Research Update - December 2006

From the Chair, Medical & Scientific Advisory Council, Philip L. Cohen, MD

Every year, the Arthritis Foundation awards the Lee C. Howley Prize to recognize an outstanding contribution to research that represents a major advance in the understanding, treatment or prevention of arthritis and rheumatic diseases. The 2006 recipient of this honor is Gary S. Firestein, MD, of the University of California, San Diego. Gary began his investigations into the pathogenesis of rheumatoid arthritis in the 1980s. His innovative work led to fundamental changes in the way scientists understand inflammation and treat rheumatoid arthritis (RA).

It was in a landmark review article published in 1990 (see Identifying Cytokines in Rheumatoid Arthritis) that Gary identified three proinflammatory cytokines, IL-1, TNF-α and IL-6, as potential targets of therapy. That article gave visibility to this idea on which he and a few other groups were focused. The concept initially was met with considerable animosity and derision by the rheumatology community. But the combined work of these few labs started the revolution in anti-cytokine therapy – a revolution that led to the development of etanercept, adalimumab, infliximab and anakinra.

Gary continued to delve into the whys and hows of RA and wrote an article in 1997 that has been described as “provocative and original.” In that paper, he identified genetic mutations in synovial cells affected by RA – mutations that could alter the expression of cytokines. (See Mutations in Tumor Suppressor Gene in RA Synovium) for a summary of that paper.

In the mid-1990s, and continuing today, his team seeks to identify the role of MAP kinases in RA inflammation. In the article summarized in JNK Linked to Joint Destruction in RA, originally published in 2001, Gary and his team showed that inhibition of a particular MAP kinase called JNK could successfully treat arthritis in an animal model.

Gary received his first Arthritis Foundation grant in 1996. He was awarded a 2-year Biomedical Sciences Grant (BSG) that provided $75,000 per year; in 1999 he received a 3-year BSG for $90,000 per year. In 2006 he was awarded an Innovative Research Grant (IRG) for $100,000 per year for 2 years. The focus of his IRG is demonstrating how the central nervous system regulates inflammation in the joints. A summary of his recent work can be found in the Central Nervous System Regulation of Inflammation article.

When you talk to Gary about his accomplishments, he is always quick to point out that he does not work alone. “Of course it was a group effort involving many very talented people, especially my mentor Dr. Nathan Zvaifler and, more recently, my close collaborator David Boyle,” he says. He likewise praises the postdoctoral fellows and junior investigators he has mentored over the years.

I had the opportunity to catch up with one of Gary’s previous colleagues who has gone on to establish his own research lab at the University of Rochester in New York. Edward M. Schwarz, PhD, received a Postdoctoral Fellowship grant from the Arthritis Foundation in 1994–96 and worked in Dr. Firestein’s lab during that time. “Dr. Firestein was a great mentor to me when I was a postdoctoral fellow at the Salk Institute working in a molecular biology lab. He introduced me to the mouse models of arthritis that I still work on today. More importantly, he continued to mentor me after I started my own lab 2,500 miles away. His mentorship enabled me to get my first National Institutes of Health grant.” Of his Arthritis Foundation fellowship, he says “it steered me toward translational research. I learned how to interact with rheumatologists during my postdoc, and now, along with my basic science research, I run clinical programs aimed at understanding the pathogenesis of disease in patients with arthritis.” See Autoimmunity and Bone for a summary of the work that Dr. Schwarz is doing now in his own lab, thanks to the start he got from the Arthritis Foundation and Dr. Firestein. 

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