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Julie Zikherman, MD

Title(s)Associate Professor, Medicine
SchoolSchool of Medicine
Address513 Parnassus Ave, HSW
San Francisco CA 94143
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

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    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
    Nuclear Receptors in B Cell Tolerance and Humoral Immune Responses
    NIH/NIAID R01AI148487Jun 15, 2020 - May 31, 2025
    Role: Principal Investigator
    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

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    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. to make corrections and additions.
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    Altmetrics Details PMC Citations indicate the number of times the publication was cited by articles in PubMed Central, and the Altmetric score represents citations in news articles and social media. (Note that publications are often cited in additional ways that are not shown here.) Fields are based on how the National Library of Medicine (NLM) classifies the publication's journal and might not represent the specific topic of the publication. Translation tags are based on the publication type and the MeSH terms NLM assigns to the publication. Some publications (especially newer ones and publications not in PubMed) might not yet be assigned Field or Translation tags.) Click a Field or Translation tag to filter the publications.
    1. NR4A nuclear receptors restrain B cell responses to antigen when second signals are absent or limiting. Nat Immunol. 2020 Aug 31. Tan C, Hiwa R, Mueller JL, Vykunta V, Hibiya K, Noviski M, Huizar J, Brooks JF, Garcia J, Heyn C, Li Z, Marson A, Zikherman J. PMID: 32868928.
      View in: PubMed   Mentions:    Fields:    
    2. Synthetic Liposomal Mimics of Biological Viruses for the Study of Immune Responses to Infection and Vaccination. Bioconjug Chem. 2020 03 18; 31(3):685-697. Wholey WY, Mueller JL, Tan C, Brooks JF, Zikherman J, Cheng W. PMID: 31940172.
      View in: PubMed   Mentions: 2     Fields:    
    3. Self-reactivity on a spectrum: A sliding scale of peripheral B cell tolerance. Immunol Rev. 2019 11; 292(1):37-60. Tan C, Noviski M, Huizar J, Zikherman J. PMID: 31631352.
      View in: PubMed   Mentions: 1     Fields:    Translation:HumansAnimalsCells
    4. Long-Term Corticosteroid-Sparing Immunosuppression for Cardiac Sarcoidosis. J Am Heart Assoc. 2019 09 17; 8(18):e010952. 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. PMID: 31538835.
      View in: PubMed   Mentions: 1     Fields:    Translation:Humans
    5. Reporters of TCR signaling identify arthritogenic T cells in murine and human autoimmune arthritis. Proc Natl Acad Sci U S A. 2019 09 10; 116(37):18517-18527. Ashouri JF, Hsu LY, Yu S, Rychkov D, Chen Y, Cheng DA, Sirota M, Hansen E, Lattanza L, Zikherman J, Weiss A. PMID: 31455730.
      View in: PubMed   Mentions: 1     Fields:    Translation:HumansAnimalsCells
    6. Optimal Development of Mature B Cells Requires Recognition of Endogenous Antigens. J Immunol. 2019 07 15; 203(2):418-428. Noviski M, Tan C, Huizar J, Vykunta V, Mueller JL, Zikherman J. PMID: 31167773.
      View in: PubMed   Mentions: 2     Fields:    Translation:AnimalsCells
    7. GC B cells 'AKT' to blunt BCR signaling. Nat Immunol. 2019 06; 20(6):671-674. Zikherman J. PMID: 31011188.
      View in: PubMed   Mentions:    Fields:    Translation:Cells
    8. Nur77 Links Chronic Antigen Stimulation to B Cell Tolerance by Restricting the Survival of Self-Reactive B Cells in the Periphery. J Immunol. 2019 05 15; 202(10):2907-2923. Tan C, Mueller JL, Noviski M, Huizar J, Lau D, Dubinin A, Molofsky A, Wilson PC, Zikherman J. PMID: 30962292.
      View in: PubMed   Mentions: 2     Fields:    Translation:AnimalsCells
    9. Control of autoreactive B cells by IgM and IgD B cell receptors: maintaining a fine balance. Curr Opin Immunol. 2018 12; 55:67-74. Noviski M, Zikherman J. PMID: 30292928.
