Immunogenomics advances point to new biomarkers, therapies

Next-generation gene-sequencing technology 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 HudsonAlpha Institute for Biotechnology and Science magazine for researchers studying the interaction between genes and the immune system. The event was sponsored in partnership with UAB and its Comprehensive Arthritis, Musculoskeletal and Autoimmunity Center (CAMAC).

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.

“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 Division of Clinical Immunology and Rheumatology 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.”

From Associations to Biomarkers

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.

"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."

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.

Epigenetics and Therapeutics

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 UAB Center for Clinical and Translational Science. 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.

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.

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.

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.

Profiling Immune Signatures

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.

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.

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 Repertoire10K, 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.

Team-based Science

Collaborations between investigators at HudsonAlpha and UAB have taken place since the institute first opened in 2008, Kimberly says. But the new UAB–HudsonAlpha Center for Genomic Medicine, launched this summer, will increase these research partnerships and speed new discoveries in immunology, cancer, cardiovascular disease and many other fields, he notes.

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.

That’s why UAB is also creating a new Informatics Institute. It will work in tandem with the UAB–HudsonAlpha Center for Genomic Medicine and a third initiative, the UAB Personalized Medicine Institute, to build the infrastructure and recruit the data scientists needed to succeed in this new era of research.

“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.”

Advice for scientists from a Nobel Prize winner

The UAB School of Medicine recently played host to its leading regional forum, the Spring Immunology Symposium. Proof of the event's growing influence can be seen in  this year's keynote, Nobel Prize Laureate Rolf Zinkernagel, M.D., Ph.D., Professor in the Institute of Experimental Immunology at the University of Zurich. Dr. Zinkernagel won in his Nobel prize in 1996 for discoveries that helped to explain how the human immune system recognizes that one of its cells has been infected by a virus.

Included here is a brief video of Dr. Zinkernagel talking about his life's work, what young scientists should be thinking about and frontiers in immunology.



Dr. Rolf Zinkernagel, UAB Immunology Symposium, June 2013 from UAB School of Medicine on Vimeo.

Below is a summary of the video discussion in a Q&A format.

Q1. What should young people keep in mind who want to get into science and immunology?

• Success requires a scientist to be prepared for a ratio of 1 percent success to 99 percent failure and that a researcher perservere. 
• Young scientists should be prepared to work long hours because "the harder you work the luckier you get,"  
• It is important to find a research subject that you feel is extremely important and one where you burn to know the answer.  

Q2. What were the key decisions that led you to success in your field?

• Among Dr. Zinkernagel's important early decisions as a scientist was to first become a medical doctor. It enabled him to learn study a complex bodily system, the immune system, in its entirety as a foundation. 
• Dr. Zinkernagel started as a surgeon, but then got interested in immunology because of the immune rejections seen with transplanted organs. His focus remained on infectious disease from there on out, and not entirely by design.

Q3. What are your thoughts about how science differs around the word (e.g. in the U.S. versus Europe)?

• The United States, and the UK as well, treat research like a sport in some ways, with a spirit of "fierce, competitive openness" that gives new researchers an opportunity to show what they can do, and with relatively few restrictions. Of his native Switzerland, Dr. Zinkernagel said it has a good research environment, but its small size limits opportunities when compared to larger nations. 
• He also lauded the opportunistic outlook of the average American. That becomes important as researchers face seemingly unsolvable science problems, but just keep trying. 

Q4. What will the future of immunology look like?

• The next few years will see scientists gain a more and more detailed understanding of the processes and pathways involved in the immune system. He said that the field may go so deep that it identities a set of uniform processes because, at the root of everything, cells are cells despite their different functions.  
• That said, how cells and organs interact, the province of systems biology, still has a long way to go before researchers understand the sum of complex interactions that result in health or disease.
• In addition, immunology is a relatively "soft" science compared to physics, said Dr. Zinkernagel. There are yet many unknowns and presumptions that persist despite a lack of evidence to back them up, and many will turn out to be wrong. In that light, those involved in teaching the next generation of immunologists should take care to instill a combination of open-mindedness and critical thinking in their students.   

For a look back, here is another video created by Nobelprize.org after Dr. Zinkernagel won his award.

