David Wofsy, MD

Professor

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 UCSF faculty in 1980. He currently Professor of Medicine and Microbiology/Immunology at UCSF. Dr. Wofsy also serves as Associate Dean for Admissions for the UCSF School of Medicine. He has served on numerous NIH study sections, and on the Arthritis Advisory Committee of the Food and Drug Administration. Dr. Wofsy is a past-President of the American College of Rheumatology.

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. These therapies are designed to block pathologic immune responses without damaging the entire immune system. One of the therapies that was pioneered by Dr. Wofsy's group involves the B7 family of molecules on antigen-presenting cells (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. In each case, combination therapy provided a prolonged benefit without sustained generalized immune suppression. This work laid the foundation for translational studies that resulted in FDA approval of a new treatment for rheumatoid arthritis. Dr.Wofsy's current research is focused on establishing whether this therapy can be life-saving in people with kidney disease due to SLE.
Education
2017 - Diversity, Equity, and Inclusion Champion Training, University of California
Residency, - School of Medicine, University of California, San Francisco
Honors and Awards
  • Master of the American College of Rheumatology, American College of Rheumatology, 2012
  • Paul Klemperer Award and Medal, New York Academy of Medicine, 2011
  • Lee C. Howley Sr. Prize, Arthritis Foundation, 2007
  • Arthritis Hero Award, Arthritis Foundation, 2001
  • Edmund L. Dubois Award for Outstanding Research in SLE, American College of Rheumatology, 1999
Websites
Publications
  1. Performance of the 2019 EULAR/ACR classification criteria for systemic lupus erythematosus in early disease, across sexes and ethnicities.
  2. CALIBRATE: A Phase 2 Randomized Trial of Rituximab Plus Cyclophosphamide Followed by Belimumab for the Treatment of Lupus Nephritis.
  3. Integrated urine proteomics and renal single-cell genomics identify an interferon-? response gradient in lupus nephritis.
  4. A Tale of Two Trials.
  5. The Validity of Scores from the New MCAT Exam in Predicting Student Performance: Results from a Multisite Study.
  6. The Accelerating Medicines Partnership - Organizational Structure and Preliminary Data from the Phase 1 Studies of Lupus Nephritis.
  7. Georgia Abortion Law and our Commitment to Patients.
  8. Design and application of single-cell RNA sequencing to study kidney immune cells in lupus nephritis.
  9. PD-1hi CXCR5- T peripheral helper cells promote B cells responses in lupus via MAF and IL-21.
  10. Publisher Correction: The immune cell landscape in kidneys of patients with lupus nephritis.
  11. 2019 European League Against Rheumatism/American College of Rheumatology Classification Criteria for Systemic Lupus Erythematosus.
  12. Integrated safety profile of atacicept: an analysis of pooled data from the atacicept clinical trial programme.
  13. 2019 European League Against Rheumatism/American College of Rheumatology classification criteria for systemic lupus erythematosus.
  14. The immune cell landscape in kidneys of patients with lupus nephritis.
  15. Do Admissions Multiple Mini-Interview and Traditional Interview Scores Predict Subsequent Academic Performance? A Study of Five California Medical Schools.
  16. Multicriteria decision analysis process to develop new classification criteria for systemic lupus erythematosus.
  17. Adoptive Regulatory T Cell Therapy in a Patient with Systemic Lupus Erythematosus.
  18. Use of Consensus Methodology to Determine Candidate Items for Systemic Lupus Erythematosus Classification Criteria.
  19. Medical School Applicant Characteristics Associated With Performance in Multiple Mini-Interviews Versus Traditional Interviews: A Multi-Institutional Study.
  20. Limited Reliability of the Spot Urine Protein/Creatinine Ratio in the Longitudinal Evaluation of Patients With Lupus Nephritis.
  21. Developing and Refining New Candidate Criteria for Systemic Lupus Erythematosus Classification: An International Collaboration.
  22. Reliability of Multiple Mini-Interviews and traditional interviews within and between institutions: a study of five California medical schools.
  23. Correlation of hypogammaglobulinaemia with proteinuria, and the relationship between hypogammaglobulinaemia and infection in active lupus nephritis.
  24. Post Hoc Analysis of the Phase II/III APRIL-SLE Study: Association Between Response to Atacicept and Serum Biomarkers Including BLyS and APRIL.
  25. In memoriam: Ephraim P. Engleman, MD, 1911-2015.
  26. Identification of clinical and serological factors during induction treatment of lupus nephritis that are associated with renal outcome.
