Arthur Weiss, MD, PhD

Arthur Weiss, MD, PhD

Professor, Departments of Medicine, Microbiology and Immunology; Investigator, Howard Hughes Medical Institute, UCSF
Ephraim P. Engleman Distinguished Professorship, UCSF

Phone: (415) 476-8983 (voice)
Box 0795, UCSF
San Francisco, CA 94143-0795

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Research Summary

I have studied signal transduction in lymphocytes for more than 30 years, with a recent focused interest in the role of cytoplasmic tyrosine kinases and transmembrane phosphatases, molecules critically important in normal lymphocyte responses to pathogens and in responses to tumors. Mutations of some of these molecules within the hematopoietic lineage can lead to malignant transformation. I have studied the influence of dysregulation of tyrosine kinases, particularly of ZAP-70, and phosphatases such as CD45 and CD148 in mouse models of lymphoproliferation, a frequent precursor of malignant transformation. My lab discovered ZAP-70, demonstrated its importance in T cell antigen receptor signaling, and was one of the first to report ZAP-70 mutations as a cause of human SCID. We have also collaborated with Tom Kipps (UCSD) on the expression of ZAP-70 in human Chronic Lymphocytic Leukemia (CLL) as a prognostic marker and have studied its role in CLL cells. We have established several mouse models of ZAP-70, Csk, and CD45 mutant alleles to understand the consequences of these alleles on lymphocyte signaling.

During my career, I have served on the Scientific Advisory Boards of several biotechnology companies. Two have successful FDA-approved therapies for malignancies. Sunitinib, whose early development occurred at Sugen and then at Pfizer, has been approved for renal cell carcinoma, gastrointestinal stromal tumors, and neuroendocrine pancreatic tumors. Plexxikon developed Vemurafinib, a pioneering targeted therapeutic for melanomas harboring the BRAF V600E mutation, which occurs in approximately half of melanoma patients. I am a cofounder of Nurix, Inc., which seeks to develop therapeutics for various malignancies by targeting ubiquitin ligases.


University of Chicago, Chicago, IL, Ph.D., 1978, Immunology
University of Chicago, Chicago, IL, M.D., 1979, Medicine

Professional Experience

  • 1979-1980
    Postdoctoral Fellow, Swiss Institute for Experimental Cancer Research, Lausanne, Switzerland
  • 1980-1982
    Resident, Department of Medicine, University of California, San Francisco (UCSF)
  • 1982-1984
    Fellow in Rheumatology/Clinical Immunology, UCSF
  • 1982-1985
    Associate, Howard Hughes Medical Institute, UCSF
  • 1984-1985
    Instructor, Department of Medicine, Division of Rheumatology/Clinical Immunology, UCSF
  • 1985-1989
    Assistant Investigator, Howard Hughes Medical Institute, UCSF
  • 1985-1989
    Assistant Professor of Medicine, Microbiology and Immunology, UCSF
  • 1987-2011
    Chief, Division of Rheumatology/Clinical Immunology, Department of Medicine, UCSF
  • 1989-1993
    Associate Professor or Medicine, Microbiology and Immunology, UCSF
  • 1989-1994
    Associate Investigator, Howard Hughes Medical Institute, UCSF
  • 1991-present
    Ephraim P. Engleman Distinguished Professor of Rheumatology, UCSF
  • 1992-present
    Professor of Medicine, Microbiology and Immunology, UCSF
  • 1993-present
    Investigator, Howard Hughes Medical Institute, UCSF
  • 1998-2005
    Associate Director, The Rosalind Russell Medical Research Center for Arthritis, UCSF
  • 2002-2006
    Director, Medical Scientist Training Program (MSTP), UCSF
  • 2007-2010
    Co-Director, Institute for Molecular Medicine, UCSF

Honors & Awards

  • 1997
    Lee C. Howley Prize, Arthritis Foundation
  • 1998
    Forty-First Faculty Research Lecturer, UCSF
  • 2001
    American Association of Immunologist-Huang Foundation Meritorious Career Award
  • 2003
    Fellow, American Academy of Arts and Sciences
  • 2004
    Member, National Academy of Sciences
  • 2004
    Fellow, American Academy of Microbiology
  • 2004
    Member, Institute of Medicine
  • 2004
    Distinguished Investigator Award, American College of Rheumatology
  • 2012
    Lifetime Achievement Award, American Association of Immunology
  • 2012
    UCSF Lifetime Achievement in Mentoring Award

