may not want it.<o:p></o:p></div>
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<tr><td style="text-align: center;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEirRnQ0vRF507MaOuR5ACM1BF-tkARgzR8RIuXZLGJqZSP7jwYJnXHN4TLjnCj4IAzFQGLMXvYUU7oWCzAdPpmB3SWfXp5GN2067fTByODq1srlnQ-b1Mz7BKCc7AzX06MqfYp8im14Mc91/s1600/Tollefsbol_700.jpg" imageanchor="1" style="clear: right; margin-bottom: 1em; margin-left: auto; margin-right: auto;"><img border="0" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEirRnQ0vRF507MaOuR5ACM1BF-tkARgzR8RIuXZLGJqZSP7jwYJnXHN4TLjnCj4IAzFQGLMXvYUU7oWCzAdPpmB3SWfXp5GN2067fTByODq1srlnQ-b1Mz7BKCc7AzX06MqfYp8im14Mc91/s1600/Tollefsbol_700.jpg" height="266" width="400" /></a></td></tr>
<tr><td class="tr-caption" style="text-align: center;">Trygve Tollefsbol is a renowned expert on telomerase, an enzyme that<br />
plays crucial roles in determining our lifespans and fueling cancer growth.</td></tr>
</tbody></table>
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Telomerase, the enzyme in question, is a quirky character.
Even though it is dormant most of the time, it appears to play a key role in
all three of Tollefsbol’s main research interests: aging, cancer, and
epigenetics.<o:p></o:p></div>
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Telomerase’s job is to lengthen telomeres, little caps at
the end of our chromosomes that keep the chromosomes from becoming unstable
during cell division. (They’re kind of like the plastic cylinders on the ends
of shoelaces, Tollefsbol says.) But a little bit gets shaved off with each cycle
of division. Eventually, there is very little protective telomere left, and
cells age and stop dividing.<br />
<a name='more'></a><o:p></o:p></div>
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<h4>
Immortal Cells—With a Twist</h4>
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“We can make cells live forever in our lab by giving them
telomerase,” Tollefsbol says. But don’t book your next 200 vacations just yet.
“Being able to do things at a cellular level and for a whole organism are two
entirely different things,” Tollefsbol cautions. His lab continues to
investigate telomerase as a potential way to extend lifespans. But strangely
enough, they’re working to eliminate telomerase as well.<o:p></o:p></div>
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There’s a wrinkle in the telomerase story: “Most cancer
cells are addicted to it,” says Tollefsbol, who is a senior scientist in the <a href="http://www3.ccc.uab.edu/">UAB Comprehensive Cancer Center</a>. “They have to have their telomeres
maintained to keep replicating. Telomerase doesn’t cause cancer itself, but most
cancer cells can’t be cancer cells without telomerase.” That’s what allows them
to keep growing. </div>
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In fact, 90 percent of cancers are fueled by telomerase,
Tollefsbol explains. “And the more malignant the cancer, the higher the
telomerase expression. Some people believe that aging is just a
tumor-suppression mechanism—we down-regulate telomerase so we will not be as
susceptible to cancer.”<o:p></o:p></div>
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Several research groups, including Tollefsbol’s, are trying
to find ways to selectively target the telomerase in cancer cells. (He recently
co-edited a <a href="http://www.amazon.com/Telomerase-Inhibition-Strategies-Protocols-Molecular/dp/1588296830/ref=sr_1_1?ie=UTF8&qid=1407771437&sr=8-1&keywords=telomerase+inhibition">book on the topic</a> with his wife, UAB researcher Lucy Andrews, Ph.D.)
His team has had some success in inserting “RNA interference” sequences into
telomerase genes that tag the enzyme for destruction by the cell’s repair
mechanisms. </div>
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They are also looking into the process that allows normal cells to
turn telomerase back on. But Tollefsbol is also exploring ways to “get ahead of
the curve”; that is, to prevent the tumors from forming in the first place.<o:p></o:p></div>
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<h4>
Food Finds</h4>
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<o:p></o:p></div>
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Tollefsbol is particularly interested in sulforaphane—“a
major active component of cruciferous vegetables” such as broccoli, cabbage,
cauliflower, and kale—and green tea polyphenols. “We’ve discovered that many of
these dietary compounds can prevent the telomerase gene from being activated,”
Tollefsbol says. “We’re very excited about this, because it suggests that if
one eats the right diet during their life that they may be able to keep
telomerase from becoming active, which would lower the risk of cells becoming
cancer cells.”<br />
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These compounds seem to control telomerase through
epigenetic means—that is, by altering the chemical markers on the telomerase
gene to stop the enzyme from being produced. (In the late 1990s, Tollefsbol and
Andrews were the first to propose that telomerase is under epigenetic control,
publishing their hypothesis in a theoretical journal. “We were right, fortunately,”
he says.)<o:p></o:p></div>
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Tollefsbol recently received a $1.5-million grant from the
National Institutes of Health to investigate the <a href="http://themixuab.blogspot.com/2014/08/superfoods-and-breast-cancer-study.html">cancer-fighting effects </a>of a combination of broccoli
sprouts and green tea polyphenols. <o:p></o:p></div>
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Tollefsbol says his lab has already worked out what appear
to be the optimal concentrations of these foods in a diet. For green tea,
“generally it’s about two to five cups per day, depending on the size of the
person,” Tollefsbol says. For the cruciferous vegetables, “it’s about a cup a
day,” he says. “It seems that this could be incorporated worldwide and affect
hundreds of thousands, if not millions, of people.”<o:p></o:p></div>
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What if you don’t like broccoli? “Usually what I recommend
is using some low-calorie sauce, such as soy sauce, to make it taste better,”
he says. And it’s better to eat the whole food than take a supplement, he
notes. “We find that whole foods tend to be much more effective, because
there’s a synergy between the many different compounds in the whole foods.”<o:p></o:p></div>
Unknownnoreply@blogger.com0tag:blogger.com,1999:blog-4162601566541462615.post-87880219963973605372014-08-13T06:16:00.000-07:002014-08-13T06:17:57.379-07:00Truth and consequences: Building a game to fight the rural HIV epidemic<div style="text-align: right;">
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<table align="center" cellpadding="0" cellspacing="0" class="tr-caption-container" style="margin-left: auto; margin-right: auto; text-align: center;"><tbody>
<tr><td style="text-align: center;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgE2AJvb1DF0t3xFspAfoGb3bSCWi00glYPSpUR1KDEHTkRU2wpYuW8gy2NtkTlw_K9AYon9kKrSNSqNgx_ud38dP7Lv2WRCtNG5UEJiTpUBcJFLXTDvJ3-7Tz9rkwSfT-Yvl9lWSMBX03l/s1600/mix-screen7.jpg" imageanchor="1" style="margin-left: auto; margin-right: auto;"><img border="0" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgE2AJvb1DF0t3xFspAfoGb3bSCWi00glYPSpUR1KDEHTkRU2wpYuW8gy2NtkTlw_K9AYon9kKrSNSqNgx_ud38dP7Lv2WRCtNG5UEJiTpUBcJFLXTDvJ3-7Tz9rkwSfT-Yvl9lWSMBX03l/s1600/mix-screen7.jpg" /></a></td></tr>
<tr><td class="tr-caption" style="text-align: center;">UAB researcher Comfort Enah is developing a video game to help high-risk teens and pre-teens<br />
learn vital lessons about HIV prevention. An early graphic concept is shown above.</td></tr>
</tbody></table>
<br />
<br />
<b>Comfort Enah, Ph.D., a researcher in the<a href="http://www.uab.edu/nursing/home/"> UAB School of Nursing</a>, can't build a time machine to help teens avoid making bad decisions in the future. So she's creating the next best thing: a video game.</b><br />
<br />
Working with a team from the <a href="http://www.uab.edu/engineering/home/">School of Engineering</a>, Enah is crafting a simulation of the challenges of modern teen life—including social media shaming, drug and alcohol use, dating boundaries, and the wildfire spread of misinformation on the Internet. The goal is to slow the HIV epidemic among adolescents in the rural South. Enah's dream, if the game proves effective, is to take it to the even more hard-hit communities <span style="text-align: center;">of sub-Saharan Africa, where she grew up.</span><br />
<span style="text-align: center;"><br /></span>
<br />
<h4>
Maturity without Maturity</h4>
Over the past century, puberty has been arriving earlier and earlier, which means that “teens are spending longer and longer periods with bodies that are sexually mature and brains that aren't yet capable of anticipating the long-term consequences of their actions,” says Enah, an assistant professor in the Department of Nursing Community Health Outcomes. “They need to practice their responses to those risky situations, and games are a way to do that in private and as often as necessary.”<br />
<a name='more'></a><br />
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<table cellpadding="0" cellspacing="0" class="tr-caption-container" style="float: right; margin-left: 1em; text-align: right;"><tbody>
<tr><td style="text-align: center;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgyla1EWqcaKTSl1i3w-jznpKSOcbIRP_YR-Er-AYSmt6IXxFu40m_9rJ28Tq96_O5H8M1dt1gNVSwVNDHypqqHsMK0MmwNusigSuNgFW7bgfTxodKOp6S-F07wp33HdiJNk3LPgLl2t9Ca/s1600/comfort_enah_300.jpg" imageanchor="1" style="clear: right; margin-bottom: 1em; margin-left: auto; margin-right: auto;"><img border="0" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgyla1EWqcaKTSl1i3w-jznpKSOcbIRP_YR-Er-AYSmt6IXxFu40m_9rJ28Tq96_O5H8M1dt1gNVSwVNDHypqqHsMK0MmwNusigSuNgFW7bgfTxodKOp6S-F07wp33HdiJNk3LPgLl2t9Ca/s1600/comfort_enah_300.jpg" height="320" width="222" /></a></td></tr>
<tr><td class="tr-caption" style="text-align: center;">"No one wants to play an 'HIV prevention<br />
game,'" says Enah (above). "We have to embed the<br />
messages as part of the play experience itself." </td></tr>
</tbody></table>
Enah wants to create a safe space in cyberspace—an adventure game that gives high-risk teens and pre-teens the chance to rehearse the challenges they'll face—and visualize the results of their choices decades down the line. The project is funded by a grant from the <a href="http://www.ninr.nih.gov/">National Institute of Nursing Research</a>.<br />
<br />
To succeed, her game can't be lame. “No one wants to play an 'HIV prevention game,'” Enah says. “We have to embed the messages as part of the play experience itself.” She has teamed up with the School of Engineering's <a href="http://etlab.eng.uab.edu/etlab/">Enabling Technology Lab</a>, which has programmers capable of building a game with the industry-standard Unity software, and an artist with the skill to make it come alive. Enah has also recruited a crew of hard-to-please beta-testers: dozens of adolescents living in Alabama's Black Belt, which has been hit hard by HIV.<br />
<br />
<h4>
Left Behind</h4>
The South as a whole accounts for 45 percent of new cases of HIV/AIDS in the United States and nearly half of all HIV/AIDS deaths. Black teens are particularly vulnerable; they make up only 17 percent of the American adolescent population, but accounted for 68 percent of new AIDS diagnoses among that group in 2009.<br />
<br />
Most research and HIV education efforts aimed at teens have focused on urban areas, Enah says, while rural youths have received little attention. She and colleagues addressed that with a paper in the Journal of Psychosocial Nursing in February 2014, in which they documented a mix of stigma, denial, and misconceptions among teens in several counties in Alabama's Black Belt region. “Participants said things like, 'People just need to know if you take an antibiotic [against HIV] you'll be fine,'“ Enah says. Nearly half of the participants mistakenly thought that a vaccine for HIV is available.<br />
<br />
But the biggest problem may be one these teens share with their fellow adolescents around the world: “They just really don't think they are at risk,” Enah says. “They think it is somebody else's problem.” Traditional public health HIV education programs haven't been very effective with teens, Enah points out. “For six months maybe you get some effect, but you quickly lose their interest,” she says.<br />
<br />
<h4>
SimTeen </h4>
<table cellpadding="0" cellspacing="0" class="tr-caption-container" style="float: right; margin-left: 1em; text-align: right;"><tbody>
<tr><td style="text-align: center;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhIf5aFD8gOsSjF5DmfM_zDBOhTUi0qRP0946TVQqEnpNdZVRNeyu94HSI_DYHj09lZUDM9jDau184r-Efy9EeyKqZDH7f7GS9i2k4_Y5WnMDKFcfaPDKXQGVobAC_FEbwnp8I_BKFMg7bY/s1600/screen3.jpg" imageanchor="1" style="clear: right; margin-bottom: 1em; margin-left: auto; margin-right: auto;"><img border="0" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhIf5aFD8gOsSjF5DmfM_zDBOhTUi0qRP0946TVQqEnpNdZVRNeyu94HSI_DYHj09lZUDM9jDau184r-Efy9EeyKqZDH7f7GS9i2k4_Y5WnMDKFcfaPDKXQGVobAC_FEbwnp8I_BKFMg7bY/s1600/screen3.jpg" height="179" width="320" /></a></td></tr>