  27. Crossing the Atlantic: the Euro-Lupus Nephritis regimen in North America.
  28. Efficacy and safety of atacicept for prevention of flares in patients with moderate-to-severe systemic lupus erythematosus (SLE): 52-week data (APRIL-SLE randomised trial).
  29. Comparison of alternative primary outcome measures for use in lupus nephritis clinical trials.
  30. Recent progress in conventional and biologic therapy for systemic lupus erythematosus.
  31. Abatacept for lupus nephritis: alternative definitions of complete response support conflicting conclusions.
  32. Mycophenolate versus azathioprine as maintenance therapy for lupus nephritis.
  33. A 24-week, randomized, double-blind, placebo-controlled, parallel group study of the efficacy of oral SCIO-469, a p38 mitogen-activated protein kinase inhibitor, in patients with active rheumatoid arthritis.
  34. Identification of biomarkers that predict response to treatment of lupus nephritis with mycophenolate mofetil or pulse cyclophosphamide.
  35. Plagiarism on personal statements: a disturbing symptom of a broader trend.
  36. Connective tissue diseases: Belimumab for systemic lupus erythematosus: breaking through?
  37. Biologic therapy for systemic lupus erythematosus.
  38. Nonrenal disease activity following mycophenolate mofetil or intravenous cyclophosphamide as induction treatment for lupus nephritis: findings in a multicenter, prospective, randomized, open-label, parallel-group clinical trial.
  39. Influence of race/ethnicity on response to lupus nephritis treatment: the ALMS study.
  40. Regulatory T cells as therapeutic targets in rheumatoid arthritis.
  41. Systemic lupus erythematosus clinical trials-an interim analysis.
  42. Mycophenolate mofetil versus cyclophosphamide for induction treatment of lupus nephritis.
  43. Professional medical associations and their relationships with industry: a proposal for controlling conflict of interest.
  44. A quality indicator set for systemic lupus erythematosus.
  45. 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.
  46. Mycophenolate mofetil as induction and maintenance therapy for lupus nephritis: rationale and protocol for the randomized, controlled Aspreva Lupus Management Study (ALMS).
  47. Clinical trial design in systemic lupus erythematosus.
  48. Inhibition of T cell costimulation: an emerging therapeutic strategy for autoimmune rheumatic diseases.
  49. Living in a different world.
  50. Block and tackle: CTLA4Ig takes on lupus.
  51. Treatment of systemic lupus erythematosus by inhibition of T cell costimulation with anti-CD154: a randomized, double-blind, placebo-controlled trial.
  52. Treatment of autoimmune diseases by inhibition of T-cell costimulation.
  53. The immune tolerance network and rheumatic disease: immune tolerance comes to the clinic.
  54. Cutting edge: reversal of murine lupus nephritis with CTLA4Ig and cyclophosphamide.
  55. Nephritogenic cytokines and disease in MRL-Fas(lpr) kidneys are dependent on multiple T-cell subsets.
  56. Phase I clinical trial of a monoclonal antibody against CD40-ligand (IDEC-131) in patients with systemic lupus erythematosus.
  57. Treatment of autoimmunity by inhibition of T cell costimulation.
  58. The effect on immunoglobulin glycosylation of altering in vivo production of immunoglobulin G.
  59. Effects of anti-B7 monoclonal antibodies on humoral immune responses.
  60. On the horizon: clinical trials of new immunosuppressive strategies for autoimmune diseases.
  61. Opportunities for future biological therapy in SLE.
  62. Enhanced lymphoproliferation and diminished autoimmunity in CD4-deficient MRL/lpr mice.
  63. Long-term inhibition of murine lupus by brief simultaneous blockade of the B7/CD28 and CD40/gp39 costimulation pathways.
  64. The CD28-B7 costimulatory pathway and its role in autoimmune disease.
  65. Blind T-cell homeostasis in CD4-deficient mice.
  66. Treatment of murine lupus with CTLA4Ig.
  67. Interleukin 6 promotes murine lupus in NZB/NZW F1 mice.
  68. Treatment of murine lupus with monoclonal antibodies to lymphocyte function-associated antigen-1: dose-dependent inhibition of autoantibody production and blockade of the immune response to therapy.
  69. Recent advances in the treatment of rheumatic diseases: new approaches to immunotherapy.
  70. T-cell homeostasis: implications in HIV infection .
  71. Treatment of murine lupus with anti-CD4 monoclonal antibodies.
  72. The role of T-cell subsets in the response to anti-CD3 monoclonal antibodies.
  73. Development of murine lupus in CD4-depleted NZB/NZW mice. Sustained inhibition of residual CD4+ T cells is required to suppress autoimmunity.
