UCSD
Copyright 2005 UCSD Department of Medicine        * Rheumatology Section * Gary S. Firestein, M.D.
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Gary S. Firestein, M.D.
Professor of Medicine
Chief, Division of Rheumatology Allergy & Immunology
Dean, Translational Medicine
Gary S. Firestein, M.D.
9500 Gilman Drive, Room 5098
La Jolla, CA 92093-0656
Tel: (858) 822-0480
Fax: (858) 534-2606
E-mail: gfirestein@ucsd.edu
  Education 
  • 1976 - A.B. (Chemistry), Harvard College, Cambridge, MA
  • 1980 - M.D. (Medicine), Johns Hopkins U. School of Medicine, Baltimore, MD
  Employment 
  • 1980 - 1983: Resident in Medicine
    • UCLA Medical Center
  • 1983 - 1986: Fellow, Rheumatology Division
    • University of California, San Diego
  • 1986 - 1988: Fellow, Molecular Biology
    • La Jolla Cancer Research Institute
  • 1988 - 1992: Assistant Professor of Medicine in Residence
    • University of California, San Diego
  • 1992 - 1996: Senior Director, Immunology
    • Gensia, Inc.
  • 1996 - 1997: Associate Professor of Medicine
    • University of California, San Diego
  • 1997 - Present: Professor of Medicine
    • University of California, San Diego
  • 1998 - Present: Chief, Division of Rheumatology, Allergy, & Immunology
    • University of California, San Diego
  • 2000 - 2003: Member; Chairman (2001-03)
    • FDA Arthritis Advisory Committee, Washington, D.C.
  • 2003 - Present: Director
    • UCSD Clinical Investigation Institute
  • 2008 - Present: Dean
    • Translational  Medicine
  Board Certification 
  • Internal Medicine
  • Rheumatology
  Hospital Affiliations 
  • UCSD Thornton Hospital, La Jolla
  • UCSD Medical Center, Hillcrest
  Honors and Awards 
  • 1996: Elected to American Society for Clinical Investigation
  • 1998: Carol-Nachman Prize for Rheumatology
  • 2000: Ruitinga van Swieten Visiting Professor, University of Amsterdam
  • 2002: Elected to Association of American Physicians
  • 2002: Visiting Professor, and Physician-in-Chief Pro-Tempore, Hospital for Special Surgery, New York
  • 2003: Visiting Professor, Brigham and Women’s Hospital, Boston
  • 2004: Weischselbaum-Landsteiner Lecture, University of Vienna
  • 2006:  Lee C. Howley, Sr. Prize for Arthritis Research
  Research 
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.
  Publications 

(Publications selected from 223 manuscripts, chapters, and books)

 

1.     Firestein GS, F Echeverri, M Yeo, NJ Zvaifler, and DR Green. Somatic mutations in the p53 tumor suppressor gene in rheumatoid arthritis synovium. Proc Natl Acad Sci  94: 10895-10900, 1997.

 

2.     Firestein GS, and NJ Zvaifler.  Anticytokine therapy in RA. New Engl J Med 337:195-197, 1997.

 

3.       Aupperle K, DL Boyle, M Hendrix, NJ Zvaifler, M Barbosa, GS Firestein. Regulation of synoviocyte prolifera­tion, apoptosis, and invasiveness by the p53 tumor suppressor gene. Amer J Pathol 152:1091-1098, 1998.

 

4.       Nguyen K, DL Boyle, J McCormack, S Chada, DJ Jolly, and GS Firestein. Direct synovial gene transfer with retroviral vectors in rat adjuvant arthritis. J Rheumatol 25:118-125,1998.

 

5.       Han Z, DL Boyle, A Manning, and GS Firestein. AP-1 and NF-kB regulation in rheumatoid arthritis and murine collagen-induced arthritis. Autoimmunity 28:197-208, 1998.

 

6.       Han Z, DL Boyle, Y Shi, DR Green and GS Firestein. Dominant negative p53 mutations in rheumatoid arthritis. Arthritis Rheum 42:1088-1092, 1999.

 

7.       Aupperle KR, B Bennett, DL Boyle, PP Tak, AM Manning and GS Firestein. Regulation of NF-kB by IkB kinase in fibroblast-like synoviocytes. J Immunol 163:427-33, 1999.

 

8.       Han Z, DL Boyle, KR Aupperle, B Bennett, AM Manning, and GS Firestein. Jun N-terminal kinase activation in rheumatoid arthritis synoviocytes. J Pharm Exp Ther 291:124-130, 1999.

 

9.       Boyle DL, KHY Nguyen, S Zhaung, Y Shi, JE McCormack, S Chada, GS Firestein. Intra-articular IL-4 gene therapy in arthritis: anti-inflammatory effects and enhanced Th2 activity. Gene Ther, 6:1911-1918, 1999.