<tr><td class="tr-caption" style="text-align: center;">More early graphic concepts from the storyboards<br />
created by Enah and the design team at UAB's<br />
Enabling Technology Lab.</td></tr>
</tbody></table>
So Enah is taking an alternative path. In a series of meetings in towns across the Black Belt, she has gathered evidence that a game-based intervention could hold the interest of rural teens. She found that video games are a popular outlet for youths who have few other entertainment options, and that most have access to computers and gaming systems. Enah is using the feedback from these focus groups to design the first draft of the game. When that’s ready, she'll take it to her testers and let them tear it apart, then redesign the game based on their criticisms, and so on.<br />
<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhRzunfrJhKfa5O407PBehfUfYHZzTIpW9GHjS3mvQloKfV0FYgR_nMP5IedPoIYLA6Rv3C6OWEP4NxLKkqIPrVEpikeKnC9kFEKyZEojnphu9iSQb4JOQFTETr4ZVqCI2KY5qZgxAgxQCq/s1600/screen6.jpg" imageanchor="1" style="clear: right; float: right; margin-bottom: 1em; margin-left: 1em;"><img border="0" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhRzunfrJhKfa5O407PBehfUfYHZzTIpW9GHjS3mvQloKfV0FYgR_nMP5IedPoIYLA6Rv3C6OWEP4NxLKkqIPrVEpikeKnC9kFEKyZEojnphu9iSQb4JOQFTETr4ZVqCI2KY5qZgxAgxQCq/s1600/screen6.jpg" height="179" width="320" /></a><br />
The game's content will be “embedded in a series of challenges,” Enah says. “For example, you'll face a situation where you are with somebody who is desirable—at a football game behind the bleachers—and they want to go further than you want to go,” Enah says. “How do you handle that?”<br />
<br />
<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEht-N2dBaOQ5aHIXPNpWZmzPHZu1RxzY_jzMN4uBdp7-I4QG21Kc6tfn5rSMEak2X7Fzad6BD5UKlbRbvpuNGHSCYt-_RXw_glu2Sr4LMa8Wnb7pqG_V1TfHujw3cXJTNCIytRQrfv8U0n2/s1600/screen4.jpg" imageanchor="1" style="clear: right; float: right; margin-bottom: 1em; margin-left: 1em;"><img border="0" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEht-N2dBaOQ5aHIXPNpWZmzPHZu1RxzY_jzMN4uBdp7-I4QG21Kc6tfn5rSMEak2X7Fzad6BD5UKlbRbvpuNGHSCYt-_RXw_glu2Sr4LMa8Wnb7pqG_V1TfHujw3cXJTNCIytRQrfv8U0n2/s1600/screen4.jpg" height="179" style="cursor: move;" width="320" /></a>Players will have a range of options to choose, “and the game will keep track of their decision-making,” says Enah. “All of this will add up. If they are mostly risky with their choices, then their outcome is not going to look that great.”<br />
<br />
<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEi6-HynztQv8ltpqrjcJOlaaWZtGJHo_BnsdNt_p3xjyE3ex4NaDFQfs1tgU8aPNE50EJ4SqFjnSqPq4FMeil6Gng-Ay6zEJ6qY-YSrP9SAr4px6nnP4wsIppaoTYB5A41dE1rOycPW2BRB/s1600/screen5.jpg" imageanchor="1" style="clear: right; float: right; margin-bottom: 1em; margin-left: 1em;"><img border="0" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEi6-HynztQv8ltpqrjcJOlaaWZtGJHo_BnsdNt_p3xjyE3ex4NaDFQfs1tgU8aPNE50EJ4SqFjnSqPq4FMeil6Gng-Ay6zEJ6qY-YSrP9SAr4px6nnP4wsIppaoTYB5A41dE1rOycPW2BRB/s1600/screen5.jpg" height="179" width="320" /></a>Periodically, players will “get to peek into the future and see the impact of all these little daily decisions on their lives; mostly on their health, but also on their success in life,” says Enah. “Cognitive research has demonstrated that teenage brains aren't fully capable of evaluating the risks of a situation,” she notes. “We want to show them the consequences so they realize that health and success in life go together.”<br />
<br />
The game will be tailored to the player, Enah adds. A 12-year-old girl who is sexually inexperienced will receive different messages than a 16-year-old boy who is sexually experienced, for example.<br />
<br />
<h4>
<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhXiuAfdXIZeNopSnlkMhmPsxR051I1ge2FioVT4i9d_GPRx63CBdi92JKO0lnNM_35kHllZ3r6M0SQRdtvgWtRAzPH01Vg3ocgcBJDPVA9eCyZIRRs4t84VTDrHOCmhlmkk1psugDlgZBK/s1600/screen8.jpg" imageanchor="1" style="clear: right; float: right; margin-bottom: 1em; margin-left: 1em;"><img border="0" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhXiuAfdXIZeNopSnlkMhmPsxR051I1ge2FioVT4i9d_GPRx63CBdi92JKO0lnNM_35kHllZ3r6M0SQRdtvgWtRAzPH01Vg3ocgcBJDPVA9eCyZIRRs4t84VTDrHOCmhlmkk1psugDlgZBK/s1600/screen8.jpg" height="179" width="320" /></a>Peer Pressures</h4>
The game will also help players evaluate peer advice, both good and bad. Based on her own research and many other studies, “it is clear that peer norms—or your perception of peer norms—are one of the biggest drivers of whether kids engage in risk behaviors or not,” Enah says. “We really want to tackle that.”<br />
<br />
At the game's decision points, players will often “get input from their peers,” Enah explains. “Some of those peers will give them advice that is safer for their health, others will offer opinions that are very risky. The players get to decide what to do based on all that they have heard.”<br />
<br />
Players will also have the chance to correct misinformation they get from their peers—to explain that antibiotics in fact have no effect on HIV and that there is no vaccine to cure AIDS. “If they don't have that information, we are going to give them the option of seeking out a mentor in the game,” Enah says.<br />
<br />
<h4>
International Appeal</h4>
If the game is successful, Enah hopes to expand her model overseas. “I come from sub-Saharan Africa, and there's a big need there, so I always have that in the back of my mind,” she says. The millions suffering from HIV “aren't just numbers to me. I have classmates, cousins, neighbors that have died from this disease. And from a very early age, I felt an obligation to help. ‘If we can prevent this disease,’ I thought, ‘why aren't we doing more?’”<br />
<br />
Exporting the game would require some cultural tweaks—swapping a football game scenario for a soccer match, for instance—but the UAB team is purposely designing the game to be as flexible as possible. “In Africa, many people don't have computers, but everyone has a mobile phone,” Enah says. “We would have to build the game around a phone interface. We would also have to change some of the wording and situations, but the mechanics of the game could stay the same.”<br />
<br />
The ultimate message for players, wherever they live, “is that what you do now has implications for your future,” Enah says. “We're telling them, 'Yes, there are limitations in your environment, there are things you may not have control over, but there are some things you can control, some decisions you can make that might enhance your potential for success in the future.'“<br />
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Unknownnoreply@blogger.com1tag:blogger.com,1999:blog-4162601566541462615.post-31570531910057195982014-07-29T08:18:00.000-07:002014-07-30T09:23:19.383-07:00How do mom's microbes affect pregnancy outcomes? UAB research aims to find out<div class="separator" style="clear: both; text-align: center;">
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<br />
As a baby slides out of the birth canal, on the way to its first breath, its body becomes coated in its mother’s microbes. This first interaction with outside organisms could be key to shaping the development of the baby’s immune system.<br />
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Our microbes, collectively called the microbiome, most often live in harmony with our bodies. They support the immune system, help to digest food and keep the metabolism on track, and fight off disease-causing bacteria. But researchers suspect that mom’s microbiome could play a role in when her children are born, and what happens to them as they grow. <br />
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“Most people know about the microbes that colonize the gut,” says Rodney Edwards, M.D., an associate professor in UAB’s <a href="http://www.uab.edu/medicine/obgyn/">Department of Obstetrics and Gynecology</a>. “But there are bugs in and on us in many other sites—our skin, our mouths, our noses, our genitalia.”<br />
<br />
During pregnancy, it turns out, the new needs and demands of a woman’s body change the numbers and types of these microbes. Alterations in how the body divvies up nutrients, stores fat, and produces hormones shift the properties of the microbes’ environments. But exactly how the microbiome changes over this nine-month period varies between pregnancies. And these variations, researchers are discovering, could impact not only the well being of a pregnant women herself, but the likelihood of pregnancy complications and the long-term health of a baby.<br />
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<tr><td style="text-align: center;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEiGMHrZ3fuL1aTNuT1t2fBVnZ3cCoiWrqzkSEBdilf7Kb-MYxtmq5C1iwefYoPtrdQgVh1dMTt5cdYbTPeTkoR_Qv1mvDtqvhAwvbnrRnv5RAlMjNHS2bGFQohh4Qi22ywvY2Y6muVVcm-G/s1600/Rodney_Edwards_300.jpg" imageanchor="1" style="clear: right; margin-bottom: 1em; margin-left: auto; margin-right: auto;"><img border="0" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEiGMHrZ3fuL1aTNuT1t2fBVnZ3cCoiWrqzkSEBdilf7Kb-MYxtmq5C1iwefYoPtrdQgVh1dMTt5cdYbTPeTkoR_Qv1mvDtqvhAwvbnrRnv5RAlMjNHS2bGFQohh4Qi22ywvY2Y6muVVcm-G/s1600/Rodney_Edwards_300.jpg" height="320" width="222" /></a></td></tr>
<tr><td class="tr-caption" style="text-align: center;">Rodney Edwards has launched a <br />
research program to probe how the<br />
microbiome of an expectant mother shapes<br />
maternal and fetal health. </td></tr>
</tbody></table>
Edwards has launched a research program in the <a href="http://www.uab.edu/medicine/home/">UAB School of Medicine</a> to probe how the microbiome of an expectant mother—especially the flora that inhabit the genital tract—shape maternal and fetal health. He wants to know if the microbiome’s composition could make a woman go into labor early, or influence a baby’s chance of developing asthma or allergies, among other questions. <br />
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“If we could find a few organisms that—when present in the microbiome—were associated with a particular pregnancy or childhood outcome,” Edwards says, “we could use it as a targeted test for high-risk pregnancies and test putative interventions in that group.”<br />
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<h3>
Investing in the Microbiome</h3>
<br />
Over the past decade, scientists around the world—armed with the new ability to take a genetic snapshot of the microbiome in any person at any given time—have been probing how changes to the microbe populations in a person’s gut can make them sick, weaken their immune system, or even change their risk of cancer or heart disease. <br />
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A few years ago, when the National Institute of Health’s Human Microbiome Project was announcing its early results, Casey Morrow, Ph.D., a professor in the <a href="http://www.uab.edu/medicine/cdib/">UAB Department of Cell, Developmental and Integrative Biology</a>, became excited about the possibilities of microbiome research and the potential to improve human health. <br />
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Morrow’s microbiology laboratory teamed up with UAB’s <a href="http://www.uab.edu/hcgs/genomics-core-lab">Heflin Center for Genomic Science</a>—with its next-generation DNA sequencing capabilities—and bioinformaticians in the <a href="http://www.uab.edu/ccts/Pages/default.aspx">UAB Center for Clinical Translational Science</a> to establish the necessary components at UAB to do microbiome analysis. With early seed support from the UAB Cancer Center and later from the UAB Center for AIDS Research and School of Medicine, they were able to launch a shared facility supporting microbiome research. <br />
<br />
Today, barely two years later, the UAB Microbiome Resource is flourishing, says Morrow. “Any UAB researcher who wants to analyze a microbiome can submit a sample to the facility and from the microbiome analysis pipeline established at UAB can determine what microbes are present,” he says. <br />
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<tr><td style="text-align: center;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgzFAj1YH8mdkuNE-j9QzIF4p0D5ONdy1BOkzRz623EfZh67ab0UZHNlX-bwxft3_geCW8OuZ0ulBmQ5lwSKv87ACDXtlkBSDRBNxFlzMo5DdMvfq0E_c6bcC0yW1P7MHpcEY1uWi6W56Dc/s1600/mix_Casey_Morrow_2014-1.jpg" imageanchor="1" style="clear: left; margin-bottom: 1em; margin-left: auto; margin-right: auto;"><img border="0" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgzFAj1YH8mdkuNE-j9QzIF4p0D5ONdy1BOkzRz623EfZh67ab0UZHNlX-bwxft3_geCW8OuZ0ulBmQ5lwSKv87ACDXtlkBSDRBNxFlzMo5DdMvfq0E_c6bcC0yW1P7MHpcEY1uWi6W56Dc/s1600/mix_Casey_Morrow_2014-1.jpg" height="320" width="222" /></a></td></tr>
<tr><td class="tr-caption" style="text-align: center;">Casey Morrow says the UAB Microbiome <br />
Resource gives researchers a strong<br />
foundation to link basic science <br />
and clinical science.</td></tr>
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“Armed with that analysis, researchers can start figuring out the differences between different samples and what those differences might say about disease states,” says Morrow. “This is really giving us a strong foundation to link basic science and clinical science when it comes to the microbiome.”<br />
<br />