Key to immunogenomics value: embed research in healthcare system

Here we present the fourth interview in our podcast series focused on immunogenomics, a field is using new genomics tools to unravel the complexity of the human immune system and related diseases.

We recorded interviews with nationally recognized experts in this area from UAB, Harvard, Stanford and the National Institutes of Health at a recent immunogenomics symposium organized jointly by the HudsonAlpha Institute for Biotechnology and leading medical journal Nature Immunology. The symposium was sponsored in part by UAB and its Center for Clinical and Translational Science.

Our guest for this podcast is meeting presenter Robert Plenge, M.D., Ph.D., assistant professor of Medicine at Harvard Medical School – and Director of Genetics and Genomics within the Division of Rheumatology, Immunology and Allergy at Brigham and Women’s Hospital.

We discussed how immunogenomics has provided a flood of new clues about the genetic quirks contributing to many diseases, but the field must now, with the quirks as a guide, delve back into cells to learn the details of how such changes cause disease. To do so, they must collect human cells from patients known to have a given disease, and related efforts will accelerated the trend toward "embedded" genomics research.



Show notes for the interview:

1:01 Genomics is the study of DNA, RNA and the proteins that code for and how they contribute to health and disease. Immunology is the study of how several cell types fight infection, and why they attack our own tissues in some case to cause inflammation as part of inflammatory and autoimmune diseases. Immunogenomics then is the study of how these components work together, the genetic programming of the immune cell sets.

1:54 Plenge's work focuses on determining the genetic basis of predisposition for autoimmune diseases, and for rheumatoid arthritis in particular. Past genomic studies have determined some of the genes that contribute risk for rheumatoid arthritis, but immunogenomic studies are going further to determine the effect that genetic variations are having in cells, and at what that says about disease mechanisms.

3:19 The last few years have seen the rise of genome-wide association (GWAS) studies, where researchers use genomic technologies to examine every coding unit in the entire genomes of two sets of people (one with a disease, one without) to reveal every small genetic difference. They use tool called microarrays to look at large numbers of genetic sequences all at once, and to find small variations called single nucleotide polymorphisms (SNPs) associated with any given disease.

3:35 But GWAS studies only show that certain families have certain genetic variations that make them more susceptible to certain disease. They do not tell how or why the variations cause disease.  The next step then for Plenge and others will be to roll up their sleeves, go into the lab with this GWAS information and study the cells of people with disease-causing genetic variations to reveal disease mechanisms that can be countered with precision designed therapies.

4:29 Plenge's presentation talks about the importance of biomarkers, the physical measures that show a disease is underway or that a drug is countering it.. These are the tests that give meaning to clinical trial results. Researchers hope that new biomarkers will help them predict who will respond to a given treatment for rheumatoid arthritis based on their immunogenomic profile.

5:12 Plenge is working with the Pharmacogenomic Research Network (PGRN), organized by the National Heart Lung and Blood Institute, part of the Institutes of Health, to see if genomic patient profiles can be used to predict which patients are likely to respond, for instance, to an important category of treatments for rheumatoid arthritis called anti-TNF biologic drugs.

5: 47 It may be that most clinical trials will soon come to benefit from the addition of immunogenomic tools that predict any given patient's response to treatment, or their likelihood to experience a given complication of side effect.

6:22  It's easy to think of the immune system as involved in fighting infection, or even in autoimmune diseases like rheumatoid arthritis where the system mistakenly recognizes its own tissue as foreign and attacks it. Mounting evidence argues, however, show that "mistakes" by the immune system bring about inflammation at the root of cardiovascular disease, neurodegeneritive conditions, cancer, pulmonary disease, etc. A profound understanding of the interplay between genomics and immunology will offer tremendous opportunities to develop new therapies, says Plenge.

7:25 Immunogenomics may help to lessen the massive time and cost necessary today to conduct the average clinical trial. Plenge hopes that emerging techniques and advances will create efficiencies in medical research.  Treatments that address inflammation in rheumatoid arthritis may also prove to have utility in reducing inflammation contributing to say diseased arteries. The potential for this becomes greater the more profound the field's understanding of genomic/immune system interplay.

