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Gary S. Firestein, M.D.
Dr. Firestein’s laboratory helped define the synovial cytokine profile of rheumatoid arthritis (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. Dr. Firestein has also 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. His studies have validated many of therapeutic targets, several of which now have compounds in development (e.g., JNK, p38, MKK3, and IKK2) In addition to evaluating the structure and function of MAP kinases in the synovium, he also helped define the role of p38 MAP kinase in the spinal cord as a regulatory mechanism in peripheral inflammation and chronic pain states. Dr. Firestein has received the two highest international rheumatology awards for his research on the pathogenesis of RA, the Carol Nachman Prize in 1998 and the Lee C. Howley, Sr. Prize in 2006. His laboratory has trained numerous scientists, including three department heads in academia and one department head in industry. Trainees will be able to engage in a number of studies involving changes in gene and protein expression in in vitro and in vivo preparations.
Selected Publications
Hammaker DR, Boyle DL, Inoue T, Firestein GS. Regulation of the JNK pathway by TGF-beta activated kinase 1 in rheumatoid arthritis synoviocytes. Arthritis Res Ther 9:R57, 2007
Sweeney SE, Mo L, Firestein GS. Antiviral gene expression in rheumatoid arthritis: role of IKKepsilon and interferon regulatory factor 3. Arthritis Rheum 56:743-752, 2007.
Inoue T, Hammaker D, Boyle DL, Firestein GS. Regulation of JNK by MKKin fibroblast-like synoviocytes. Arthritis Rheum. 54:2127-2135, 2006.
Inoue T, Boyle DL, Corr M, Hammaker D, Davis RJ, Flavell RA, Firestein GS. Mitogen-activated protein kinase kinase 3 is a pivotal pathway regulating p38 activation in inflammatory arthritis. PNAS 14:5484-5489, 2006.
Cha HS, Rosengren S, Boyle DL, Firestein GS PUMA regulation and proapoptotic effects in fibroblast-like synoviocytes. Arthritis Rheum 54:587-592, 2006
Inoue T, Hammaker D, Boyle DL, Firestein GS. Regulation of p38 MAPK by MAPK kinases 3 and 6 in fibroblast-like synoviocytes. J Immunol. 174:4301-4306, 2005.