UAB researchers are already studying how the gut microbiome could influence colon, breast, stomach, pancreatic, and brain cancer; how chronic infections in the digestive system can be cured by restoring microbial populations; and how chemotherapy and diet change the microbiome.<i> (Learn more about research on <a href="http://www3.ccc.uab.edu/crossroads/july-2014/#/4">cancer and the microbiome</a> in the latest issue of the UAB Comprehensive Cancer Center magazine.)</i><br />
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<h3>
Beginning with Bacterial Infections</h3>
<br />
Edwards’ interest in the microbiome began not with basic science, but with a clinical question: Why does bacterial vaginosis (BV) during pregnancy increase the risk of preterm births and low birth weight babies? BV is not an infection but rather a condition in which the normal flora of the vagina, dominated by <i>Lactobacilli</i>, is replaced by a mix of bacteria dominated by anaerobes and Gram-negative aerobic bacteria. BV increases the risk of going into labor before 39 weeks of gestation. But when clinicians aggressively screen for and treat BV in populations of pregnant women, they don’t see changes in preterm birth rates. <br />
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Researchers began to understand that BV is what is known as a heterogeneous problem, says Edwards. In other words, “BV in one woman isn’t the same as BV in another.”<br />
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<tr><td class="tr-caption" style="text-align: center;">The UAB Microbiome Resource offers researchers<br />
many ways to analyze samples, including "heatmaps" <br />
depicting levels of various microbes.</td></tr>
</tbody></table>
But classic methods of diagnosing BV didn’t give detailed information about what microbes take over the vagina during an infection—it’s typically diagnosed by measuring the acidity of the vagina (a high pH suggests BV) and looking at a smear from the vagina under a microscope to confirm the presence of bacteria. Edwards, though, wants to get a better sense of the exact species of bacteria normally present in the vagina, how that balance could change in different ways in women with BV, and which variants of BV are most dangerous to pregnant women. <br />
<br />
In a pilot study, UAB researchers collected samples from 19 pregnant women diagnosed with BV. In collaboration with the UAB Microbiome Resource, they were able to detect the identity of the microbes present in each sample. <br />
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“What we’ve already found is that the organisms we used to think were predominant in BV may not actually be predominant,” Edwards says. “At least not in all cases.”<br />
<br />
Now, with the knowledge that microbiome analysis can give more detailed information on a case of BV than classic, microscopy-based approaches, Edwards is moving toward understanding the link with preterm births. To that end, he’s working to establish, within the existing Center for Women’s Reproductive Health, a new UAB Prematurity Prevention and Research Related to the Microbiome (PREPARE-M) Clinic.<br />
<br />
His first project within the new clinic: prospectively following women throughout pregnancy to track changes to their microbiomes. The women he plans to initially follow are those who have previously had a preterm birth, putting them at high risk of repeating that outcome. He’s <a href="http://www.uab.edu/medicine/news/latest/item/277-uab-awards-1-5-million-in-research-grants-to-faculty">received a grant</a> from the General Endowment Fund of the UA Health Sciences Foundation to get the study off the ground. <br />
<br />
If he can find specific subsets of BV that increase a woman’s chance of preterm birth, Edwards believes clinicians will be well on their way to determine how to best treat these women to decrease those odds. <br />
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<h3>
Microbes Linger Long-Term </h3>
<br />
Simply preventing preterm births—at least those associated with infections—is a leap toward improving infant health, as babies born preterm are prone to health problems. But Edwards thinks that a mother’s microbiome does far more than affect her chances of an early delivery. <br />
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<tr> <td><span style="font-size: 14pt;"><b>"There could be something we should be doing immediately after childbirth to make sure a baby's microbiome is shaped properly," Edwards says. "And this could have long-term childhood effects."</b></span></td> </tr>
</tbody> </table>
In the PREPARE-M Clinic, Edwards has launched a long-term study on how the transfer of microbes from mother to baby—which some researchers have found happens even in the womb—could alter a child’s health for years down the road. Initially, he’s going to follow mothers and children only through their first post-partum doctor’s visit, six weeks after birth. But eventually, he’d like to follow children through their fifth birthday. <br />
<br />
“There could be something we should be doing immediately after childbirth to make sure a baby’s microbiome is shaped properly,” Edwards says. “And this could have long-term childhood effects.”<br />
Of course, there are also plentiful basic questions about the genital microbiome: how it’s shaped by the microbes of the gut or skin, how it interacts with the immune system, and how it changes over a person’s lifetime. “Scientists have been studying the gut microbiome for 15 years now,” Edwards says, “But the applications to the vagina and obstetrics are even newer. So we have more basic questions left to answer.”<br />
<br />
One day, microbiome analysis could become commonplace—not only during pregnancy, but at doctor’s visits throughout a person’s life, Morrow says. “Just as your doctor takes a blood sample today, taking samples of your microbiome to make sure your microbes are all in balance will become routine. We anticipate that 'microbiome management' will be an important component of a personalized medicine plan to monitor and improve human health.”<br />
<br />
<i>—Written by Sarah C.P. Williams</i>Unknownnoreply@blogger.com0tag:blogger.com,1999:blog-4162601566541462615.post-59108841263599560192014-07-16T10:57:00.003-07:002014-07-30T09:22:00.256-07:00Tools of the Trade: Scanning Electron Microscope<div class="separator" style="clear: both; text-align: center;">
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<tr><td class="tr-caption" style="text-align: center;">The high-tech look of UAB's Scanning Electron Microscope facility makes it a popular spot on campus tours, but the machine's ability to image everything from exotic metals to living tissues makes it an invaluable research tool, says facility director William Stonewall Monroe (above).</td></tr>
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When you need to see something so tiny that light skips right over it—and you don't want it vacuum-sealed and messed with in the way that a transmission electron microscope requires—you're in the market for a scanning electron microscope (SEM).<br />
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An SEM is the go-to machine for materials engineers, who are very interested in close-up pictures of faulty pipes or the inner workings of exotic, lab-created composites. That's why UAB's SEM is located on the ground floor of the <a href="http://www.uab.edu/engineering/home/">School of Engineering</a>. But the device is also gaining a following with researchers all over campus, says William Stonewall Monroe, director of the <a href="https://labs.uab.edu/wsmonroe/">UAB Scanning Electron Microscope</a> facility.<br />
<br />
"If you want to look inside something, you use a transmission electron microscope," Monroe says. "That's what most people think of as an electron microscope. But the samples have to be elaborately prepared and able to survive the vacuum conditions."<br />
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The SEM only shows the surface of an object, but its prep requirements are much more forgiving. And what it lacks in clarity—it can magnify objects up to 30,000 times, as opposed to the millions of times that a transmission electron microscope can achieve—it makes up in versatility. (There are several TEMs in the <a href="http://www.uab.edu/highresolutionimaging/">UAB High Resolution Imaging Facility</a>.)<br />
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In its environmental mode, "we can put things that are still wet into this microscope," says Monroe. Researchers from the Department of Pathology are using the SEM to examine bone slices. A group in the Department of Physics is poring over its nanodiamonds in the device. And biologists are using it to look at how various processes affect cell growth. "They've been surprised by how much they can see," Monroe says.<br />
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjqRNP9p4QOM4i85zvqKAu3qxrFkoP0RVFEff84ubKoTqp9cE3QLU7BA32raFkaN315BK8JY72CdL2z-FygVTV9uuauW_vgkpysxwlNIkl1YvaB2eZSIEYI5TJ066ThTvyX8shzHNaExvcu/s1600/mix_william_monroe-17_600.jpg" imageanchor="1"><img border="0" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjqRNP9p4QOM4i85zvqKAu3qxrFkoP0RVFEff84ubKoTqp9cE3QLU7BA32raFkaN315BK8JY72CdL2z-FygVTV9uuauW_vgkpysxwlNIkl1YvaB2eZSIEYI5TJ066ThTvyX8shzHNaExvcu/s1600/mix_william_monroe-17_600.jpg" /></a></div>
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Monroe spends his days at the Star Trek-style controls of the SEM, adjusting a range of dials and settings to bring out glorious details in a shattered pipe or sliver of sea urchin. Researchers often sit next to him while he works, observing the results on the lab's giant overhead flat-screen monitors. [The lab is so sleek it is a popular spot on campus tours.] The images he acquires help advance research; they also help it attract attention. "A picture really helps your case if you are publishing," Monroe observes.<br />
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Because the SEM lab is open to any investigator on campus, "I get to see research from all over," Monroe says. "It's a fascinating job."<br />
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<h4>
More Information</h4>
The Scanning Electron Microscope facility is open to academic and commercial users, both from UAB and outside the institution. <a href="http://labs.uab.edu/wsmonroe/">Learn more about rates and booking time. </a>Unknownnoreply@blogger.com0tag:blogger.com,1999:blog-4162601566541462615.post-16559596271781456342014-06-25T06:57:00.000-07:002014-07-30T09:28:17.024-07:00A Parkinson's therapy makes its way through the "valley of death"<br />
<table align="center" cellpadding="0" cellspacing="0" class="tr-caption-container" style="margin-left: auto; margin-right: auto; text-align: center;"><tbody>
<tr><td style="text-align: center;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhlAR0CwgyWgVcGd3xsUhL7VG23hvAk7_cEibKD-ip6gHbf4GbGanoKs6h2txA6N9c5JWUxG0nvLvH0O4AeUFGGiog408OwU41wmVBn2irF9vNCZIAJ8VEkFHWsJ5BiwpwQYEcyyaMZgdCA/s1600/andrew_west.jpg" imageanchor="1" style="margin-left: auto; margin-right: auto;"><img border="0" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhlAR0CwgyWgVcGd3xsUhL7VG23hvAk7_cEibKD-ip6gHbf4GbGanoKs6h2txA6N9c5JWUxG0nvLvH0O4AeUFGGiog408OwU41wmVBn2irF9vNCZIAJ8VEkFHWsJ5BiwpwQYEcyyaMZgdCA/s1600/andrew_west.jpg" /></a></td></tr>
<tr><td class="tr-caption" style="text-align: center;">Andrew West is pursuing a compound to inhibit LRRK2, an enzyme that appears to be a central enabler <br />
of the brain cell death seen in Parkinson's disease.</td></tr>
</tbody></table>
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<br />
In its long journey from the petri dish to the first human patient, every new drug has to cross a wasteland called the "valley of death." Therapeutic programs enter, but most don’t come out the other side.<br />
<br />
"The government is good at funding basic research to identify drug targets, and Big Pharma is good at taking drugs and putting them through clinical trials," says Andrew West, Ph.D., John A. and Ruth R. Jurenko Endowed Professor in <a href="http://www.uab.edu/medicine/neurology/">Neurology</a> at UAB. "But all of the in-between work, the pre-clinical and drug development components, is called the 'valley of death' for research, because nobody funds it, nobody pays attention to it. That's a big part of the lack of new drugs."<br />
<br />
In fact, less than 10 percent of drugs that make it into preclinical testing will end up getting FDA approval, according to the agency's figures. But West is part of a new approach to the drug-discovery process designed to upend those odds: a partnership between UAB and Birmingham-based <a href="http://www.southernresearch.org/">Southern Research Institute</a> known as the <a href="http://www.uab.edu/medicine/adda/">Alabama Drug Discovery Alliance</a> (ADDA).<br />
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The partnership is built around the strengths of each institution. UAB labs identify molecular targets that play a key role in disease. In West's case, that's the enzyme LRRK2 (pronounced "lark two"), which appears to be a central enabler of the brain cell death seen in Parkinson's disease.<br />
<br />
