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Julie Zikherman, MD

Title(s)Associate Professor, Medicine
SchoolSchool of Medicine
Phone415-476-1689
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    Collapse Biography 
    Collapse Education and Training
    Harvard University, Cambridge, MAB.A.1996Chemistry
    Cornell University, New York, NYM.D.2002School of Medicine
    Brigham and Women's Hospital, Boston, MA2005Internal Medicine Residency
    UCSF, San Francisco, CA2008Rheumatology Fellowship

    Collapse Overview 
    Collapse Overview
    Our laboratory is interested in understanding how autoreactive B cells, despite chronic antigen engagement of the B cell receptor, are restrained from inappropriate activation and differentiation. We are interested in how this process is disrupted in autoimmune disease, and how tolerance mechanisms can be harnessed to treat autoimmunity. To do so, we are taking advantage of novel reporter mice in which autoreactive B cells are fluorescently marked (Nur77-eGFP BAC transgenic line). Current funded projects include dissecting the distinct roles of the IgM and IgD B cell receptor isotypes in regulating immune responses by autoreactive B cells. More recent work is focused on defining how Nur77 and related orphan nuclear hormone receptors function selectively to restrain activation of chronically antigen-activated B cells.

    Collapse Research 
    Collapse Research Activities and Funding
    Dissecting unique functions of IgM and IgD BCRs in tolerance and autoimmunity
    NIH/NIAMS R01AR069520Jun 1, 2016 - Mar 31, 2021
    Role: Principal Investigator
    Titrating CD45 expression in mice to study development of T cell tolerance
    NIH/NIAMS K08AR059723Jul 1, 2010 - Jun 30, 2015
    Role: Principal Investigator

    Collapse ORNG Applications 
    Collapse Featured Publications
    Collapse Websites