9:27 Many of the past studies in immunology and genomics were done in mice meant to serve as models of human disease.  But mice are different than humans. There are now many more opportunities to do what Plenge calls "embedded immunogenomics," where registries collect cells and data from human patients for study as part of routine clinical care.  The research is embedded in the healthcare system. If patients consent for a quick blood draw, researchers gain access to details of subsets of cells and genes linked to diseases, and can follow changes over time.

11:13  One emerging trend may be the uncoupling of such genetic registries from a doctor's office visit. People participating in the new registries may just stop by a lab (e.g. Quest Diagnostics) for testing whenever they don't feel well.

12:20 Plenge recommends that researchers interested in learning more about this area look into a database under development called Immunobase, which is working to catalog inherited genetic variations contributing to a wide variety of diseases. The work underway at Sage Bionetworks and  i2b2 (informatics for integrating biology and the bedside), an NIH-funded biocomputing initiative, represent other interesting initiatives. Patients interested in participating in research might look up 23andMe, and those with rheumatoid arthritis, the Arthritis Internet Registry.

Tune in next Friday to hear our talk with John O’Shea, M.D., chief of the Molecular Immunology and Inflammation Branch with the National Institute of Arthritis and Musculoskeletal and Skin Diseases, part of the National Institutes of Health.

Human immuno-genome interview series: UAB's Casey Weaver

Most of the time The Mix covers general research topics, but for the next several Fridays we will feature a podcast series focused on the emerging field of immunogenomics.

We recorded the interviews live at a recent immunogenomics symposium organized jointly by the HudsonAlpha Institute for Biotechnology and leading medical journal Nature Immunology. The symposium was sponsored in part by UAB and its Center for Clinical and Translational Science.

Immunogenomics as a field is using new genomics tools to unravel the complexity of the human immune system and related diseases, which are now known to include heart disease, neurological disease and cancer because of their interplay with inflammation. The work promises to improve diagnostic tools and offer new treatment approaches.

Among the most important of genomics tools are microarrays, which enable researchers to measure the expression levels of many genes at once, and bioinformatic programs, which identify patterns in the massive data sets generated during genomic analysis of individuals and populations.

Our guest for this podcast is meeting presenter Casey Weaver, M.D. professor in the Department of Pathology within the UAB School of Medicine. We discussed how immunogenomic tools have helped researchers to finally grapple with and begin to dissect the complex workings of the immune system, and specifically, of T cells.


Show notes from the podcast:

:57 Our view off the immune system has been zooming in for years, from early studies that looked at the system at the cellular level, to studies that examined the relevant molecules inside cells, and now, to studies looking at the genes that control it.

2:00 Weaver's team has been trying to understand how T cells, one of the workhorse cell types of the precise, thorough and massive adaptive immune response, are controlled by genes that code for cytokines, signaling proteins that ramp the immune response up and down as needed. The team is also interested in the process by which more stem-cell-like T cells "decide" to become one of several more specialized cells, depending on the kind of bodily invader encountered.

2:24 CD4+ T cells are the "master regulators" of the immune response, and Weaver studies how these cells decide to mature into different types of immune cells depending on the kind of immune response needed. His work in recent years has been aimed at mapping the genes expressed in each scenario.

2:45 Weaver's team is working to genetically engineer mice in which researchers can see a readout of which genes are expressed in which immune cells and when. It has became clear how limited the current understanding is of how immune genes are controlled in T cells.

4:13 Every kind of microbial challenge (virus, bacterium, fungus) requires a different kind of immune response to eliminate it. CD4+ T cells differentiation adapts to each threat, matching up with so that it can oversee the right response.

5:11 Along with genes controlling T cell responses, there are often small pieces of genetic material that regulate when and where genes turn and of.  Weaver's team has spent time identifying several of the regulatory genetic elements that control T cell cytokine genes. Several of these elements are cis (lie alonside) the genes they control.  

5:51 Rapid advances in genomic data and technology have enabled researchers to establish correlations between small changes in genes, and in the regulatory elements that govern them, and susceptibility for many diseases.

6:19 How susceptible a given person is to an immune-mediated diseases may depend on small changes in certain genes, so-called single nucleotide polymorphisms or SNPs, but the field is not sure of their data.  Does a certain SNP cause disease, or is it just in the same region as something else that does?