Southern Research has decades of experience in drug discovery and testing. It employs a host of researchers who are adept at the chemical tweaking needed to make a drug work in humans. Southern Research scientists are also experts at proving a drug's safety and efficacy to the FDA and to large pharmaceutical companies. Big Pharma is often willing to step in and fund new drug projects—but only after they have demonstrated initial success.<br />
<br />
Thanks to several years of work, "we're most of the way through the valley of death now," West says. "We have dozens of compounds that are fantastic drugs. We just have a little bit left to go—sometimes the last mile of the marathon can be the most painful."<br />
<br />
<h4>
On the Move</h4>
<br />
In June 2014, West's lab <a href="http://www.uab.edu/news/innovation/item/4796-lrrk2-inhibitors-may-be-key-to-combating-parkinson-s-disease-uab-study-says">published a new study</a> in the Proceedings of the National Academy of Sciences that suggests LRRK2 inhibitors could play a wide role in slowing the progression of Parkinson's disease, or even preventing it altogether.<br />
<br />
"This is a critical first step showing that inhibition of LRRK2 may be beneficial to protect against the cell loss and degeneration that occurs in Parkinson's disease," says West. It's another sign that the team's approach is taking it in the right direction across the valley of death—and a welcome oasis to recharge their efforts.<br />
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<tr><td style="text-align: center;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgkuAI6nSkIlc3uudKloVxgIjKI-j9oz6U0FI3vADBUlk8VAA9FjL3vEkTHq9CwW0UKqjpA13boAh30ay6cubaQmFF39qnOhJVw6jzLHthpMsdcyfPiH6lA-0dK_LsUQxFrEFYzaKf9UFQn/s1600/HTS-robot3.jpg" imageanchor="1" style="margin-left: auto; margin-right: auto;"><img border="0" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgkuAI6nSkIlc3uudKloVxgIjKI-j9oz6U0FI3vADBUlk8VAA9FjL3vEkTHq9CwW0UKqjpA13boAh30ay6cubaQmFF39qnOhJVw6jzLHthpMsdcyfPiH6lA-0dK_LsUQxFrEFYzaKf9UFQn/s1600/HTS-robot3.jpg" /></a></td></tr>
<tr><td class="tr-caption" style="text-align: center;">Robotic systems at Southern Research Institute allow UAB investigators such as Andrew West <br />
to screen hundreds of thousands of potential compounds to find the best candidates for new therapeutics.</td></tr>
</tbody></table>
<br />
<h4>
Screen Team</h4>
<br />
The LRRK2 project's first step was high-throughput screening—using the advanced robotic testing machines at Southern Research to analyze hundreds of thousands of potential compounds and find candidates capable of slowing down LRRK2.<br />
<br />
They emerged with hundreds of potential compounds. Further analysis has whittled that down to the best candidates. What makes a "drug great in a tissue culture dish may not be a great thing for a preclinical candidate," West says. "We want to know how well it crosses the blood-brain barrier, if it interacts with any other protein besides LRRK2, how fast it metabolizes, if it collects anywhere abnormally in the body, and if it causes toxicity."<br />
<br />
Medicinal chemists at Southern Research specialize in taking promising chemicals and tweaking them to make them even better. "We make very small changes," says West. "We'll put a nitrogen here, a carbon there, and look at the effects in a hypothesis-driven way."<br />
<br />
The collective knowledge of the Southern Research scientists is an extremely valuable resource, West emphasizes. "Most of the time you only see these people at big pharmaceutical companies. The relationship between UAB and Southern Research in the ADDA is unique. I haven't seen it built anywhere else in the country, where we get a high-throughput group, drug development group, and biologists sitting at the same table every two weeks discussing the issues."<br />
<br />
<h4>
Getting Close</h4>
<br />
In the next few months, West's lab will evaluate each remaining compound in its animal models of Parkinson's disease. The best ones will then move into toxicology studies, "and hopefully next year we'll begin first-in-man studies," West says.<br />
<br />
The team has already come very close. "We had a great candidate last year that passed all of the key measures," West says. "It went to the brain perfectly, had good potency, seemed to only interact with LRRK2, no side effects, no toxicity." But when the drug got to living models, "we discovered that the metabolism was way off the charts," says West. "It only survived 15-20 minutes in the body before it was destroyed by the liver. We were close—if we could just have slowed what the liver did by a little bit, we'd be in humans now. But it turns out that was not the right molecular scaffold."<br />
<br />
The good news, says West, is that "we have two or three other series that are getting to that same point now." Even more important, he says, "we have a clear pipeline to go to a phase 1 clinical trial," the first evaluation of a potential new drug in humans.<br />
<br />
<h4>
Strong Local Support</h4>
<br />
It's important to note that these advances have been accelerated significantly "through local philanthropic support," says West. "There are many people in this area who are disappointed to see that the government doesn't fund a lot of research into Parkinson's disease cures. I think patients are frustrated. You get a diagnosis of Parkinson's disease and there is nothing you can do to stop it. The best advance we have, L-dopa, was developed 50 years ago. There’s really been no breakthrough like that since."<br />
<br />
But West is convinced that is about to change. "As soon as I found during post-doctoral work in 2006 that all mutations we know about that cause Parkinson's disease increase LRRK2 activity, the next step in my career was finding somewhere I could do something about that," he says. "And the only place I found in the country was Birmingham, so I moved here immediately."<br />
<br />
Now, eight years later, the end may be in sight. "We have to take these drugs to the next level and make them suitable for use in humans," West says. "It's a formidable trek, but I think we have some really good compounds, and more important, the right people that will get us there."<br />
<br />
<hr />
<br />
<h4>
Join In</h4>
<a href="https://www.uab.edu/give/now/index.php?option=com_rsform&formId=4&fundid=1071|Alabama%20Drug%20Discovery%20Alliance%20Expansion%20and%20Acceleration%20Initiative">Give something and change everything with the Alabama Drug Discovery Alliance's Expansion and Acceleration Initiative.</a><br />
<br />
<br />
<br />Unknownnoreply@blogger.com1tag:blogger.com,1999:blog-4162601566541462615.post-55823420956983385192014-06-13T10:48:00.000-07:002014-07-30T09:23:46.051-07:00The Mix Quiz: Are You Smarter Than a Medical Resident?Just like you, doctors love their smartphones. And they like playing games. But a new game pioneered at the <a href="http://www.uab.edu/medicine/home/">UAB School of Medicine</a> has lots more ROI than Farmville. <br />
<br />
It's called Kaizen, a word borrowed from the Japanese auto industry that means something like "continuous improvement." This Web-based quiz game challenges medical residents at the School of Medicine's campuses in Birmingham and Huntsville with two questions every day. They're brief scenarios meant to highlight key practice skills and new evidence-based findings from a range of specialties.<br />
<br />
Learn all about Kaizen in <a href="http://www.uab.edu/uabmagazine/kaizen">this feature from UAB Magazine</a>. And test your medical knowledge with our five-question quiz.<br />
<a name='more'></a><br />
<br />
<br />
<div class="quizz-container" data-auto-redirect="true" data-height="auto" data-quiz="9082" data-width="100%">
</div>
<script async="" src="//dcc4iyjchzom0.cloudfront.net/widget/loader.js"></script>Unknownnoreply@blogger.com0tag:blogger.com,1999:blog-4162601566541462615.post-70328800103101448392014-06-06T11:17:00.001-07:002014-07-30T09:24:25.158-07:00Hit man: A suspect emerges in the chaos of aggressive brain cancer<table align="center" cellpadding="0" cellspacing="0" class="tr-caption-container" style="margin-left: auto; margin-right: auto; text-align: center;"><tbody>
<tr><td style="text-align: center;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjPz6WjAc86xe7rGSUxWhIyN-D6CCNlWuJ6JYAScrGShc4VSDX2lQ6BkDyqXxpuq0mXtywpKq6e1q7DXOHihIlKQ_efYXcHfSeSC6Vk-y_nBdTzF5cOy51z4B2ovm-VmA3dbgzlODYCUnbS/s1600/smANXA7-4.jpg" imageanchor="1" style="margin-left: auto; margin-right: auto;"><img border="0" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjPz6WjAc86xe7rGSUxWhIyN-D6CCNlWuJ6JYAScrGShc4VSDX2lQ6BkDyqXxpuq0mXtywpKq6e1q7DXOHihIlKQ_efYXcHfSeSC6Vk-y_nBdTzF5cOy51z4B2ovm-VmA3dbgzlODYCUnbS/s1600/smANXA7-4.jpg" /></a></td></tr>
<tr><td class="tr-caption" style="text-align: center;">New research from UAB oncologist Markus Bredel identifies the splicing enzyme PTBP1 as a key factor <br />
in the spread of glioblastoma multiforme. </td></tr>
</tbody></table>
<div class="MsoNormal">
<br /></div>
<div class="MsoNormal">
Glioblastoma multiforme is one of the deadliest human
cancers. "The tumor can double in size within a few weeks," says
Markus Bredel, M.D., Ph.D., a professor in the <a href="http://www.uab.edu/medicine/radonc/en/">UAB Department of Radiation Oncology</a> and senior scientist in the neuro-oncology program at the <a href="http://www3.ccc.uab.edu/">UAB Comprehensive Cancer Center</a>. "Usually, by the time we see a patient, they often
have apple-size lesions."<o:p></o:p></div>
<div class="MsoNormal">
<br /></div>
<div class="MsoNormal">
That explosive growth "comes with a substantial amount
of genetic chaos," Bredel says. "If you look at the whole genome in a
brain tumor, out of the 30,000 genes, you very often have changes in up to 50
percent; they're up or down, lost, amplified, mutated."<o:p></o:p></div>
<div class="MsoNormal">
<br /></div>
<h4>
A Change for the Worse</h4>
<div class="MsoNormal">
<o:p></o:p></div>
<table cellpadding="0" cellspacing="0" class="tr-caption-container" style="float: right; margin-left: 1em; text-align: right;"><tbody>
<tr><td style="text-align: center;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEiunL9xUsljyQjMBXdXKZpZMVquqxJgUWTTjKV7ljkZ2MgOoCojcunavfW5_jBuqAzpsXhqT70qSBK6_i9C80eK0Su6nLODZHus-u7-74GsbsV_y71Jl1C-uzoqXLI4oE_DOal0N0B3Odk-/s1600/Markus_Bredel_RT.jpg" imageanchor="1" style="clear: right; margin-bottom: 1em; margin-left: auto; margin-right: auto;"><img border="0" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEiunL9xUsljyQjMBXdXKZpZMVquqxJgUWTTjKV7ljkZ2MgOoCojcunavfW5_jBuqAzpsXhqT70qSBK6_i9C80eK0Su6nLODZHus-u7-74GsbsV_y71Jl1C-uzoqXLI4oE_DOal0N0B3Odk-/s1600/Markus_Bredel_RT.jpg" height="320" width="225" /></a></td></tr>
<tr><td class="tr-caption" style="text-align: center;">Markus Bredel</td></tr>
</tbody></table>
<div class="MsoNormal">
But in that chaos, patterns emerge with surprising
regularity, Bredel says. "When Gene A is up, Gene B is very often
down." In two papers published in <i style="mso-bidi-font-style: normal;">JAMA</i>
in 2009, Bredel's research team argued that "there needs to be a reason
why glioblastomas co-select for certain genetic events. The tumor cells must
benefit."<o:p></o:p></div>
<div class="MsoNormal">
<br /></div>
<div class="MsoNormal">
In those papers, Bredel's lab identified dozens of gene-gene
links that were candidates for additional scrutiny. They focused on one
particular pair: The oncogene EGFR, or epidermal growth factor receptor, which
is crucial for normal cell growth and wound healing, and the tumor-suppressor
ANXA7 or annexin A7. EGFR is of interest in many cancers, because it is often
hijacked to fuel the aggressive growth of tumor cells.<o:p></o:p></div>
<div class="MsoNormal">
<br /></div>
<div class="MsoNormal">
"We found that ANXA7 is probably a regulator of
EGFR," Bredel says. "So it's to the benefit of the tumor cell to
knock down this regulator." But it wasn't clear at the time how this was
happening. "ANXA7 resides on a different chromosome from EGFR, so it's a
completely independent event, but somehow the tumor cells were disabling it,"
says Bredel.<br />
<a name='more'></a><o:p></o:p></div>
<div class="MsoNormal">
<br /></div>
<div class="MsoNormal">
Now, in a <a href="http://www.jci.org/articles/view/68836">paper published May 27</a> in the Journal of Clinical
Investigation, Bredel's lab has revealed how ANXA7 normally keeps EGFR in
check—and how cancer cells manage to sabotage this system. Those discoveries
have also identified a promising new target for treating glioblastoma, a cancer
with few therapeutic options.<o:p></o:p></div>
<div class="MsoNormal">
<br /></div>
<h4>
<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgnPI1rtrMJTLCyY_ZrWlj-2KK8od8cju5zIgv8xHbIZslV5_zQ37-bwdrbaExxHpjVQ_3NLHo8CgzYBPxQHcWLmmTOe2jBXzHBuKz0ozjLI63FjL7w34LXIy5b1LpCYgyFij9yufwx0_bN/s1600/ANXA7-1.jpg" imageanchor="1" style="clear: right; float: right; margin-bottom: 1em; margin-left: 1em;"><img border="0" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgnPI1rtrMJTLCyY_ZrWlj-2KK8od8cju5zIgv8xHbIZslV5_zQ37-bwdrbaExxHpjVQ_3NLHo8CgzYBPxQHcWLmmTOe2jBXzHBuKz0ozjLI63FjL7w34LXIy5b1LpCYgyFij9yufwx0_bN/s1600/ANXA7-1.jpg" height="320" style="cursor: move;" width="320" /></a>Taking Out the Trash</h4>
<div class="MsoNormal">
<o:p></o:p></div>
<div class="MsoNormal">
Normal cells have ways of dealing with proteins that get too
big for their britches. Cellular structures called endosomes degrade the
proteins, acting as the "trash cans" of the cell, Bredel explains.