    Collapse Bibliographic 
    Collapse Publications
    Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Researchers can login to make corrections and additions, or contact us for help.
    List All   |   Timeline
    1. Tan C, Noviski M, Huizar J, Zikherman J. Self-reactivity on a spectrum: A sliding scale of peripheral B cell tolerance. Immunol Rev. 2019 Oct 20. PMID: 31631352.
      View in: PubMed
    2. Rosenthal DG, Parwani P, Murray TO, Petek BJ, Benn BS, De Marco T, Gerstenfeld EP, Janmohamed M, Klein L, Lee BK, Moss JD, Scheinman MM, Hsia HH, Selby V, Koth LL, Pampaloni MH, Zikherman J, Vedantham V. Long-Term Corticosteroid-Sparing Immunosuppression for Cardiac Sarcoidosis. J Am Heart Assoc. 2019 Sep 17; 8(18):e010952. PMID: 31538835.
      View in: PubMed
    3. Ashouri JF, Hsu LY, Yu S, Rychkov D, Chen Y, Cheng DA, Sirota M, Hansen E, Lattanza L, Zikherman J, Weiss A. Reporters of TCR signaling identify arthritogenic T cells in murine and human autoimmune arthritis. Proc Natl Acad Sci U S A. 2019 Sep 10; 116(37):18517-18527. PMID: 31455730.
      View in: PubMed
    4. Noviski M, Tan C, Huizar J, Vykunta V, Mueller JL, Zikherman J. Optimal Development of Mature B Cells Requires Recognition of Endogenous Antigens. J Immunol. 2019 Jul 15; 203(2):418-428. PMID: 31167773.
      View in: PubMed
    5. Zikherman J. GC B cells 'AKT' to blunt BCR signaling. Nat Immunol. 2019 06; 20(6):671-674. PMID: 31011188.
      View in: PubMed
    6. Tan C, Mueller JL, Noviski M, Huizar J, Lau D, Dubinin A, Molofsky A, Wilson PC, Zikherman J. Nur77 Links Chronic Antigen Stimulation to B Cell Tolerance by Restricting the Survival of Self-Reactive B Cells in the Periphery. J Immunol. 2019 May 15; 202(10):2907-2923. PMID: 30962292.
      View in: PubMed
    7. Noviski M, Zikherman J. Control of autoreactive B cells by IgM and IgD B cell receptors: maintaining a fine balance. Curr Opin Immunol. 2018 12; 55:67-74. PMID: 30292928.
      View in: PubMed
    8. Noviski M, Mueller JL, Satterthwaite A, Garrett-Sinha LA, Brombacher F, Zikherman J. IgM and IgD B cell receptors differentially respond to endogenous antigens and control B cell fate. Elife. 2018 03 09; 7. PMID: 29521626.
      View in: PubMed
    9. Huizar J, Tan C, Noviski M, Mueller JL, Zikherman J. Nur77 Is Upregulated in B-1a Cells by Chronic Self-Antigen Stimulation and Limits Generation of Natural IgM Plasma Cells. Immunohorizons. 2017 Nov 01; 1(9):188-197. PMID: 29152611.
      View in: PubMed
    10. Zikherman J, Lowell CA. B cell autoimmunity at the extremes. Nat Immunol. 2017 09 19; 18(10):1065-1066. PMID: 28926534.
      View in: PubMed
    11. Myers DR, Zikherman J, Roose JP. Tonic Signals: Why Do Lymphocytes Bother? Trends Immunol. 2017 11; 38(11):844-857. PMID: 28754596.
      View in: PubMed
    12. Myers DR, Lau T, Markegard E, Lim HW, Kasler H, Zhu M, Barczak A, Huizar JP, Zikherman J, Erle DJ, Zhang W, Verdin E, Roose JP. Tonic LAT-HDAC7 Signals Sustain Nur77 and Irf4 Expression to Tune Naive CD4 T Cells. Cell Rep. 2017 05 23; 19(8):1558-1571. PMID: 28538176.
      View in: PubMed
    13. Au-Yeung BB, Smith GA, Mueller JL, Heyn CS, Jaszczak RG, Weiss A, Zikherman J. IL-2 Modulates the TCR Signaling Threshold for CD8 but Not CD4 T Cell Proliferation on a Single-Cell Level. J Immunol. 2017 03 15; 198(6):2445-2456. PMID: 28159902.
      View in: PubMed
    14. Coughlin S, Noviski M, Mueller JL, Chuwonpad A, Raschke WC, Weiss A, Zikherman J. An extracatalytic function of CD45 in B cells is mediated by CD22. Proc Natl Acad Sci U S A. 2015 Nov 24; 112(47):E6515-24. PMID: 26561584.
      View in: PubMed
    15. 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. PMID: 25769918.
      View in: PubMed
    16. Mueller J, Matloubian M, Zikherman J. Cutting edge: An in vivo reporter reveals active B cell receptor signaling in the germinal center. J Immunol. 2015 Apr 01; 194(7):2993-7. PMID: 25725108.
      View in: PubMed
    17. Zikherman J, Au-Yeung B. The role of T cell receptor signaling thresholds in guiding T cell fate decisions. Curr Opin Immunol. 2015 Apr; 33:43-8. PMID: 25660212.
