Arthritis/Immunology Unit (111R)
VA Medical Center
4150 Clement Street
San Francisco, CA. 94121

phone: 415-750-2104
fax: 415-750-6920
email: wofsyd@medsch.ucsf.edu

Dr. Wofsy received his undergraduate degree from Harvard (1968), his MD from the University of California, San Diego (1974), and his medical residency training and rheumatology fellowship training from the University of California, San Francisco. He joined the faculty in the Division of Rheumatology in 1980. In addition to his work as a Professor in the Rheumatology Division, Dr. Wofsy serves as Associate Dean of Admissions for the UCSF School of Medicine. Dr. Wofsy is a past-President of the American College of Rheumatology. He has served on numerous NIH study sections, and on the Arthritis Advisory Committee of the Food and Drug Administration.

Research Interests

Dr. Wofsy's research program is devoted to the development of novel therapies for autoimmune diseases, particularly systemic lupus erythematosus (SLE). For many years, his research focused on the cellular and molecular mechanisms that lead to autoimmunity in murine models for SLE. Based on this work, Dr. Wofsy and his colleagues proposed and tested several new therapeutic strategies in murine lupus. These strategies are directed against molecules that are expressed preferentially on the surface of activated lymphocytes or antigen-presenting cells (APC). By inhibiting primarily activated cells, these therapies are designed to block pathologic immune responses without damaging the entire immune system.

One of the new therapies that was pioneered by Dr. Wofsy's group involves the B7 family of molecules on APC. These molecules play a pivotal role in the generation of T-cell help. Specifically, the interaction of B7 molecules on APC with their ligand (designated CD28) on T cells provides an important signal for T-cell activation. Dr. Wofsy first showed that selective inhibition of the B7-CD28 interaction retards autoimmunity in murine lupus. He subsequently showed that this beneficial effect could be enhanced substantially in two ways: (i) by combining blockade of B7-CD28 with blockade of other receptor-ligand pairs (CD40-CD40L) on the surface of T cells and APC; and (ii) by combining blockade of B7-CD28 with cyclophosphamide therapy, the current gold standard for the treatment of lupus nephritis in people. In each case, combination therapy provided a prolonged benefit without sustained generalized immune suppression. This work has laid the foundation for translational studies designed to test new therapeutic strategies in people. Accordingly, Dr.Wofsy's current research involves translational clinical trials in people with SLE. This work has led to the establishment of a national Lupus Clinical Trials Consortium in which Dr. Wofsy serves as Scientific Director.

Publications

Finck BK, Linsley PS, Wofsy D. Treatment of murine lupus with CTLA4Ig. Science 265:1225-1227, 1994.

Daikh DI, Finck BK, Linsley, PS, Hollenbaugh D, Wofsy, D. Long-term inhibition of murine lupus by brief simultaneous blockade of the B7/CD28 and CD40/gp39 costimulation pathways. J Immunol 159:3104-3108, 1997.

Daikh DI, Wofsy D. Reversal of murine lupus nephritis with CTLA4Ig and cyclophosphamide. J Immunol 166:2913-2916, 2001.

Kalunian KC, Davis JC, Merrill JT, Totoritis MC, Wofsy D. Treatment of systemic lupus erythematosus by inhibition of T-cell costimulation with anti-CD154. Arthritis Rheum 46:3251-3258, 2002.

Wofsy D. Living in a Different World. Arthritis Rheum 52:395-401, 2005.

Daikh DI, Gillis J, Wofsy D: Inhibition of T cell costimulation: an emerging therapeutic strategy for autoimmune rheumatic diseases.  Arthritis Rheum 55:322-324, 2006.

Dall’Era M, Wofsy D: Clinical trial design in systemic lupus erythematosus. Curr Opin Rheumatol 18:476-480, 2006.

Dall’Era M, Chakravarty E, Wallace W, Genovese M, Weisman M, Kavanaugh A, Kalunian K, Dhar P, Vincent E, Pena-Rossi C, Wofsy D: Reduced B lymphocyte and immunoglobulin levels after atacicept treatment in patients with systemic lupus erythematosus.  Results of a multicenter, phase Ib, double-blind, placebo-controlled, dose-escalating trial.  Arthritis Rheum 56:4142-4150, 2007.

Sinclair A, Appel G, Dooley MA, Ginzler E, Isenberg D, Jayne D, Wofsy D, Solomons N: Mycophenolate mofetil as induction and maintenance therapy for lupus nephritis: rationale and protocol for the randomized, controlled Aspreva Lupus Management Study (ALMS).  Lupus 16:972, 2007.