"What we found is that ANXA7 promotes the sorting of EGFR into those trash
cans."<o:p></o:p></div>
<div class="MsoNormal">
<br /></div>
<div class="MsoNormal">
Here's one way to think about the relationship, Bredel says:
"EGFR is kind of the bad guy in the cells. When it's present, it promotes
the tumor process. ANXA7 is the police, which under usual conditions constrains
the bad guy. But in the absence of the police force, the bad guy can do
whatever he wants."<o:p></o:p></div>
<div class="MsoNormal">
<br /></div>
<div class="MsoNormal">
<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjCyZbRnB-tptBmFuKA6JUSarsC9PJadGAJ7YsTSuiXelRmSzTz83r1nun4J_uU2egcIXQQYdhSqaE3zy2nE-HxVh54aEQde1rIIH-CpTplHOwhY-mbHH68h2NxjxFyObJ0TEtL-C3hVEXQ/s1600/ANXA7-2.jpg" imageanchor="1" style="clear: right; float: right; margin-bottom: 1em; margin-left: 1em;"><img border="0" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjCyZbRnB-tptBmFuKA6JUSarsC9PJadGAJ7YsTSuiXelRmSzTz83r1nun4J_uU2egcIXQQYdhSqaE3zy2nE-HxVh54aEQde1rIIH-CpTplHOwhY-mbHH68h2NxjxFyObJ0TEtL-C3hVEXQ/s1600/ANXA7-2.jpg" height="320" width="320" /></a>But what is taking out the police force in glioblastoma?
Bredel's team started with an observation: A "long form" of the ANXA7
gene exists in normal brain cells, but an altered version appears in
glioblastomas.<o:p></o:p></div>
<div class="MsoNormal">
<br /></div>
<div class="MsoNormal">
Genes contain the code that tells the cell's factories how
to make their specialized product—usually a protein. The parts of the gene that
actually contain instructions are known as exons. Each of the exons in a gene
codes for the amino-acid "building blocks" that make up each protein. (In between are non-coding sections: the introns.) In glioblastoma, Bredel found,
exon 6 was missing from the ANXA7 gene. "Without exon 6, ANXA7 can't sort
EGFR to the cell's trash cans," says Bredel. The "bad guy" has
free rein.</div>
<div class="MsoNormal">
<br /></div>
<h4>
Follow the Slices</h4>
<div class="MsoNormal">
<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgCQn8l-ue9NITBQT9Jq-JwV5xenhyphenhyphenPgWp4Hqv8h64sDPBzItTSXiQBmXlJUkqwm1eqb0iWMOS88a9C0yqpSGLriYKhB8LWFxLWCGqGEQypNWNf7R8T28gVvC7iSidt2IhelBGOPXC0cNkh/s1600/ANXA7-3.jpg" imageanchor="1" style="clear: right; float: right; margin-bottom: 1em; margin-left: 1em;"><img border="0" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgCQn8l-ue9NITBQT9Jq-JwV5xenhyphenhyphenPgWp4Hqv8h64sDPBzItTSXiQBmXlJUkqwm1eqb0iWMOS88a9C0yqpSGLriYKhB8LWFxLWCGqGEQypNWNf7R8T28gVvC7iSidt2IhelBGOPXC0cNkh/s1600/ANXA7-3.jpg" height="320" width="320" /></a>Clearly, something is snipping exon 6 out of the picture. But that isn't necessarily abnormal. "In the past 15 years, we've realized
that gene splicing plays a role in many biological processes, both normal ones
and disease processes," Bredel says. Splicing is a way to increase
efficiency; it allows the same gene to produce different proteins, depending on
which of the underlying amino-acid parts are used.<o:p></o:p></div>
<div class="MsoNormal">
<br /></div>
<div class="MsoNormal">
To turn a gene into a specific isoform of a protein, the
cell's copying mechanisms cut out the exons and stitch them together to form an
uninterrupted message. The cutting is the job of splicing factors, and Bredel's
attention focused on one: PTBP1.<o:p></o:p></div>
<div class="MsoNormal">
<br /></div>
<div class="MsoNormal">
<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEiQbeHCSTYFfh-2h6k7yV7SUGZaXsOP9Gj_7tR3bCw7gOI9QvTOl453p1DokIj0vGIJWKjbJvVWgx4XvXN2b5StQU_zzflcjkJVpxlpv9uvRzI-ZtSsFhR-fDXxvRSb9xkHQvIY0dgBJPHl/s1600/ANXA7-4.jpg" imageanchor="1" style="clear: right; float: right; margin-bottom: 1em; margin-left: 1em;"><img border="0" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEiQbeHCSTYFfh-2h6k7yV7SUGZaXsOP9Gj_7tR3bCw7gOI9QvTOl453p1DokIj0vGIJWKjbJvVWgx4XvXN2b5StQU_zzflcjkJVpxlpv9uvRzI-ZtSsFhR-fDXxvRSb9xkHQvIY0dgBJPHl/s1600/ANXA7-4.jpg" height="320" width="320" /></a>Exon 6 is what is known as a "cassette exon," or
"alternative exon," a section of the code that appears in that gene
in some body tissues but not others. "A cassette exon might be present in
the brain but not in the muscle tissue, for instance," Bredel says. In his
team's latest paper, "we figured out that the PTBP1 gene is the splice
factor that cuts cassette exon 6 out of ANXA7," he continues. They also
established that PTBP1 proteins are overproduced in glioblastoma compared to
normal brain tissue.<o:p></o:p></div>
<div class="MsoNormal">
<br /></div>
<div class="MsoNormal">
<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgPrGmRtrOY2r1RO-bO9QM_97oF-rpg6wiIyj73msAtbnsjoWoRFY6k1us5bGmoWPaRwT3evMIHcFYdobAan4dUpci_C2iQ8olfNFuDyyIWyklVLI49AK2cqpjJdTfiFcl-QEajVJ34U3nv/s1600/ANXA7-5.jpg" imageanchor="1" style="clear: right; float: right; margin-bottom: 1em; margin-left: 1em;"><img border="0" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgPrGmRtrOY2r1RO-bO9QM_97oF-rpg6wiIyj73msAtbnsjoWoRFY6k1us5bGmoWPaRwT3evMIHcFYdobAan4dUpci_C2iQ8olfNFuDyyIWyklVLI49AK2cqpjJdTfiFcl-QEajVJ34U3nv/s1600/ANXA7-5.jpg" height="320" width="320" /></a>So PTBP1 turns bad in cancer, guts a key exon from ANXA7,
and allows EGFR to replicate like crazy. Well... not quite, says Bredel. It's
even more interesting than that. "We initially thought that this splicing
was something specific to tumor cells, that it might even be an initiating
event that allows the tumors to emerge," he says. But when the researchers
looked at a set of normal brain cells called precursor cells or stem cells,
they found this same ANXA7 splicing going on. "It wasn't present in mature
neurons, but in the immature cells, the stem cells, there it was," says
Bredel.<o:p></o:p></div>
<div class="MsoNormal">
<br /></div>
<h4>
Deadly Inheritance</h4>
<div class="MsoNormal">
When you think about it, that makes sense. Neural and glial stem
cells power initial brain development and, as is becoming increasingly clear,
allow us to learn new things over the course of our lives. They also respond to
injury and disease, such as strokes and Parkinson's disease. Having a way to
turn off a growth suppressor like ANXA7 is "a useful trait in the stem
cell, because the stem cells wants to be able to divide and grow," Bredel
says.<o:p></o:p></div>
<div class="MsoNormal">
<br /></div>
<div class="MsoNormal">
The UAB scientists now believe that the ANXA7 splicing in
glioblastoma "is something the tumor cells inherited from the stem cells,
a potential tumor-initiating ancestor of glioblastoma," Bredel says.
"When that stem cell, through accumulation of mutations, develops into a
tumor cell, that splicing trait is still there. And then it's exploited further
by the accumulation of mutations that enhance EGFR signaling." At this
point, Bredel says, "I'm not sure if we can claim this process is involved
in the initiation of glioblastoma, but it certainly is involved in the
progression of glioblastoma."<o:p></o:p></div>
<div class="MsoNormal">
<br /></div>
<div class="MsoNormal">
PTPB1's role in healthy brain stem cells means eliminating
it completely isn't an option. But targeting PTBP1 with the aim of lowering
production to normal levels offers exciting treatment possibilities. Bredel's
lab is now identifying promising compounds that could act on PTBP1. Restoring
tumor suppressors such as ANXA7 directly in cancer hasn't been successful so
far, Bredel says. "Having something that is operating in excess that we
can target, like PTBP1, is much easier," he notes.<o:p></o:p></div>
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"We haven't been able to make any major, clinically
meaningful progress in glioblastoma in the past 20 years," Bredel adds.
