Julie Zikherman, MD
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Title(s) | Associate Professor, Medicine |
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School | School of Medicine |
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Address | 513 Parnassus Ave, HSW San Francisco CA 94143
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Phone | 415-476-1689 |
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ORCID
.gif) | 0000-0002-0873-192X  |
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vCard | Download vCard |
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Biography Harvard University, Cambridge, MA | B.A. | 1996 | Chemistry | Cornell University, New York, NY | M.D. | 2002 | School of Medicine | Brigham and Women's Hospital, Boston, MA | | 2005 | Internal Medicine Residency | UCSF, San Francisco, CA | | 2008 | Rheumatology Fellowship |
Overview Our laboratory is interested in understanding how B cell behavior is regulated after encounter with either “self” or “foreign” antigens. We postulate that overlapping mechanisms are at play in both scenarios. The lab seeks to define the rules that govern B cell responses to specific features of foreign antigens, including antigen affinity, valency and co-stimulatory signals. We are also interested in how the clonal composition of both the pre- and post-immune B cell repertoires is regulated. Against this backdrop, we want to understand how self-reactive B cells, despite chronic antigen engagement of the B cell receptor, are restrained from inappropriate activation and differentiation into antibody-secreting plasma cells. We want to define how this process is disrupted in a variety of autoimmune disease states, and how normal regulatory mechanisms (both biochemical and transcriptional) can be harnessed to restore tolerance and optimize vaccine responses.
To do so, our lab takes a range of creative approaches that span mouse genetics, cellular immunology, and genomics in order to address these questions. In particular, we have characterized and exploited novel reporter mice (NUR77-eGFP BAC transgenic) in which B cell receptor signaling drives expression of eGFP. This reporter serves as an in vivo sensor of both self and foreign antigen encounter, and serves to unmask enormous clonal heterogeneity among superficially uniform populations of B cells. Recent work has focused on dissecting the distinct roles of the IgM and IgD B cell receptor isotypes in regulating the immune responses of self-reactive B cells. Newer projects seek to define how NUR77 and related orphan nuclear hormone receptors of the NR4A family function to restrain activation of chronically antigen-activated B cells and to regulate B responses to foreign antigen.
Research ORNG Applications Bibliographic
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The BAFFling persistence of memory B cells. J Exp Med. 2021 Feb 01; 218(2).
Brooks JF, Zikherman J. PMID: 33185684.
View in: PubMed Mentions: Fields:
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NR4A nuclear receptors restrain B cell responses to antigen when second signals are absent or limiting. Nat Immunol. 2020 10; 21(10):1267-1279.
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: 1 Fields:
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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: 3 Fields:
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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
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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
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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: 3 Fields: Translation: HumansAnimalsCells
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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: 4 Fields: Translation: AnimalsCells
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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
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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: 5 Fields: Translation: AnimalsCells
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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: Fields: Translation: HumansAnimalsCells
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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: 10 Fields: Translation: AnimalsCells
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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: 5 Fields:
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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
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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: 14 Fields: Translation: HumansAnimalsCells
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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: 7 Fields: Translation: HumansAnimalsCells
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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: 17 Fields: Translation: AnimalsCells
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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
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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
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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: 19 Fields: Translation: AnimalsCells
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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: 15 Fields: Translation: HumansAnimalsCells
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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: 45 Fields: Translation: AnimalsCells
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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: 22 Fields: Translation: AnimalsCells
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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
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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
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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
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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: 29 Fields: Translation: HumansAnimalsCells
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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: 121 Fields: Translation: AnimalsCells
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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: 19 Fields: Translation: AnimalsCells
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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
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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
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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
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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: 71 Fields: Translation: HumansAnimalsCells
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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
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Antigen receptor signaling in the rheumatic diseases. Arthritis Res Ther. 2009; 11(1):202.
Zikherman J, Weiss A. PMID: 19232064.
View in: PubMed Mentions: 14 Fields: Translation: HumansAnimalsCells
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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: 171 Fields: Translation: HumansAnimalsCells
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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
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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
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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: 19 Fields: Translation: HumansAnimalsCells
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Year | Publications |
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2008 | 2 | 2009 | 6 | 2010 | 1 | 2011 | 2 | 2012 | 1 | 2013 | 3 | 2014 | 3 | 2015 | 4 | 2017 | 5 | 2018 | 2 | 2019 | 6 | 2020 | 2 | 2021 | 1 |
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Note that an individual publication can be assigned to more than one field. As a result, the publication counts in this graph might add up to more than the number of publications the person has written.
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