      View in: PubMed   Mentions: 1     Fields:    Translation:HumansAnimalsCells
    10. IgM and IgD B cell receptors differentially respond to endogenous antigens and control B cell fate. Elife. 2018 03 09; 7. Noviski M, Mueller JL, Satterthwaite A, Garrett-Sinha LA, Brombacher F, Zikherman J. PMID: 29521626.
      View in: PubMed   Mentions: 8     Fields:    Translation:AnimalsCells
    11. 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. Huizar J, Tan C, Noviski M, Mueller JL, Zikherman J. PMID: 29152611.
      View in: PubMed   Mentions: 3     Fields:    
    12. B cell autoimmunity at the extremes. Nat Immunol. 2017 09 19; 18(10):1065-1066. Zikherman J, Lowell CA. PMID: 28926534.
      View in: PubMed   Mentions: 1     Fields:    Translation:Cells
    13. Tonic Signals: Why Do Lymphocytes Bother? Trends Immunol. 2017 11; 38(11):844-857. Myers DR, Zikherman J, Roose JP. PMID: 28754596.
      View in: PubMed   Mentions: 9     Fields:    Translation:HumansAnimalsCells
    14. Tonic LAT-HDAC7 Signals Sustain Nur77 and Irf4 Expression to Tune Naive CD4 T Cells. Cell Rep. 2017 05 23; 19(8):1558-1571. 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. PMID: 28538176.
      View in: PubMed   Mentions: 5     Fields:    Translation:HumansAnimalsCells
    15. 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. Au-Yeung BB, Smith GA, Mueller JL, Heyn CS, Jaszczak RG, Weiss A, Zikherman J. PMID: 28159902.
      View in: PubMed   Mentions: 14     Fields:    Translation:AnimalsCells
    16. 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. Coughlin S, Noviski M, Mueller JL, Chuwonpad A, Raschke WC, Weiss A, Zikherman J. PMID: 26561584.
      View in: PubMed   Mentions: 5     Fields:    Translation:AnimalsCells
    17. 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. Mills RE, Lam VC, Tan A, Cresalia N, Oksenberg N, Zikherman J, Anderson M, Weiss A, Hermiston ML. PMID: 25769918.
      View in: PubMed   Mentions: 6     Fields:    Translation:AnimalsCells
    18. 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. Mueller J, Matloubian M, Zikherman J. PMID: 25725108.
      View in: PubMed   Mentions: 17     Fields:    Translation:AnimalsCells
    19. The role of T cell receptor signaling thresholds in guiding T cell fate decisions. Curr Opin Immunol. 2015 Apr; 33:43-8. Zikherman J, Au-Yeung B. PMID: 25660212.
      View in: PubMed   Mentions: 14     Fields:    Translation:HumansAnimalsCells
    20. 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. Au-Yeung BB, Zikherman J, Mueller JL, Ashouri JF, Matloubian M, Cheng DA, Chen Y, Shokat KM, Weiss A. PMID: 25136127.
      View in: PubMed   Mentions: 40     Fields:    Translation:AnimalsCells
    21. Quantitative and temporal requirements revealed for Zap70 catalytic activity during T cell development. Nat Immunol. 2014 Jul; 15(7):687-94. Au-Yeung BB, Melichar HJ, Ross JO, Cheng DA, Zikherman J, Shokat KM, Robey EA, Weiss A. PMID: 24908390.
      View in: PubMed   Mentions: 19     Fields:    Translation:AnimalsCells
    22. 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. Limnander A, Zikherman J, Lau T, Leitges M, Weiss A, Roose JP. PMID: 24515435.
      View in: PubMed   Mentions: 6     Fields:    Translation:AnimalsCells
    23. 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. Tan YX, Zikherman J, Weiss A. PMID: 24100586.
      View in: PubMed   Mentions: 5     Fields:    Translation:HumansAnimalsCells
    24. 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. Zikherman J, Parameswaran R, Hermiston M, Weiss A. PMID: 23396948.