"We are still a long way off from being able to take this to a clinical
trial in patients, but this is an exciting discovery."<o:p></o:p></div>
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</h3>
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<tr><td style="text-align: center;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjdmxt4Ohw05KcVm020igFr_43zcu_49EuCHtzwfKv1KzdnLBxYki406tn0Y3IXDQZ3trlTuDOClPCOEWFjP9b9-8SuJWFM1M_oGF9SKrefjPXpIxT7kgDeJ1mspz5zDYDj_uYbkUSiHZog/s1600/laser_lab-13.jpg" imageanchor="1" style="margin-left: auto; margin-right: auto;"><img border="0" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjdmxt4Ohw05KcVm020igFr_43zcu_49EuCHtzwfKv1KzdnLBxYki406tn0Y3IXDQZ3trlTuDOClPCOEWFjP9b9-8SuJWFM1M_oGF9SKrefjPXpIxT7kgDeJ1mspz5zDYDj_uYbkUSiHZog/s1600/laser_lab-13.jpg" /></a></td></tr>
<tr><td class="tr-caption" style="text-align: center;"><h3>
UAB researchers and colleagues have created an ultrafast, ultratiny
on-off switch out of vanadium dioxide, a material that could be the
future of high-tech. But before we get there, we'll probably need to
answer this question: What in the world is vanadium dioxide, anyway? </h3>
</td></tr>
</tbody></table>
<br />
<h3>
What's the fastest thing you can imagine? How about the smallest? </h3>
Well never mind, because there really is no way to wrap your head around what's going on in David Hilton's <a href="http://people.cas.uab.edu/~dhilton/Quantum_Materials_Lab/Intro.html">laser lab</a> in the <a href="http://www.uab.edu/cas/physics/">UAB Department of Physics</a>. <br />
<br />
That is to say, you're about to find out what's going on, and it's amazing stuff. Hilton and one of his graduate students, Nate Brady, are hot on the trail of what might be the magic material of the 21st century: vanadium dioxide. This strange, manmade material could be the successor to silicon, paving the way to ultrafast, ultrasmall switches that will make the current information superhighway look like a slow drive down a country road.<br />
<br />
But all this is happening so quickly that it staggers the brain.<br />
<a name='more'></a> <br />
<br />
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<tr><td class="tr-caption" style="text-align: center;">Nate Brady (left) and David Hilton (right) worked with researchers from Vanderbilt University and Los Alamos National Laboratory to create an ultrafast switch from vanadium dioxide, a manmade material with unusual properties.</td></tr>
</tbody></table>
<h2>
</h2>
<h3>
Super Cycle </h3>
Vanadium dioxide, also known as VO<span style="font-size: xx-small;">2</span>, has a curious characteristic: below 153 degrees Fahrenheit, it's an insulator; when it hits 153 degrees or higher, VO<span style="font-size: xx-small;">2</span> turns into a metal. "It changes from being transparent to being opaque," says Brady. "It's really cool, especially because it happens so near room temperature that it could be useful in a lot of devices." <br />
<br />
Like, say, ultrafast optical switches, which use photons to transmit a signal instead of electrons. Major computer makers such as Intel and IBM see optical switches as the way out of the current stagnation in computer speeds. (To make a computer processor run faster, you have to add more power. And at a certain point, basically where we are now, going faster means adding so much power that you fry your chip—or the user's legs.) <br />
<br />
"You haven't been able to buy a processor faster than 4 gigahertz, mostly because it's going to melt in your lap," Hilton says. We may have reached the limits of silicon. And that's where VO<span style="font-size: xx-small;">2</span> comes in. <br />
<br />
<h3>
Speed Run </h3>
In the <a href="http://pubs.acs.org/doi/abs/10.1021/nl4044828">March 12, 2014, issue of Nano Letters</a>, Brady and Hilton, along with collaborators at Vanderbilt University and Los Alamos National Laboratory, presented work showing they had reached terahertz speeds, or trillions of cycles per second, in a VO<span style="font-size: xx-small;">2</span>-based switch. Just as important, they did it using as little as one-tenth of the energy required for previous VO<span style="font-size: xx-small;">2</span> switches.<br />
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEg44MkZcAbv2QhPlALdnmNFhAeygEcjl_2HU4iCCpGihWIhAXKBFKDgB_HyBAlcrV7dxpomjdTS3U5KRdJnANi5m1FQ6J2CigrACAFh83zfEV6rYrBKeGpnikeEiV6jzdftW2Zj0CTzpbQe/s1600/VO2-3.jpg" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEg44MkZcAbv2QhPlALdnmNFhAeygEcjl_2HU4iCCpGihWIhAXKBFKDgB_HyBAlcrV7dxpomjdTS3U5KRdJnANi5m1FQ6J2CigrACAFh83zfEV6rYrBKeGpnikeEiV6jzdftW2Zj0CTzpbQe/s1600/VO2-3.jpg" /></a></div>
<br />
<br />
Hilton is quick to point out that this breakthrough is still a long way from your local Best Buy. "We've shown that we can flip one switch on that fast," Hilton says. "To build a processor, we'd need to show we can do a couple billion of them." Long before that point, experimental physicists like Hilton and Brady will have given way to scientists at Intel and other major manufacturers. But right now, Hilton and company are still trying to answer their burning question: What causes vanadium dioxide to change from insulator to metal, anyway? <br />
<br />
"Lots of really smart people have tried to figure that out,” says Hilton. “This is either one of the great questions in condensed matter physics—or Don Quixote's windmill.” <br />
<br />
<h3>
A Brief History of Time </h3>
We humans have a pretty firm grasp of how long a second is. (The word "Mississippi" is often involved.) But a second is built from milliseconds, or thousandths of a second. Remember when <a href="http://sportsillustrated.cnn.com/multimedia/photo_gallery/0808/oly.phelps.sequence/content.1.html">U.S. swimmer Michael Phelps beat Serbia's Milorad Cavic at the Beijing Olympics</a> by a fraction of a fingertip? Phelps' margin of victory was 0.01 seconds, or 10 milliseconds, a distinction so fine it took super-slo-mo video to convince the Serbian delegation it had even happened. <br />
<br />
The next step down from the millisecond is the microsecond, or one millionth of a second. At this point, the human brain is completely out of its depth. A microsecond is to a second as a second is to 11.5 days. <br />
<br />
Next we come to the nanosecond, which is one billionth of a second—the time it takes a 1 gigahertz computer processor to execute one cycle, or the time it takes light to travel 30 centimeters. And underneath the nanosecond is the picosecond, one trillionth of a second. In this range, you're talking about "ultrafast" research. This is David Hilton's neighborhood. <br />
<br />
Picoseconds are a crucial part of vanadium dioxide research. So are femtojoules, the unit of measurement for how much energy it takes to make VO<span style="font-size: xx-small;">2</span> toggle between its transparent and metallic states. It's clear that VO<span style="font-size: xx-small;">2</span> would make a good switch—it lets light through when it's transparent, and blocks light when it's metallic. The problem has been that it takes a relatively large amount of energy to drive that change. <br />
<br />
"With this work, we have lowered the threshold energy needed to undergo the phase transition"—anywhere from one-fifth to one-tenth the energy needed in the past, Brady says. The team’s VO<span style="font-size: xx-small;">2</span> switch generates ten trillionths of a calorie, or 100 femtojoules, per bit. That low energy cost “is going to make the fabrication of these kinds of devices easier," Brady says. <br />
<br />
<h3>
Pass the Picoseconds </h3>
Richard Haglund and his team at Vanderbilt are experts in manipulating VO<span style="font-size: xx-small;">2</span>. For the experiments described in the Nano Letters paper, they created a version with gold nanoparticles studded along the outside like Christmas lights. The idea "is that the nanoparticles act as antennas, focusing the light onto the VO<span style="font-size: xx-small;">2</span>," Hilton says. But if you can't measure the exact point at which the phase transition happens, you can't tell exactly how much energy it takes to trigger that transition. That's where Brady and Hilton came in. <br />
<br />
In 3.3 picoseconds, light travels 1 millimeter. A picosecond is to one second as one second is to 31,700 years. In other words, it passes pretty quickly. "There's not a detector in the world fast enough to measure this," Hilton explains. "That's our specialty here is to be able to do these very fast measurements," often using what are called "pump-probe experiments." This is the realm of the ultrafast, "where 'ultrafast' is a specific word that talks about picosecond or sub-picosecond dynamics," Hilton says.<br />
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhNoqOTbjVkx7i7K_NSsafm1g4IlTo_yEnnVTmED5HKU_R39lIkhfYu5CBWInCf3oYpSwRsT0iS0FS2S8mtgLpQ4Q0SvdfnTDkhtvGVomGTCh3E5NftksNOc1eUiRYZXka-q0VDai1NIShz/s1600/laser_lab-11.jpg" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhNoqOTbjVkx7i7K_NSsafm1g4IlTo_yEnnVTmED5HKU_R39lIkhfYu5CBWInCf3oYpSwRsT0iS0FS2S8mtgLpQ4Q0SvdfnTDkhtvGVomGTCh3E5NftksNOc1eUiRYZXka-q0VDai1NIShz/s1600/laser_lab-11.jpg" /></a></div>
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<br />
In a pump-probe experiment, the pump is an ultrafast laser beam, and the probe is a second beam that arrives at the target slightly later. In this case, the pump excites the VO<span style="font-size: xx-small;">2</span> sample, and then the probe arrives to take note of what happened. Each run offers a data point; by adding up hundreds of data points, you can begin to get a picture of what is going on. <br />
<br />
"This is very much like stop-motion photography," Hilton says. "And the ironic thing about ultrafast research is it takes a very long time to put it together." <br />
<br />
<h3>
Green Screens </h3>
Ultrafast switches aren't the only potential use for VO<span style="font-size: xx-small;">2</span>. Another application, says Hilton, is in "green energy." "You could spray-coat the windows in an office building" with a vanadium dioxide solution, Hilton says. On a really hot summer day, the heat would activate the phase transition and "the windows would darken automatically," which could pay off in lower energy bills. And unlike an existing solution, silver halide, you could simply coat current windows rather than replacing all the glass in an entire building. <br />
<br />
At VO<span style="font-size: xx-small;">2</span>'s current transition point, 153 degrees Fahrenheit, this is still theoretical. "That's pretty hot, even for Alabama in the summer," Hilton jokes. "But if we could get it down to 105 degrees, that's very reasonable." <br />
<br />
<h3>
Weird Science </h3>
Ever since the early 1960s, when VO<span style="font-size: xx-small;">2</span> was first created, it has clearly had plenty of potential. But there is plenty of mystery as well. "It has some aspects of the physics of something like silicon, which is a very well-understood material, and some aspects of a superconductor, which are not nearly as well understood," Hilton says. <br />
<br />
There are many vanadium oxides, but only this one exhibits the insulator-to-metal phase transition. And of all the other materials that undergo that phase transition, VO<span style="font-size: xx-small;">2</span> is one of the few that does so at near room temperature. (Most phase transitions happen at the kind of supercold temperatures that make them of little use for mainstream electronics.) <br />
<br />
Gold nanoparticles are one way to crank down the energy required to drive VO<span style="font-size: xx-small;">2</span>'s phase transition. But Hilton and Brady have lots of other ideas. "We're actually starting to be able to figure out how to play with dials on this phase transition, making it do what we want," Hilton says. <br />
<br />
"The big question for me is our ability to manipulate matter and actually control these transitions, versus simply digging a material out of the ground and just using what nature gives us." <br />
<br />
<h3>
Next-Gen </h3>
Even if the VO<span style="font-size: xx-small;">2</span> switch is years away from powering your laptop, one phase of this research is already in production: Nate Brady himself. He hopes to defend his dissertation this summer and then carry on his research in a position at a national lab like Los Alamos, where Hilton also got his start. <br />
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"The Department of Energy, the National Science Foundation, Department of Defense, and Department of Education are all investing heavily in nanotechnology," Hilton says. Brady is funded by a Department of Education grant, "because we know we need more nanotechnology researchers," Hilton adds. Several other UAB graduate students are funded by similar grants. <br />
<br />
"These agencies know we're going to live and die based on the next generation of scientists that we are training right now to have the next generation of ideas and to push this type of technology forward," Hilton says. "Attracting bright people like Nate into this field is good for UAB—and for our future as a country." Unknownnoreply@blogger.com0tag:blogger.com,1999:blog-4162601566541462615.post-82726218038771583252014-05-02T11:49:00.003-07:002014-07-30T09:25:10.059-07:00Video selfies offer a new way to teach chemistry<table align="center" cellpadding="0" cellspacing="0" class="tr-caption-container" style="margin-left: auto; margin-right: auto; text-align: center;"><tbody>