 

10.   Tak, PP, MS Klapwijk, SFM Broersen, DA van de Geest, MJ Overbeek, PK Robbins, and

      GS Firestein. Apoptosis and p53 expression in rat adjuvant arthritis. Arthritis Research,

      2:229-235, 2000.

 

11.   Gerlag DM, L Ransone, M Panki, Z Han, PP Tak, AM Manning, GS Firestein. Effect of a T cell specific NF-kB inhibitor on in vitro cytokine production and CIA in mice. J Immunol, 165:1652-1658, 2000.

 

12.   Aupperle KR, BL Bennett, Z Han, DL Boyle, AM Manning and GS Firestein. NF-kB regulation by IkB kinase-2 in fibroblast-like synoviocytes.  J Immunol, 166:2705-2711, 2001.

 

13.   Burger JA, NJ Zvaifler, N Tsukada, GS Firestein and TJ Kipps. Fibroblast-like synoviocytes support B-cell pseudoemperipolesis via a stromal cell-derived factor-1- and CD106 (VCAM-1)-dependent mechanism. J Clin Invest. 107:305-315, 2001.

 

14.   Han Z, DL Boyle, L Chang, B Bennett, M Karin, L Yang, AM Manning and GS Firestein. c-Jun N-Terminal kinase is required for metalloproteinase expression and joint destruction in inflammatory arthritis.  J Clin Invest. 108:73-81, 2001.

 

15.   Boyle DL, J Moore, L Yang, L Sorkin and GS Firestein. Stimulation of spinal adenosine receptors inhibits rat adjuvant arthritis. Arthritis Rheum 46:3076-3082, 2002.

 

16.   Firestein GS, and NJ Zvaifler. How important are T cells in chronic rheumatoid synovitis. II. T cell independent mechanisms from beginning to end.  Arthritis Rheum 46:298-308, 2002.

 

17.   Yamanishi Y, DL Boyle, Z Han, MJ. Pinkoski, A Mahboubi, T Lin, NJ Zvaifler, DR Green, and GS Firestein. p53 regulates apoptosis, synovitis and joint destruction in CIA. Amer J Pathol, 160:123-30, 2002.

 

18.   Han Z, L Chang, Y Yamanishi, M Karin and GS Firestein. Joint damage and inflammation in JNK2 knockout mice with passive collagen-induced arthritis. Arthritis Rheum 46:818-823, 2002.

 

19.   Yamanishi Y, DL Boyle, S Rosengren, DR Green, NJ Zvaifler, and GS Firestein.  Regional analysis of p53 mutations in rheumatoid arthritis synovium.  PNAS 99:10025-30, 2002.

 

20.   Firestein GS. Evolving concepts of rheumatoid arthritis. Nature, 423:356-361, 2003.

 

21.   Sundarrajan M,  DL Boyle, M Chabaud, D Hammaker and GS Firestein. Expression and regulation of the MAP kinase kinases, MKK4 and MKK7, in rheumatoid arthritis. Arthritis Rheum, 48:2450-60, 2003.

 

22.   Cramer T, Y Yamanishi, BE Clausen, I Forster, R Pawlinski, N Mackman, VH Haase, R Jaenisch, M Corr, V Nizet, GS Firestein, H-P Gerber, N Ferrara, RS Johnson. HIF-1a is essential for myeloid cell-mediated inflammation. Cell 112:645-57, 2003.

 

23.   Boyle DL, S Rosengren, A Kavanaugh, W Bugbee, and GS Firestein. Inflammatory biomarker analysis of synovium by quantitative real time PCR.  Arthritis Res Ther, 5:R352-360, 2003.

 

24.   Chabaud-Riou M, and GS Firestein. Expression and activation of MKK3 and MKK6 in rheumatoid arthritis. Amer J Pathol, 164: 177-84, 2004.

 

25.   Hammaker D, DL Boyle, MM Chabaud-Riou, and GS Firestein. Regulation of JNK by MEKK2 and MAP kinase kinase kinases in rheumatoid arthritis. J Immunol, 172:1612-1618, 2004.

 

26.   Hoffman HM, S Rosengren, DL Boyle, JY Cho, J Nayar, JL Mueller, JP Anderson, AA

      Wanderer, and GS Firestein. Interleukin-1 receptor antagonist prevents cold-associated

      acute inflammation in familial cold autoinflammatory syndrome. Lancet, 364:1779-85, 2004.

 

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

 

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

 

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

 

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

 

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

 

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

 

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

 

34.  Corr MP, DL Boyle, L Ronacher Uc, N Flores, and GS Firestein. Synergistic benefit and IFNßetargeting IKK in inflammatory arthritis. Ann Rheum Dis, 68:257-63, 2009.

 
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