University of California, San Francisco
513 Parnassus Avenue, Medical Science Bldg., Rm 1032
Box 0795
San Francisco, CA. 94143-0795
phone: 415-502-2279
fax: 415-502-5081
Education
Dr. Zikherman received her M.D. from Cornell Medical College in 2002 and completed internal medicine residency at Brigham and Women’s Hospital in Boston, Massachusetts (2005). She received her fellowship training in Rheumatology at Brigham and Women’s Hospital and at the University of California, San Francisco (2008).
Licensure and Certification
Board certification, Rheumatology (2008)
Board certification, Internal Medicine (2005)
Medical License, State of California
Research Interests
Human autoimmune diseases such as rheumatoid arthritis have a complex genetic basis which is being unraveled through whole genome association studies. Recent progress in the identification of novel human autoimmune susceptibility loci has far surpassed the understanding of the functional consequences of these polymorphisms. Many of these polymorphisms map to molecules which regulate signaling by T and B lymphocytes. Dr. Zikherman is interested in elucidating the functional consequences of such human polymorphisms in order to identify mechanisms of autoimmune disease pathogenesis.
One focus of current research is the gene PTPN22 which encodes a hematopoietic tyrosine phosphatase which negatively regulates T cell receptor (TCR) signaling. A single polymorphism in the coding region of PTPN22 (R620W) confers susceptibility to multiple human autoimmune diseases including RA and systemic lupus erythematosus (SLE). Both in vitro and in vivo studies of the PTPN22 risk allele in cell lines and disease models are underway to identify the effect of the human polymorphism on signaling, development, and immune tolerance.
Peer-reviewed publications
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.
Ashok Prasad, Julie Zikherman, Jayajit Das, Jeroen Roose, Arthur Weiss, and Arup K. Chakraborty. “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.
Jayajit Das, Mary Ho, Julie Zikherman, Arthur Weiss, Arup K. Chakraborty, and Jeroen P. Roose. “Digital signaling and hysteresis characterize Ras activation in lymphoid cells”. Cell. 2009 Jan 23;136(2):337-51.
Julie Zikherman, Michelle Hermiston, Kiminori Hasegawa, Andrew Chan, and Art Weiss. “PTPN22 deficiency cooperates with the CD45 E613R allele to break tolerance on a non-autoimmune background”. J Immunol. 2009 Apr 1;182(7):4093-106.
Julie Zikherman, Susan Watson, Craig Jenne, Kristin Doan, William C. Raschke, Christopher Goodnow, and Arthur Weiss. “CD45-Csk phosphatase-kinase titration uncouples basal and inducible T cell receptor signaling during thymic development.” Immunity. 2010 Mar 26;32(3):342-54.
Reviews and Commentary
Zikherman J, Weiss A. “Alternative splicing of CD45: the tip of the iceberg.” Immunity. 2008 Dec;29(6):839-41.
Zikherman J, Weiss A. “Antigen receptor signaling in the rheumatic diseases.” Arthritis Res Ther. 2009 Jan 30;11(1):202.
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.
Recent Abstracts
Julie Zikherman, Susan Watson, Craig Jenne, William C. Raschke, Christopher Goodnow, Arthur Weiss. “An allelic series of CD45 dosages uncouples basal and inducible TCR signaling during thymic development”. American Association of Immunologists (AAI) National Meeting, Seattle, May 2009 [Platform presentation]
Julie Zikherman, Kristin Doan, Craig Jenne, Susan Watson, Christopher Goodnow, William C. Raschke, and Arthur Weiss. “Titration of CD45 expression Reveals Differential Regulation of Antigen Receptor Signaling in T and B cells and Defines a BCR Signaling Threshold for B Cell Negative Selection”. American College of Rheumatology (ACR) National Meeting, Philadelphia, October 2009 [Poster]
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