<tr><td style="text-align: center;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEiC4K9vf3jl4bmXlv0lk2LrgVLLH-RV7qapJQf4fOfgcyY23RHBbvDZfLhCSwnFg-VVtHF0_jgL6hEyE1VNC_Vqz0yD7V_Nko-oN1rRkgt1KQiOhi068SELKvI_b-nt_M4RbY3lj0NVnMup/s1600/_Joe_March__Mitzy_Erdmann.jpg" imageanchor="1" style="margin-left: auto; margin-right: auto;"><img border="0" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEiC4K9vf3jl4bmXlv0lk2LrgVLLH-RV7qapJQf4fOfgcyY23RHBbvDZfLhCSwnFg-VVtHF0_jgL6hEyE1VNC_Vqz0yD7V_Nko-oN1rRkgt1KQiOhi068SELKvI_b-nt_M4RbY3lj0NVnMup/s1600/_Joe_March__Mitzy_Erdmann.jpg" /></a></td></tr>
<tr><td class="tr-caption" style="text-align: center;">Can making movies make you a better chemist? UAB chemistry professor Joe March (left) and graduate student Mitzy Erdmann (right) have proven that it does. Their research-tested approach is now implemented across UAB's introductory General Chemistry curriculum.</td></tr>
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<br />
<br />
<h3>
Hollywood has nothing on the UAB Department of Chemistry. While Tinseltown studios generate some 600 movies per year, students in the university's General Chemistry course produce nearly that many each semester.</h3>
<br />
"Avatar" this is not. Each video clocks in at five minutes or less and follows a strict formula:<br />
<br />
<div style="text-align: center;">
<i>SCENE 1, DAY</i></div>
<div style="text-align: center;">
<i>OPEN in a UAB chemistry lab. THREE or FOUR students take turns demonstrating a fundamental lab technique. Each speaks directly to the camera while they explain how to use a balance, how to pipette, or how to do an accurate titration.</i></div>
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There is no scene 2.<br />
<br />
The teaching assistants who grade dozens of these videos each year may relish the occasional creative approaches, such as the group who adopted a "Star Wars" theme (see below), or the ones who broke for commercials. But entertainment isn't the idea. Call it sci (non)fi.<br />
<a name='more'></a><br />
<br />
<i>(see an example below)</i><br />
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<iframe allowfullscreen="" frameborder="0" height="315" src="//www.youtube.com/embed/I4BMJXge3Ic?rel=0" width="560"></iframe><br />
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<h3>
Formula Flicks</h3>
These videos may never go viral, but they could inspire a new generation of students to pursue virology—or other crucial science careers. The videos have proven themselves to be a remarkably effective—and cheap—teaching tool. And considering that Gen Chem is a foundational course for a host of careers, from medicine to engineering, anything that can improve student learning—and make students more comfortable with crucial lab techniques—is a big deal.<br />
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The Coen Brothers of this movie empire are associate professor Joe March, Ph.D., and graduate student Mitzy Erdmann. They have spent the past four years proving that making movies makes for better chemists. "The impact of seeing yourself do something is greater than seeing someone else do it," March says. In a randomized, controlled trial, he and Erdmann showed that movie-making students "were twice as likely to perform a technique accurately after having shot a video" compared to a control group that received traditional, verbal instruction alone, March says.<br />
<br />
"We are seeing that students are better prepared to go into research labs," March says. That's good news for a major research university like UAB. But it's also good news for the United States, which is desperate to boost enrollment in the STEM (science, technology, engineering, and math) fields in order to maintain its global competitiveness in an increasingly science-centered world.<br />
<br />
Ninety-five percent of Gen Chem students are STEM or pre-health majors, Erdmann says. But few have prior lab experience. As the researchers explain in a paper now under review at the Journal of Chemical Education, "the most technically astute member of the group often becomes responsible for the majority of the data collection" in the average chemistry course, while his or her partners become little more than spectators.<br />
<br />
<h3>
Movie Studio in a Pocket</h3>
March has been pondering this problem for some time. In fact, he is something of a pioneer in chemistry tech. At the University of Wisconsin, March was part of a project called ChemPages, which included expert video demonstrations of basic chemistry lab techniques. ChemPages has been adopted at many universities. "The idea was to show students the technique before they arrived in the lab so they had an idea of what to do," he says. "But I realized it would be a lot more powerful if you could watch yourself in the video."<br />
<br />
March pursued the idea when he came to UAB. In 2010, he and Erdmann answered their first basic research question: Was it reasonable to expect hundreds of freshmen to provide their own cameras? (Buying enough cameras for the 1,500-plus students who take Gen Chem at UAB each year was clearly out of the question.)<br />
<br />
A survey of UAB students showed that the timing was right. "Ten years ago they would have had to buy all the equipment to do something like this," March says. "Today, every study group has at least one person with a phone capable of shooting video."<br />
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<iframe allowfullscreen="" frameborder="0" height="315" src="//www.youtube.com/embed/-wTjOIqxVLs?rel=0" width="560"></iframe><br />
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<h3>
Experimental Filmmaking</h3>
With the access question answered, March and Erdmann piloted an experiment in the Summer 2011 semester. Students got a detailed rubric—in effect a shooting script that told them exactly what they needed to do for the cameras. And teaching assistants provided quick feedback, giving groups a chance to reshoot to improve their grades.<br />
<br />
Some similar projects have been tried in upper-level courses around the country, but never "on a large scale in a freshman chemistry course," Erdmann says. The required techniques are carefully chosen, she adds: "We've picked ones they're going to use again and again."<br />
<br />
In March and Erdmann's research study, an independent proctor evaluated the entire cohort of students as they performed the techniques in the lab. "They didn't know which students had made the videos and which had not," March says. The students who had made videos—and watched themselves in action—were clearly superior.<br />
<br />
Encouraged by the project's success, March and Erdmann rolled it out to ever larger groups in subsequent terms. "Once we decided it was working, we expanded it to all students," March says.<br />
<br />
<h3>
Creative Chemistry</h3>
Junior chemistry major Aaron Alford was part of one of those early experimental cohorts; today he's a teaching assistant in the Gen Chem lab. "Reading through the rubric and then watching yourself do the techniques" is very effective, Alford says. "Now every time I use a balance it's like second nature—it's cemented in."<br />
<br />
The teaching assistants walk through the lab during filming days, coaching students through the techniques and correcting any errors in form. Students are told about the video requirement at the beginning of the semester. "So far, I've only ever had one group that didn't have a smartphone or video camera of some kind between them," Erdmann says. "And we dealt with that quickly by just swapping members between groups."<br />
<br />
Presentation only accounts for two out of the 25 maximum points for the videos, but many groups go above and beyond to add some artistry to their films. "A good three-quarters of my students do pretty substantial editing," Erdmann says.<br />
<br />
During his time in the class, "we decided to get the footage and then dub over it with a scripted voiceover," Alford says. Then he got a roommate who was majoring in film to edit the project with professional-level Final Cut software. He did the job himself for his second and third videos, using Apple's consumer-grade iMovie application.<br />
<br />
But students don't need to have their own video editing software. The <a href="http://www.uab.edu/cas/digitalmedia/">Digital Media Commons</a> lab in the <a href="http://www.uab.edu/cas/home/">College of Arts and Sciences</a> is open to all students. The lab is equipped with a host of workstations and the latest video editing tools. "When we opened the lab, some of the first people who came in were chemistry students," says Rosie O'Beirne, director of Digital Media and Learning at UAB. "We're seeing a lot of foot traffic from science students."<br />
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<br />
<h3>
Social Success</h3>
Enrollment in Gen Chem is soaring. "UAB is heavily recruiting science majors" to help fuel the nation's drive for STEM students, March points out. "Our enrollment has doubled in the past few years," and currently stands at more than 1,500—95 percent of whom are STEM or pre-health majors.<br />
That makes for a lot of videos for TAs like Alford and Erdmann to watch. "When they get creative it's always fun," Alford says. "One group took a Star Wars template and put important text in that, then cut to the regular video of them doing the technique. Some use music. One group paused for commercials."<br />
Student engagement is a key ingredient in good teaching. And it gives visual and auditory learners a chance to shine, Erdmann says. Now, "we're trying to see if we can expand it—such as having students do actual lab reports on video," she says.<br />
<br />
The lessons could be easily adapted beyond the lab, March adds. "It's an interesting alternate assessment technique for the sciences, but I think it has implications in the humanities as well," he says. "Whenever students can see themselves in a video, it has the opportunity for more impact. And they're more likely to share the lesson with family and friends through social media. We've shown that modern technology has a good educational foundation. This opens up lots of different possibilities."<br />
<div>
<br />
<h3>
Learn More</h3>
<a href="http://www.uab.edu/cas/chemistry/">UAB Department of Chemistry</a></div>
Unknownnoreply@blogger.com0tag:blogger.com,1999:blog-4162601566541462615.post-44103162183275648132014-04-28T05:51:00.001-07:002014-04-28T05:51:18.353-07:00There and back again: Space protein research at ISS, in Smithsonian<table align="center" cellpadding="0" cellspacing="0" class="tr-caption-container" style="margin-left: auto; margin-right: auto; text-align: center;"><tbody>
<tr><td style="text-align: center;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjcwDDtXlwxsIVbVlsfxAMmrgfWhqOlbVRNdCbP8Q9JC7X-NCX-CuWVWWZ7FRkC2xR0XTFWTv901DzhehXis-_0FtiCGy7PG0LkLgjTh7tRVezVkGg74iW8ssh0r2omQAI2AvivKGuzrzHw/s1600/mix_dragon_capture.jpg" imageanchor="1" style="margin-left: auto; margin-right: auto;"><img border="0" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjcwDDtXlwxsIVbVlsfxAMmrgfWhqOlbVRNdCbP8Q9JC7X-NCX-CuWVWWZ7FRkC2xR0XTFWTv901DzhehXis-_0FtiCGy7PG0LkLgjTh7tRVezVkGg74iW8ssh0r2omQAI2AvivKGuzrzHw/s1600/mix_dragon_capture.jpg" /></a></td></tr>
<tr><td class="tr-caption" style="text-align: center;">The SpaceX Dragon 3 capsule, carrying crucial protein crystal experiments from UAB, docked to the International Space Station on April 25. Image courtesy SpaceX.</td></tr>
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<br />
On April 18, UAB's <a href="http://themixuab.blogspot.com/2014/03/watch-uab-research-ride-into-space-on.html">protein crystal experiments</a> leapt into orbit aboard the SpaceX Dragon rocket. Check out some very cool photos and follow the mission live at <a href="http://www.spacex.com/webcast/">www.spacex.com/webcast/</a>. The experiments will take place aboard the International Space Station; want to find out when it passes overhead? Just visit the <a href="http://www.isstracker.com/">live tracker here</a>.<br />
<br />
While that work is going on in orbit, you can learn more about the history-making aspects of UAB's protein crystal expertise on the ground — in an exhibit now on display in Washington, D.C.<br />
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgCz4vqaA8vRKTazlupqaS49fDVJLJqywXYt0vjXUvAdiwgDgPyFiyTBjkxdKmkPSK8VjNa1jwGHA0PKzbVxkqIiidIPpiVhPiJWmLam0psMn3NosB1ZM8So2lShNhxqq8QCJLrN5oMsOn1/s1600/mix_microgravity_manipulating_materials.jpg" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgCz4vqaA8vRKTazlupqaS49fDVJLJqywXYt0vjXUvAdiwgDgPyFiyTBjkxdKmkPSK8VjNa1jwGHA0PKzbVxkqIiidIPpiVhPiJWmLam0psMn3NosB1ZM8So2lShNhxqq8QCJLrN5oMsOn1/s1600/mix_microgravity_manipulating_materials.jpg" /></a></div>
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<br />
UAB-developed hardware from space shuttle missions in 1992 and 1995 is part of the "Moving Beyond Earth" gallery at the Smithsonian's Air and Space Museum. The equipment was first flown aboard the space shuttle Columbia from June 25-July 9, 1992, in the first flight of the U.S. Microgravity Laboratory-1. UAB's Larry DeLucas, who is principal investigator of the research now taking place at ISS, was a payload specialist on the 1992 flight.<br />