      View in: PubMed   Mentions: 4     Fields:    Translation:AnimalsCells
    25. 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. Mukherjee S, Zhu J, Zikherman J, Parameswaran R, Kadlecek TA, Wang Q, Au-Yeung B, Ploegh H, Kuriyan J, Das J, Weiss A. PMID: 23281368.
      View in: PubMed   Mentions: 28     Fields:    Translation:HumansAnimalsCells
    26. Endogenous antigen tunes the responsiveness of naive B cells but not T cells. Nature. 2012 Sep 06; 489(7414):160-4. Zikherman J, Parameswaran R, Weiss A. PMID: 22902503.
      View in: PubMed   Mentions: 112     Fields:    Translation:AnimalsCells
    27. 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. Zikherman J, Doan K, Parameswaran R, Raschke W, Weiss A. PMID: 22135465.
      View in: PubMed   Mentions: 18     Fields:    Translation:AnimalsCells
    28. Unraveling the functional implications of GWAS: how T cell protein tyrosine phosphatase drives autoimmune disease. J Clin Invest. 2011 Dec; 121(12):4618-21. Zikherman J, Weiss A. PMID: 22080861.
      View in: PubMed   Mentions: 10     Fields:    Translation:AnimalsCells
    29. CD45-Csk phosphatase-kinase titration uncouples basal and inducible T cell receptor signaling during thymic development. Immunity. 2010 Mar 26; 32(3):342-54. Zikherman J, Jenne C, Watson S, Doan K, Raschke W, Goodnow CC, Weiss A. PMID: 20346773.
      View in: PubMed   Mentions: 52     Fields:    Translation:AnimalsCells
    30. Molecular origin and functional consequences of digital signaling and hysteresis during Ras activation in lymphocytes. Sci Signal. 2009 Apr 14; 2(66):pt2. Chakraborty AK, Das J, Zikherman J, Yang M, Govern CC, Ho M, Weiss A, Roose J. PMID: 19366993.
      View in: PubMed   Mentions: 12     Fields:    Translation:HumansAnimalsCells
    31. 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. Zikherman J, Hermiston M, Steiner D, Hasegawa K, Chan A, Weiss A. PMID: 19299707.
      View in: PubMed   Mentions: 69     Fields:    Translation:HumansAnimalsCells
    32. CD45, CD148, and Lyp/Pep: critical phosphatases regulating Src family kinase signaling networks in immune cells. Immunol Rev. 2009 Mar; 228(1):288-311. Hermiston ML, Zikherman J, Zhu JW. PMID: 19290935.
      View in: PubMed   Mentions: 66     Fields:    Translation:HumansAnimalsCells
    33. Antigen receptor signaling in the rheumatic diseases. Arthritis Res Ther. 2009; 11(1):202. Zikherman J, Weiss A. PMID: 19232064.
      View in: PubMed   Mentions: 13     Fields:    Translation:HumansAnimalsCells
    34. Digital signaling and hysteresis characterize ras activation in lymphoid cells. Cell. 2009 Jan 23; 136(2):337-51. Das J, Ho M, Zikherman J, Govern C, Yang M, Weiss A, Chakraborty AK, Roose JP. PMID: 19167334.
      View in: PubMed   Mentions: 169     Fields:    Translation:HumansAnimalsCells
    35. 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. Hermiston ML, Zikherman J, Tan AL, Lam VC, Cresalia NM, Oksenberg N, Goren N, Brassat D, Oksenberg JR, Weiss A. PMID: 19129486.
      View in: PubMed   Mentions: 6     Fields:    Translation:AnimalsCells
    36. 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. Prasad A, Zikherman J, Das J, Roose JP, Weiss A, Chakraborty AK. PMID: 19098101.
      View in: PubMed   Mentions: 35     Fields:    Translation:AnimalsCells
    37. Alternative splicing of CD45: the tip of the iceberg. Immunity. 2008 Dec 19; 29(6):839-41. Zikherman J, Weiss A. PMID: 19100695.
      View in: PubMed   Mentions: 17     Fields:    Translation:HumansAnimalsCells
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