6:59 One way to answer that question is to test the impact of a SNP in a live organism where the immune system is at work. Part of the strategy in Weaver's lab then has been to put part of a human cytokine gene with a SNP associated with a disease into a mouse model, and to see if it has the predicted impact.

8:15 Part of the difficulty of analyzing gene expression traditionally has been that transgenic techniques (putting human genes in a mouse) may end up putting that gene into the mouse genome in several places and randomly.  That makes it hard to pick up the subtle readouts you need to tell whether or not a SNP is contributing to a disease. Weaver's solution, one used by other labs as well, is to insert entire genes into the genome that include the SNP under study, in effect creating a level genetic playing field on which to judge the contribution of each SNP to disease.

11:06 Weaver recommends those interested in more information on the field see the National Center for Biotechnology Information and the UCSC Genome Browser.

Immunogenome meets computing power

Welcome to the second podcast in the new series from the Mix on the emerging field of immunogenomics.

I recorded the interviews on the subject with national experts from UAB, Harvard, Stanford and the NIH at a recent symposium organized by the HudsonAlpha Institute for Biotechnology and leading medical journal Nature Immunology. The symposium was sponsored in part by UAB and its Center for Clinical and Translational Science.

Immunogenomics is using new genomics tools to unravel the complexity of the human immune system and related diseases. Among the most important of genomics tools are microarrays, which enable researchers to measure the expression levels of many genes at once, and bioinformatic programs, which identify patterns in the massive data sets generated during genomic analysis.

Our guest for this podcast is meeting presenter Stephen Quake, D.Phil., professor in the Department of Bioengineering at Stanford and a Howard Hughes Medical Institute investigator. Quake specializes in microfluidic large-scale integration (LSI), in which he use his "lab on a chip" (a fluid-containing maze of channels, valves and wells on a microchip) to achieve high-speed, automated analysis of biological problems.

Our discussion covered how, by coming up with technologies that more precisely measure biological processes, the field has revealed new laws of nature at work in the body.


Show notes from the interview

:49 Immunogenomics, says Quake, can be defined as the sequencing and study of genes involved in the performance of the human immune system — genes whose expression pattern is in constant flux.

1:45 Right now you can't go to the doctor and ask him or her to give you a molecular diagnostic test measuring the health of your immune system, but such tests may be coming with the help of immunogenomics. In the future, such tests may be used in combination with therapies that adjust your immune response when it's too sensitive (autoimmune disease) or too weak (vulnerable to infectious disease).

2:52 Technology development is part and parcel with advances in immunogenomics. Quake's original training was in physics, with its 300-year tradition of precision measurement, which helped him to develop new measurement technologies for biological systems.

3:12 Biology was revolutionized time and time again in the 20th century by new technologies, from chromatography in the early part of the century to gene sequencing and genomic technologies in the latter half.

4:20 High-speed testing, or high-throughput technologies, have allowed for complex, massive experiments that could never have been conceived before their advent. The modern era is characterized by continual leaps in computing power, and that same type of technological scaling has now moved into the analysis of genomic information.

5:34 Computing power helps to resolve the complexity of the human immune system (now recognized as more complex than originally understood) and to pursue simple ideas.

5:59 The field of immunogenomics is young, perhaps starting with a zebrafish model paper out of Quake's lab in 2009. His early work in immunogenomics was focused on answering basic questions about the immune system, such as how many antibodies the human body contains.

7:13 The next big milestones in the field will include figuring out how to intrepret immunogenomic data in the context of a given event, like getting vaccinated or contracting an infectious disease. Lots of labs are working in this area, and it will be exciting as they reach their conclusions.

8:22 Immunogenomics is still focused on basic questions about how to measure the immune system with genomics tools. It will be some time before the field can launch an immune version of the Human Genome Project (the Human Immunogenome Project?).

9:03 With the field being so new, there our no textbooks on it nor are there yet review papers to recommend, although some are being written right now. For those with a deep interest, says Quake, the best course may be to search the literature by keyword using PubMed, and he invites all to look up his papers, which are listed by topic at his website.

About the podcaster:

Greg Williams @gregscience @themixuab is research editor at the University of Alabama at Birmingham. 