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEg9zIPOFO2CimjFUKfUzoelQZOjGVuLfHbs5dMhRIIxeyHYjjf6nlBg-mbOWwHO_7OGAdGiBDArp7OMylrAD7AI3VzirsOK023Hc_Mv8fGpLLDrBvi3sOTiAX3gdbk3betInLa3zczkJWO3/s1600/mix_micrgravity_macromolecular.jpg" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEg9zIPOFO2CimjFUKfUzoelQZOjGVuLfHbs5dMhRIIxeyHYjjf6nlBg-mbOWwHO_7OGAdGiBDArp7OMylrAD7AI3VzirsOK023Hc_Mv8fGpLLDrBvi3sOTiAX3gdbk3betInLa3zczkJWO3/s1600/mix_micrgravity_macromolecular.jpg" /></a></div>
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Learn more about the exhibit <a href="http://airandspace.si.edu/exhibitions/moving-beyond-earth/">here</a>, and find out more details on research in UAB's <a href="http://www.uab.edu/cbse/">Center for Biophysical Sciences and Engineering here</a>.<br />
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhZvni6J9A3rLcBCQMy8WWkrhpAamxdiiAKIRuxT3VyL8S5ZqOA8K7THEtvvcU_rIIRhf-z-8h4GK9It9Nqs-R9mWw3C05Xpok9Qcu5C9QnftTYkmSeMwAcJiiYYO4qHpIwLpdvN5URi3hf/s1600/mix_microgravity_glovebox.jpg" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhZvni6J9A3rLcBCQMy8WWkrhpAamxdiiAKIRuxT3VyL8S5ZqOA8K7THEtvvcU_rIIRhf-z-8h4GK9It9Nqs-R9mWw3C05Xpok9Qcu5C9QnftTYkmSeMwAcJiiYYO4qHpIwLpdvN5URi3hf/s1600/mix_microgravity_glovebox.jpg" /></a></div>
<br />Unknownnoreply@blogger.com0tag:blogger.com,1999:blog-4162601566541462615.post-12472487378345734392014-04-15T14:01:00.001-07:002014-10-08T09:55:55.590-07:00Cable guys: Inside UAB's high-tech, custom-built approach to eye science<div style="text-align: left;">
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<tr><td style="text-align: center;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjgx_5Kt-fWzgvm08LSiYHqgMitTL_gszY7fCzA9xSvi2aouXU4HkfVc7LWtDeNvV-jTUdiLesRfKGw2HgNsOD3ixjXNrGg7M8tFhb9cXEAUwmN_ZNtSxMFZO3KnLQj0uv-6lW5ec1aGWr7/s1600/mix_sm_air-serve-valve-photo-parts.jpg" imageanchor="1" style="margin-left: auto; margin-right: auto;"><img border="0" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjgx_5Kt-fWzgvm08LSiYHqgMitTL_gszY7fCzA9xSvi2aouXU4HkfVc7LWtDeNvV-jTUdiLesRfKGw2HgNsOD3ixjXNrGg7M8tFhb9cXEAUwmN_ZNtSxMFZO3KnLQj0uv-6lW5ec1aGWr7/s1600/mix_sm_air-serve-valve-photo-parts.jpg" /></a></td></tr>
<tr><td class="tr-caption" style="text-align: center;">This machine, designed and built by UAB vision researcher Crawford Downs, is producing ultra-clear images of a key structure implicated in glaucoma, the world's second leading cause of blindness. See the machine in action in a video below.</td></tr>
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<b><br />
</b> <b><span style="font-size: large;">The miracle of sight</span> </b>relies on a masterpiece of wiring. More than a million individual nerve cells scattered around the eye convert visual information into electricity. Then these individual cells are bundled together at the back of the eye into the optic nerve, which carries the signal to the brain.<br />
<br />
Problems with this central cable are at the root of glaucoma, the world's second leading cause of blindness, after cataracts. The underlying causes of this optic nerve deterioration are still poorly understood. But a pioneering group of researchers and clinicians at UAB are exploring a new paradigm that could revolutionize our understanding of glaucoma and other eye conditions, including myopia and keratoconus.<br />
<br />
The approach, known as ocular biomechanics, applies engineering principles to the eye. By creating detailed models of key eye structures, then stress-testing them in computer simulations, the scientists aim to identify the features of individual eyes that lead to glaucoma.<br />
<br />
The work is led by J. Crawford Downs, Ph.D., vice chair of basic science research in the UAB Department of Ophthalmology and director of the new <a href="http://www.uab.edu/medicine/ophthalmology/research-areas/ocular-biomechanics">UAB Ocular Biomechanics and Biotransport Program</a>, and Christopher Girkin, M.D., chair of the <a href="http://www.uab.edu/medicine/ophthalmology/">UAB Department of Ophthalmology</a>. It has attracted the attention of the National Eye Institute, which awarded Downs and Girkin a $1.125-million grant in early 2013.<br />
<br />
<b>Zooming In on Glaucoma</b><br />
Downs' efforts are focused on the lamina cribrosa, which acts as a mechanical seal at the optic nerve head where the optic nerve passes out of the back of the eye on its way to the brain. "The optic nerves go through pores in that structure," Downs explains. "It's also the place where the nerves get damaged in glaucoma. We want to understand the mechanics of the lamina cribrosa and what it looks like in three dimensions. That’s a key to understanding glaucoma biomechanics."<br />
<br />
The problem is that this tiny structure—"it's about the size of a pencil lead," Downs explains—doesn't respond well to conventional microscopic imaging techniques. "Every time you put a section of the tissue on a slide for imaging, it's always warped or folded or stretched, so you can’t stack up successive images into a 3D structure" Downs says. So he built his own machine to do the job.<br />
<i><br /></i>
<i>(See video below.)</i><br />
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<iframe allowfullscreen="" frameborder="0" height="315" src="//www.youtube.com/embed/abkXP5UYFmM" width="560"></iframe><br />
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This “fluorescent three-dimensional histologic reconstruction device” slices away tissue 1.5 micrometers at a time (about 1/100th the diameter of a human hair), snapping high-resolution pictures of the remaining tissues as it goes. With a volumetric resolution about 5 million times better than the best MRI, "I can see cell bodies with this technique," Downs says.<br />
<br />
He reveals an engineer's pride in the clever details of his creation. For instance, the device automatically e-mails him a picture every 100 frames and texts him if it runs into problems. That way he can monitor the process remotely and allow the machine to run 24 hours a day. "There are only two in the world—the one here at UAB for eyes and one we built for colleagues at Imperial College London to study osteoarthritis in mouse knees," Downs says.<br />
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<tr><td style="text-align: center;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEh3SKnguXQxFe66m2dFlsBxOiLxT-4Z302EqiFIAI4kz-NVspU8y1wTFk9_0tU1qNqAUlJytURynHVaVGw7CCQJVw_CWZgqzi9ek9pFUIgCng_u4N9jB3Yg3AiOUqvPLhwwPxfk2j2XOyve/s1600/sm_mix_cutter_image.jpg" imageanchor="1" style="margin-left: auto; margin-right: auto;"><img border="0" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEh3SKnguXQxFe66m2dFlsBxOiLxT-4Z302EqiFIAI4kz-NVspU8y1wTFk9_0tU1qNqAUlJytURynHVaVGw7CCQJVw_CWZgqzi9ek9pFUIgCng_u4N9jB3Yg3AiOUqvPLhwwPxfk2j2XOyve/s1600/sm_mix_cutter_image.jpg" /></a></td></tr>
<tr><td class="tr-caption" style="text-align: center;">An individual image from Downs' machine</td></tr>
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<b>Image to Insights</b><br />
Downs's first 3D rendering of the lamina, built from around 1,500 individual images, is just the beginning. Because everyone's lamina cribrosa is different, he is building a library of digitized models of laminas from the eyes of patients with and without glaucoma, as well as laminas from patients of different ages and ethnicities. "We can put the models in a computer, apply pressure to them, and simulate what happens mechanically," Downs says.<br />
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<tr><td style="text-align: center;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEidGLUcIXc_XlqLAlvx_gO52dmZJkwcqTu2pcXTm7edrwfGJpLkMRhWIR-KMf6SDijvIpsIzqAvvS0m8DSOrTuo1N00yvjYPoBVzyZns1CC9omoZQwmEWknRb_FpWIKuXlhRcsOEqRgz4lw/s1600/mix_26R_Screenshot_Anterior_300dpi.jpg" imageanchor="1" style="margin-left: auto; margin-right: auto;"><img border="0" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEidGLUcIXc_XlqLAlvx_gO52dmZJkwcqTu2pcXTm7edrwfGJpLkMRhWIR-KMf6SDijvIpsIzqAvvS0m8DSOrTuo1N00yvjYPoBVzyZns1CC9omoZQwmEWknRb_FpWIKuXlhRcsOEqRgz4lw/s1600/mix_26R_Screenshot_Anterior_300dpi.jpg" /></a></td></tr>
<tr><td class="tr-caption" style="text-align: center;">3D rendering of the lamina cribrosa</td></tr>
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Downs was one of the first biomedical engineers to take up the study of the eye; now he is making UAB the hub of the rapidly growing field of ocular biomechanics. He has already recruited a team of fellow bioengineers to tackle complex problems in glaucoma and other eye diseases. Raphael Grytz, Ph.D., is studying the growth and remodeling of the sclera and lamina cribrosa; Massimo Fazio, Ph.D., is developing new, ultra-precise tools to measure scleral deformations with pressure and track deformations in images; and Vincent Libertiaux, Ph.D., is simulating how the optic nerve head reacts to different intraocular pressures. "We're one of the biggest groups in the world," Downs says.<br />
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<tr><td style="text-align: center;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhGtSLxyuAMKnNXrX3gjLP0qZOoByT8CdqCprzLu1T9bjOAhQkp71DmevrUtzod4U2J1lY7MJudEPz6I_6-Omd4D1arL8qLRcGeSHD9FtCexCqQxP-C7IlsE_kbwl8RztrZQJCjo9jgtXqI/s1600/mix_sm_downs_team.jpg" imageanchor="1" style="margin-left: auto; margin-right: auto;"><img border="0" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhGtSLxyuAMKnNXrX3gjLP0qZOoByT8CdqCprzLu1T9bjOAhQkp71DmevrUtzod4U2J1lY7MJudEPz6I_6-Omd4D1arL8qLRcGeSHD9FtCexCqQxP-C7IlsE_kbwl8RztrZQJCjo9jgtXqI/s1600/mix_sm_downs_team.jpg" /></a></td></tr>
<tr><td class="tr-caption" style="text-align: center;">Left to right: Massimo Fazio, Crawford Downs, Vincent Libertiaux, and Raphael Grytz</td></tr>
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<b>Defining Disparities</b><br />
The gulf between surgeons and basic scientists isn't so wide in a specialty such as ophthalmology, where clinicians are used to doing their diagnosis at the tissue level. "I like to say that ophthalmologists are in vivo histopathologists," Girkin says.<br />
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Girkin's research is focused on health disparities in glaucoma, particularly in identifying why African Americans are at increased risk. Research by Downs and Girkin has helped uncover "some fundamental structural differences between the eyes of individuals with sub-Saharan African ancestry and those of individuals with European ancestry that may account for this elevated risk of glaucoma," Girkin says. "If we can define these differences we can target not just African Americans but anyone who is going to get glaucoma."<br />
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This basic research complements UAB's glaucoma service, which is among the nation’s busiest, Girkin notes. In addition to evaluating new treatment options, including laser therapy and minimally invasive surgeries, “our clinical research is looking at detection methods to allow us to find glaucoma earlier than ever, along with discovering novel pathways to treat this blinding disease," Girkin says.<br />
In a pilot program led by Girkin, UAB's Department of Ophthalmology has installed sophisticated imaging devices in the offices of two central Alabama independent optometrists who are located adjacent to Walmart Vision Centers, with a centralized image-reading center housed at UAB.<br />
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<i>(Learn more about the program in the video below.)</i><br />
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<iframe allowfullscreen="" frameborder="0" height="315" src="//www.youtube.com/embed/DxIc3C0YK8k" width="560"></iframe><br />
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</b> <b>Toward Early Detection</b><br />
The optical coherence tomography machines provide high-resolution images of the back of the eye. An optometrist can detect the earlier stages of glaucoma in those images, even before symptoms appear. Images of a patient’s eyes are electronically transmitted from the imaging machines at the optometrist’s office to the UAB center for confirmation of the diagnosis. UAB’s trained glaucoma specialists can then confer with the optometrist on complex cases to determine an appropriate treatment regimen. Patients who undergo the glaucoma testing also receive a dilated comprehensive eye exam and educational materials about glaucoma.<br />
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“This is an excellent example of the value of translating technology that has been evaluated and fine-tuned in the research setting and employing it in the field for the betterment of patients,” Girkin says. “This provides better access to care and better delivery of care within these hard-to-reach populations.”<br />
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The ultimate goal is to develop a noninvasive, image-based test "that a clinician can do in five minutes," Downs says. A human trial is at least a decade away, he predicts, but success would bring dramatic benefits: "You could cut the costs of treating glaucoma in half," saving billions of dollars per year.<br />
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<b>Learn More</b><br />
<a href="http://www.uab.edu/medicine/ophthalmology/">UAB Department of Ophthalmology</a><br />
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<a href="http://www.uab.edu/medicine/ophthalmology/research-areas/ocular-biomechanics">Ocular biomechanics at UAB</a><br />
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<a href="http://www.uab.edu/medicine/ophthalmology/research-areas">Research areas, UAB Department of Ophthalmology</a>Unknownnoreply@blogger.com0