Selected Publications

  1. Freedman TS, Tan YX, Skrzypczynska KM, Manz BN, Sjaastad FV, Goodridge HS, Lowell CA, Weiss A. LynA regulates an inflammation-sensitive signaling checkpoint in macrophages. Elife. 2015; 4.
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  2. Manz BN, Tan YX, Courtney AH, Rutaganira F, Palmer E, Shokat KM, Weiss A. Small molecule inhibition of Csk alters affinity recognition by T cells. Elife. 2015; 4.
    View on PubMed
  3. Sjölin-Goodfellow H, Frushicheva MP, Ji Q, Cheng DA, Kadlecek TA, Cantor AJ, Kuriyan J, Chakraborty AK, Salomon AR, Weiss A. The catalytic activity of the kinase ZAP-70 mediates basal signaling and negative feedback of the T cell receptor pathway. Sci Signal. 2015; 8(377):ra49.
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  4. Weiss A, Stobo JD. Commentary: "The Role of T3 Surface Molecules in the Activation of Human Cells: A Two-Stimulus Requirement for IL-2 Production Reflects Events Occurring at a Pretranslational Level". Front Immunol. 2015; 6:163.
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  5. Chen Z, Shojaee S, Buchner M, Geng H, Lee JW, Klemm L, Titz B, Graeber TG, Park E, Tan YX, Satterthwaite A, Paietta E, Hunger SP, Willman CL, Melnick A, Loh ML, Jung JU, Coligan JE, Bolland S, Mak TW, Limnander A, Jumaa H, Reth M, Weiss A, Lowell CA, Müschen M. Signalling thresholds and negative B-cell selection in acute lymphoblastic leukaemia. Nature. 2015 May 21; 521(7552):357-61.
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  6. Tian R, Wang H, Gish GD, Petsalaki E, Pasculescu A, Shi Y, Mollenauer M, Bagshaw RD, Yosef N, Hunter T, Gingras AC, Weiss A, Pawson T. Combinatorial proteomic analysis of intercellular signaling applied to the CD28 T-cell costimulatory receptor. Proc Natl Acad Sci U S A. 2015 Mar 31; 112(13):E1594-603.
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  7. Mills RE, Lam VC, Tan A, Cresalia N, Oksenberg N, Zikherman J, Anderson M, Weiss A, Hermiston ML. Unbiased Modifier Screen Reveals That Signal Strength Determines the Regulatory Role Murine TLR9 Plays in Autoantibody Production. J Immunol. 2015 Apr 15; 194(8):3675-86.
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  8. Punwani D, Wang H, Chan AY, Cowan MJ, Mallott J, Sunderam U, Mollenauer M, Srinivasan R, Brenner SE, Mulder A, Claas FH, Weiss A, Puck JM. Combined Immunodeficiency Due to MALT1 Mutations, Treated by Hematopoietic Cell Transplantation. J Clin Immunol. 2015 Feb; 35(2):135-46.
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  9. Visperas PR, Winger JA, Horton TM, Shah NH, Aum DJ, Tao A, Barros T, Yan Q, Wilson CG, Arkin MR, Weiss A, Kuriyan J. Modification by covalent reaction or oxidation of cysteine residues in the tandem-SH2 domains of ZAP-70 and Syk can block phosphopeptide binding. Biochem J. 2015 Jan 1; 465(1):149-61.
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  10. Chakraborty AK, Weiss A. Insights into the initiation of TCR signaling. Nat Immunol. 2014 Sep; 15(9):798-807.
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  11. Au-Yeung BB, Zikherman J, Mueller JL, Ashouri JF, Matloubian M, Cheng DA, Chen Y, Shokat KM, Weiss A. A sharp T-cell antigen receptor signaling threshold for T-cell proliferation. Proc Natl Acad Sci U S A. 2014 Sep 2; 111(35):E3679-88.
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  12. Schim van der Loeff I, Hsu LY, Saini M, Weiss A, Seddon B. Zap70 is essential for long-term survival of naive CD8 T cells. J Immunol. 2014 Sep 15; 193(6):2873-80.
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  13. Ross JO, Melichar HJ, Au-Yeung BB, Herzmark P, Weiss A, Robey EA. Distinct phases in the positive selection of CD8+ T cells distinguished by intrathymic migration and T-cell receptor signaling patterns. Proc Natl Acad Sci U S A. 2014 Jun 24; 111(25):E2550-8.
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  14. Au-Yeung BB, Melichar HJ, Ross JO, Cheng DA, Zikherman J, Shokat KM, Robey EA, Weiss A. Quantitative and temporal requirements revealed for Zap70 catalytic activity during T cell development. Nat Immunol. 2014 Jul; 15(7):687-94.
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  15. Phee H, Au-Yeung BB, Pryshchep O, O'Hagan KL, Fairbairn SG, Radu M, Kosoff R, Mollenauer M, Cheng D, Chernoff J, Weiss A. Pak2 is required for actin cytoskeleton remodeling, TCR signaling, and normal thymocyte development and maturation. Elife. 2014; 3:e02270.
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  16. Wang H, Flach H, Onizawa M, Wei L, McManus MT, Weiss A. Negative regulation of Hif1a expression and TH17 differentiation by the hypoxia-regulated microRNA miR-210. Nat Immunol. 2014 Apr; 15(4):393-401.
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  17. Jenkins MR, Stinchcombe JC, Au-Yeung BB, Asano Y, Ritter AT, Weiss A, Griffiths GM. Distinct structural and catalytic roles for Zap70 in formation of the immunological synapse in CTL. Elife. 2014; 3:e01310.
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  18. Limnander A, Zikherman J, Lau T, Leitges M, Weiss A, Roose JP. Protein kinase Cd promotes transitional B cell-negative selection and limits proximal B cell receptor signaling to enforce tolerance. Mol Cell Biol. 2014 Apr; 34(8):1474-85.
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  19. Tan YX, Manz BN, Freedman TS, Zhang C, Shokat KM, Weiss A. Inhibition of the kinase Csk in thymocytes reveals a requirement for actin remodeling in the initiation of full TCR signaling. Nat Immunol. 2014 Feb; 15(2):186-94.
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  20. Weiss A. Tony Pawson: Modular protein domains and the links to intracellular signaling. Proc Natl Acad Sci U S A. 2013 Oct 29; 110(44):17604-5.
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