      View in: PubMed
    18. 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 02; 111(35):E3679-88. PMID: 25136127.
      View in: PubMed
    19. 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. PMID: 24908390.
      View in: PubMed
    20. 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. PMID: 24515435.
      View in: PubMed
    21. Tan YX, Zikherman J, Weiss A. Novel tools to dissect the dynamic regulation of TCR signaling by the kinase Csk and the phosphatase CD45. Cold Spring Harb Symp Quant Biol. 2013; 78:131-139. PMID: 24100586.
      View in: PubMed
    22. Zikherman J, Parameswaran R, Hermiston M, Weiss A. The structural wedge domain of the receptor-like tyrosine phosphatase CD45 enforces B cell tolerance by regulating substrate specificity. J Immunol. 2013 Mar 15; 190(6):2527-35. PMID: 23396948.
      View in: PubMed
    23. Mukherjee S, Zhu J, Zikherman J, Parameswaran R, Kadlecek TA, Wang Q, Au-Yeung B, Ploegh H, Kuriyan J, Das J, Weiss A. Monovalent and multivalent ligation of the B cell receptor exhibit differential dependence upon Syk and Src family kinases. Sci Signal. 2013 Jan 01; 6(256):ra1. PMID: 23281368.
      View in: PubMed
    24. Zikherman J, Parameswaran R, Weiss A. Endogenous antigen tunes the responsiveness of naive B cells but not T cells. Nature. 2012 Sep 06; 489(7414):160-4. PMID: 22902503.
      View in: PubMed
    25. Zikherman J, Doan K, Parameswaran R, Raschke W, Weiss A. Quantitative differences in CD45 expression unmask functions for CD45 in B-cell development, tolerance, and survival. Proc Natl Acad Sci U S A. 2012 Jan 03; 109(1):E3-12. PMID: 22135465.
      View in: PubMed
    26. Zikherman J, Weiss A. Unraveling the functional implications of GWAS: how T cell protein tyrosine phosphatase drives autoimmune disease. J Clin Invest. 2011 Dec; 121(12):4618-21. PMID: 22080861.
      View in: PubMed
    27. Zikherman J, Jenne C, Watson S, Doan K, Raschke W, Goodnow CC, Weiss A. CD45-Csk phosphatase-kinase titration uncouples basal and inducible T cell receptor signaling during thymic development. Immunity. 2010 Mar 26; 32(3):342-54. PMID: 20346773.
      View in: PubMed
    28. Chakraborty AK, Das J, Zikherman J, Yang M, Govern CC, Ho M, Weiss A, Roose J. Molecular origin and functional consequences of digital signaling and hysteresis during Ras activation in lymphocytes. Sci Signal. 2009 Apr 14; 2(66):pt2. PMID: 19366993.
      View in: PubMed
    29. Zikherman J, Hermiston M, Steiner D, Hasegawa K, Chan A, Weiss A. PTPN22 deficiency cooperates with the CD45 E613R allele to break tolerance on a non-autoimmune background. J Immunol. 2009 Apr 01; 182(7):4093-106. PMID: 19299707.
      View in: PubMed
    30. Hermiston ML, Zikherman J, Zhu JW. CD45, CD148, and Lyp/Pep: critical phosphatases regulating Src family kinase signaling networks in immune cells. Immunol Rev. 2009 Mar; 228(1):288-311. PMID: 19290935.
      View in: PubMed
    31. Zikherman J, Weiss A. Antigen receptor signaling in the rheumatic diseases. Arthritis Res Ther. 2009; 11(1):202. PMID: 19232064.
      View in: PubMed
    32. Das J, Ho M, Zikherman J, Govern C, Yang M, Weiss A, Chakraborty AK, Roose JP. Digital signaling and hysteresis characterize ras activation in lymphoid cells. Cell. 2009 Jan 23; 136(2):337-51. PMID: 19167334.
      View in: PubMed
    33. Hermiston ML, Zikherman J, Tan AL, Lam VC, Cresalia NM, Oksenberg N, Goren N, Brassat D, Oksenberg JR, Weiss A. Differential impact of the CD45 juxtamembrane wedge on central and peripheral T cell receptor responses. Proc Natl Acad Sci U S A. 2009 Jan 13; 106(2):546-51. PMID: 19129486.
      View in: PubMed
    34. Zikherman J, Weiss A. Alternative splicing of CD45: the tip of the iceberg. Immunity. 2008 Dec 19; 29(6):839-41. PMID: 19100695.
      View in: PubMed
    35. Prasad A, Zikherman J, Das J, Roose JP, Weiss A, Chakraborty AK. Origin of the sharp boundary that discriminates positive and negative selection of thymocytes. Proc Natl Acad Sci U S A. 2009 Jan 13; 106(2):528-33. PMID: 19098101.
      View in: PubMed