  74. Tumorigenesis mediated by an antigen receptor.
  75. CD4 antibody therapy in systemic lupus erythematosus.
  76. F(ab')2 anti-CD4 and intact anti-CD4 monoclonal antibodies inhibit the accumulation of CD4+ T cells, CD8+ T cells, and B cells in the kidneys of lupus-prone NZB/NZW mice.
  77. Regulation of immunity by anti-T-cell antibodies.
  78. Effects of recombinant murine tumor necrosis factor-alpha on immune function.
  79. Treatment of murine lupus with monoclonal antibody to L3T4. II. Effects on immunohistopathology of thymus, spleen, and lymph node.
  80. Chronic therapy with recombinant tumor necrosis factor-alpha in autoimmune NZB/NZW F1 mice.
  81. Effects of selective depletion of L3T4+ T-lymphocytes on herpes simplex virus encephalitis.
  82. Treatment of murine lupus with F(ab')2 fragments of monoclonal antibody to L3T4. Suppression of autoimmunity does not depend on T helper cell depletion.
  83. New therapies for the rheumatic diseases.
  84. Treatment of murine lupus with monoclonal antibody to L3T4. I. Effects on the distribution and function of lymphocyte subsets and on the histopathology of autoimmune disease.
  85. The role of Lyt-2+ T cells in the regulation of autoimmunity in murine lupus.
  86. Induction of immune tolerance during administration of monoclonal antibody to L3T4 does not depend on depletion of L3T4+ cells.
  87. Selective manipulation of the immune response in vivo by monoclonal antibodies.
  88. Treatment of autoimmune diseases with monoclonal antibodies.
  89. New approaches to treating systemic lupus erythematosus.
  90. Proliferation of Ly-1 B cells in autoimmune NZB and (NZB x NZW)F1 mice.
  91. Reversal of advanced murine lupus in NZB/NZW F1 mice by treatment with monoclonal antibody to L3T4.
  92. Administration of F(ab')2 fragments of monoclonal antibody to L3T4 inhibits humoral immunity in mice without depleting L3T4+ cells.
  93. Rejection of skin grafts and generation of cytotoxic T cells by mice depleted of L3T4+ cells.
  94. Induction of immune tolerance by administration of monoclonal antibody to L3T4.
  95. Administration of monoclonal anti-T cell antibodies retards murine lupus in BXSB mice.
  96. Anti-Ly-1 antibody induces interleukin 2 release from T cells.
  97. Analysis of the function of L3T4+ T cells by in vivo treatment with monoclonal antibody to L3T4.
  98. Strategies for treating autoimmune disease with monoclonal antibodies.
  99. Antibodies to Tp67 and Tp44 augment and sustain proliferative responses of activated T cells.
  100. Inhibition of humoral immunity in vivo by monoclonal antibody to L3T4: studies with soluble antigens in intact mice.
  101. Successful treatment of autoimmunity in NZB/NZW F1 mice with monoclonal antibody to L3T4.
  102. Treatment of murine lupus with monoclonal anti-T cell antibody.
  103. [Not Available].
  104. Hormones, handedness, and autoimmunity.
  105. The proliferating cells in autoimmune MRL/lpr mice lack L3T4, an antigen on "helper" T cells that is involved in the response to class II major histocompatibility antigens.
  106. Monocytosis in the BXSB model for systemic lupus erythematosus.
  107. Treatment of autoimmune MRL/Ipr mice with monoclonal antibody to Thy-1.2: a single injection has sustained effects on lymphoproliferation and renal disease.
  108. Effects of castration and sex hormones on immune clearance and autoimmune disease in MRL/Mp-lpr/lpr and MRL/Mp-+/+ mice.
  109. Interleukin-2 deficiency, genes, and systemic lupus erythematosus.
  110. Thymic influences on autoimmunity in MRL-lpr mice.
  111. Interleukin 2 deficiency is a common feature of autoimmune mice.
  112. Deficient interleukin 2 activity in MRL/Mp and C57BL/6J mice bearing the lpr gene.
  113. Interleukin-2 deficiency in murine systemic lupus erythematosus.
  114. Culture-negative septic arthritis and bacterial endocarditis. Diagnosis by synovial biopsy.
  115. Coccidioidomycosis of the thyroid.