Thomas Jefferson University - Kerry S. Campbell
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Kerry S. Campbell
Microbiology and Immunology
Fox Chase Cancer Center
Member, Immune Cell Development and Host Defense Program
Institute for Cancer Research
Appointed: 1998
Thomas Jefferson University
Jefferson Medical College
Jefferson College of Graduate Studies
Department of Microbiology and Immunology
Adjunct Associate Professor
Appointed: 2006
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Mailing Address
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333 Cottman Avenue
Philadelphia, Pennsylvania 19111-2497
United States
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Qualifications
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B.S., Pharmacy, University of Toledo, Toledo, OH, 1983
Ph.D., Pharmacology and Toxicology, Virginia Commonwealth University, Richmond, VA, 1988
Postdoctoral Fellow, National Jewish Center, Denver, CO, 1988-1992
Independent Member, Basel Institute for Immunology, Basel, Switzerland, 1992-1998
Associate Member, Fox Chase Cancer Center, Philadelphia, PA, 1998-2004
Member, Fox Chase Cancer Center, Philadelphia, PA, 2004-present
Adjunct Associate Professor, Department of Microbiology and Immunology, Thomas Jefferson Medical College/College of Graduate Studies, 2006-present
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Expertise and Research Interests
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Signal Transduction in Natural Killer Cells
Natural Killer (NK) cells constitute 10-15% of peripheral blood lymphocytes, and provide an important sentinel component of innate immune responses by killing certain tumor cells and virally infected cells. Improved understanding of human NK cell-mediated cytotoxicity has recently evolved from the discovery of one of their key controlling elements, Killer Cell Inhibitory Receptors (KIR). KIR bind major histocompatibility complex (MHC) class I molecules on adjacent cells, and MHC class I binding suppresses NK cell killing through the transmission of dominant "negative signaling" through KIR. MHC class I molecules are normally expressed on virtually every cell of the body. The loss of MHC class I by some tumor cells and virally infected cells unleashes their killing due to elimination of the KIR negative signals.
Alternatively, a distinctive member of the KIR family of receptors, named KIR2DL4, is highly conserved in primates, including humans. This is an activating receptor that stimulates NK cells to secrete cytokines, but uniquely does not stimulate cytotoxicity responses. KIR2DL4 is only expressed on a small subset of activated NK cells in certain humans, while some individuals cannot express this receptor at all, due to a common genetic polymorphism. Therefore, NK cell responsiveness may be compromised in the many individuals that cannot express this receptor. Some evidence indicates that KIR2DL4 plays a role in pregnancy, but it may also be important in NK cell responses toward tumors or virus-infected cells.
My laboratory studies the molecular mechanisms by which inhibitory KIR and KIR2DL4 regulate NK cell responses. The main focus of the lab is to dissect the signal transduction crosstalk between these activating and inhibitory receptors to define how they control NK cell responses toward tumors and virus-infected cells.
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Keywords
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NK Cells, signal transduction, KIR
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Publications
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- Recent Publications:
- Yusa, S., Catina, T.L., and Campbell, K.S. SHP-1- and phosphotyrosine-independent inhibitory signaling by a killer cell Ig-like receptor cytoplasmic domain in human NK cells. J. Immunol., 168:5047-5057. 2002.
- Yusa, S., and Campbell, K.S. Src homology region 2-containing protein tyrosine phosphatase-2 (SHP-2) can play a direct role in the inhibitory function of killer cell Ig-like receptors in human NK cells. J. Immunol., 170:4539-4547. 2003.
- Kikuchi-Maki, A., Yusa, S., Catina, T.L., and Campbell, K.S. KIR2DL4 is an IL-2 regulated NK cell receptor that exhibits limited expression in humans but triggers strong IFN-gamma production. J. Immunol., 171:3415-3425. 2003.
- Campbell, K.S., Yusa, S., Kikuchi-Maki, A., and Catina, T.L. NKp44 triggers NK cell activation through DAP12 association that is not influenced by a putative cytoplasmic inhibitory sequence. J. Immunol., 172:899-906. 2004.
- Yusa, S., Catina, T.L., and Campbell, K.S. KIR2DL5 can inhibit human NK cell activation via recruitment of Src homology region 2-containing protein tyrosine phosphatase-2 (SHP-2). J. Immunol., 172:7385-7392. 2004.
- Kikuchi-Maki, A., Catina, T.L., and Campbell, K.S. Cutting Edge: KIR2DL4 transduces signals into human NK cells through association with Fc receptor-gamma protein. J. Immunol., 174:3859-3863. 2005.
- MacFarlane IV, A.W., and Campbell, K.S. Signal transduction in natural killer cells. In Curr. Topics Microbiol. Immunol.: Immunobiology of natural killer cell receptors, Vivier, E. and Colonna, M., Eds., Springer, Heidelberg, Germany, 298:23-57. 2006.
- Chen, Y., Perussia, B., and Campbell, K.S. Prostaglandin D2 suppresses human NK cell function via signaling through D prostanoid receptor. J. Immunol., 179:2766-2773. 2007.
- Alvarez-Arias, D.A., and Campbell, K.S. Protein kinase C regulates expression and function of inhibitory killer cell Ig-like receptors in NK cells. J. Immunol. 179: 5281-5290. 2007
- Miah, S.S.M., Hughes, T.L., and Campbell, K.S. KIR2DL4 differentially signals downstream functions in human NK cells through distinct structural modules. J. Immunol. 180: 2922-2932. 2008.
- MacFarlane IV, A.W., Yamazaki, T., Fang, M., Sigal, L.J., Kurosaki, T., and Campbell, K.S. Enhanced NK cell development and function in BCAP-deficient mice. Blood 112:131-140. 2008.
- Binyamin, L., Alpaugh, R.K., Hughes, T.L., Lutz, C.T., Campbell, K.S., and Weiner, L.M. Blocking NK cell inhibitory self-recognition promotes antibody-dependent cellular cytotoxicity in a model of anti-lymphoma therapy. J. Immunol. 180:6392-6401. 2008.
- Purdy, A.K. and Campbell, K.S. SHP-2 expression negatively regulates NK cell function. J. Immunol., In press.
- Borghaei, H., Smith, M.R., and Campbell, K.S. Immunotherapy of Cancer. Eur. J. Pharmacol., in press
- Campbell, K. S., Editor, Natural Killer Cell Protocols: Cellular and Molecular Methods, Second Edition, Methods in Molecular Biology Series, Humana Press/Springer Science, New York, NY, In press.
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Individual Expertise profile of
Kerry S. Campbell, Copyright © Kerry S. Campbell.
Last Updated
by Kerry Campbell : Tuesday, October 13, 2009 6:19:23 PM
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