Gary S. Firestein, MD

Gary S. Firestein, MD

Gary S. Firestein, M.D.
Distinguished Professor of Medicine
Dean and Associate Vice Chancellor of Translational Medicine
Director, Clinical and Translational Research Institute

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Dr. Firestein received his AB (chemistry) at Harvard College, Cambridge, MA.  He then received his MD (Medicine) at The Johns Hopkins University School of Medicine, Baltimore, MD.  He completed two fellowships, one in molecular biology at the Burnham Institute in La Jolla, CA, and one in rheumatology at the University of California, San Diego.

Research Interests

Dr. Firestein's research efforts have focused on the pathogenesis of rheumatoid arthritis (RA). His laboratory helped define the synovial cytokine profile of RA and demonstrated the dominance of macrophage and fibroblast products as opposed to the expected T cell cytokines. These studies contributed to the development of the highly effective anti-TNF approaches in RA. Recently, Dr. Firestein has focused his attention on synoviocyte transformation in RA as a mechanism of joint destruction. His group was the first to describe somatic mutations in the p53 tumor suppressor genes in the RA synovium. The mutations were subsequently demonstrated to be dominant negative and increased the cartilage invasiveness of these cells. Dr. Firestein's laboratory has also worked extensively on metalloproteinase and cytokine gene regulation in synoviocytes by MAP kinases and NF-kB as well as on novel gene therapy approaches to RA.

Clinic Focus

Rheumatic Diseases

Clinical Profile and Appointments

Clinic Practice Locations

Hillcrest Medical Offices South

Selected Publications

1. Hoffman HM, Rosengren S, Boyle DL, Cho JY, Nayar J, Mueller JL, Anderson JP, Wanderer AA, and Firestein GS. Interleukin-1 receptor antagonist prevents cold-associated acute inflammation in familial cold autoinflammatory syndrome. Lancet, 364:1779-85, 2004. PMCID: 15541451

2. Inoue T, Hammaker D, Boyle DL, and Firestein GS. Regulation of p38 MAPK by MAPK kinases 3 and 6 in fibroblast-like synoviocytes. J Immunol, 174: 4301-4306, 2005. PMID: 15778394

3. Inoue, T, Boyle DL, Corr M, Hammaker D, Davis RJ, Flavell RA, and Firestein GS. MKK3 is a pivotal pathway regulating p38 activation in inflammatory arthritis. Proc. Natl Acad Sci USA, 103:5484-9, 2006. PMCID: 1459381

4. Boyle DL, Jones TJ, Hammaker D, Svensson CI, Rosengren S, Mauyama K, Sorkin LS, and Firestein GS. Regulation of peripheral inflammation by spinal p38 MAP kinase in rats. PLoS Medicine, 3:1617-24, 2006. PMCID: 1175047

5. Sweeney S, Mo L, and Firestein GS. Anti-viral defense mechanisms in rheumatoid arthritis: Pivotal role for IKKe and IRF3. Arthritis Rheum, 56:743-52, 2007. PMID: 17328045

6. Hammaker DR, Boyle DL, Inoue T, and Firestein GS. Regulation of the JNK pathway by TGF-beta activated kinase 1 in rheumatoid arthritis synoviocytes. Arthritis Res Ther, 9:R57, 2007. PMCID: 2206340

7. Waldburger JM, Boyle DL, Pavlov VA, Tracey KJ, and Firestein GS. Acetylcholine regulates synoviocyte cytokine expression via the alpha7 nicotinic receptor, Arthritis Rheum, 58:3439-49, 2008. PMID: 18975306

8. Yoshizawa T, Hammaker D, Sweeney SE, Boyle DL, and Firestein GS. Synoviocyte innate immune responses: I. Differential regulation of interferon responses and the JNK pathway by MAP kinase kinases. J Immunol, 181:3252-8, 2008. PMCID: 2725405

9. Corr MP, Boyle DL, Ronacher L, Flores N, and Firestein GS. Synergistic benefit targeting IKKe and IFNß in inflammatory arthritis. Ann Rheum Dis, 68:257-63, 2009. PMID: 18653628

10. Svensson CI, Inoue T, Hammaker D, Fukushima A, Papa S, Franzoso G, Schett G, Corr M, Boyle DL, Firestein GS. Gadd45beta deficiency in rheumatoid arthritis: enhanced synovitis through JNK signaling. Arthritis Rheum. 60:3229-40, 2009. PMID: 19877043

11. Yoshizawa T, Hammaker D, Boyle DL, Corr M, Flavell R, Davis R, Schett G, and Firestein GS. Role of MAPK kinase 6 in arthritis: distinct mechanism of action in inflammation and cytokine expression. J Immunol. 183:1360-7, 2009. PMID: 19561096

12. Sweeney SE, Howard T, and Firestein GS. Synoviocyte innate immune responses: II. Regulation of interferon response genes by IRF3. J Immunol. 184:7162-8, 2010. PMCID: 20483755

13. Fukushima A, Boyle DL, Corr M, Firestein GS. Kinetic analysis of synovial signaling and gene expression in animal models of arthritis. Ann Rheum Dis. 69:918-23, 2010. PMID: 19473996

14. Guma M, Kashiwakura J, Crain B, Kawakami Y, Beutler B, Firestein GS, Kawakami T, Karin M, and Corr M. JNK1 controls mast cell degranulation and IL-1{beta} production in inflammatory arthritis. Proc Natl Acad Sci USA. 107:22122-7, 2010. PMID: 2113522

15. Luo Y, Boyle DL, Hammaker D, Edgar M, Franzoso G, and Firestein GS. Suppression of collagen-induced arthritis in growth arrest and DNA damage inducible 45β (Gadd45β)-deficient mice. Arthritis Rheum. 2011 Jun 23. [Epub ahead of print]. PMID: 21702006

Additional Firestein Publications via PubMed