The first podcast in the immunogenomics series, which debuted on Oct. 5, 2012, featured S. Louis Bridges Jr., M.D., Ph.D., director of the Division of Clinical Immunology and Rheumatology within the UAB School of Medicine.

Tune in next Friday, when we will talk with symposium presenter Casey Weaver, M.D., professor in the Department of Pathology with the UAB School of Medicine.

New series on the human immunogenome

Most of the time The Mix covers general research topics, but for the next several Fridays we will feature a podcast series focused on the emerging field of immunogenomics. Guests will include nationally recognized experts in this area from UAB, HudsonAlpha, Harvard, Stanford and the National Institutes of Health.

We recorded the interviews live at a recent immunogenomics symposium organized jointly by the HudsonAlpha Institute for Biotechnology and leading medical journal Nature Immunology. The symposium was sponsored in part by UAB and its Center for Clinical and Translational Science.

Immunogenomics as a field is using new genomics tools to unravel the complexity of the human immune system and related diseases, which are now known to include heart disease, neurological disease and cancer because of their interplay with inflammation. The work promises to improve diagnostic tools and offer new treatment approaches.

Among the most important of genomics tools are microarrays, which enable researchers to measure the expression levels of many genes at once, and bioinformatic programs, which identify patterns in the massive data sets generated during genomic analysis of individuals and populations.

Our first guest in the series is S. Louis Bridges, Jr., M.D., Ph.D., director of the Division of Clinical Immunology and Rheumatology within the UAB School of Medicine and deputy director of the UAB Comprehensive Arthritis, Musculoskeletal, and Autoimmunity Center. Tune in next Friday, when we will talk with Stephen Quake, D.Phil., professor in the Department of Bioengineering at Stanford.




Show notes for the interview:

1:09 Immunogenomics can be defined as the use of the tools of genomics to study human immune cells, and to define the mechanism by which immune-related diseases damage the body. 

2:02 Rheumatoid arthritis is the most common autoimmune disease, in which immune cells called antibodies come to target the body's own tissues.

2:47 In many ways, RA represents a cogent example of the intersection between immunology and genomics in that about 30 percent of the risk for the disease is based on your genes. In addition, small changes in more than 35 different genes contribute to that risk.

3:39 Bridges and colleagues founded the CLEAR registry, which stands for Consortium for the Longitudinal Evaluation of African Americans with Early Rheumatoid Arthritis. The registry compares the incidence and severity of RA in African-Americans against other ethnic and racial groups over time to better understand how immune-system mechanisms cause damage. Past studies have found that RA is more severe in African-Americans than in whites.

4:42 Researchers are working to understand the genetic basis of RA severity in African-Americans in part by examining single genes (RANK ligand, peptidase) known to be associated with disease severity or early onset. Bridges and colleagues have also been conducting genome-wide association studies, which look at every piece of code making up every gene (nucleotide) in a group of people to identify the differences seen only in people with a certain condition. In many cases, such studies reveal that networks of genes contribute to a disease, as opposed to a problem with the code of any single gene.

5:40 All races share 80 to 90 percent of the genetic background leading to RA, so perhaps 2 to 5 percent of genes vary by race, says Bridges.

6:02 In some whites, a gene called PTP-N22, for instance, has randomly undergone a small change in its code called an SNP (single nucleotide polymorphism). People who happen to have that change in PTP-N22 are 1.9 times as likely to develop RA.

7:09 A change in a single piece of code out of 3 billion base pairs making up the human genome, if it's in the wrong spot, can contribute to either the incidence or severity of RA. Such changes may predict which patients will go on to see their joints destroyed.

7:56  Immunogenomics work will have its first impact in the clinic in the form of a new wave of identified biomarkers that predict which patients will do well on which treatments. Further down the road, Bridges sees the field identifying more specific subsets of cells most responsible for RA-related damage, which could in turn lead to the development of more targeted treatments.

9:44 Bridges recommends that members of the general public interested in learning more on RA and related research visit the Mayo Clinic's RA pages. Researchers may want to look up the work of Robert Plenge, M.D., Ph.D., assistant professor of medicine at Harvard Medical School, whose interview is coming up as part of this podcast series in a few weeks.

About the podcaster:

Greg Williams @gregscience @themixuab is research editor within Media Relations at the University of Alabama at Birmingham.