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Kerry S. Campbell, PhD

Kerry S. Campbell, PhD
About

Associate Professor

Director, Cell Culture Facility​

Research Program

Microtubule organizing center and cytolytic granules orient toward a tumor cell

 

Education, Training & Credentials

Educational Background

  • PhD, Pharmacology and Toxicology, Medical College of Virginia/Virginia Commonwealth University, Richmond, VA, 1988
  • BS, Pharmacy, University of Toledo, Toledo, OH, 1983

 

Memberships

  • Standing Member, NIH Innate Immunity and Inflammation (III) Study Section, 2013–2017
  • Member, American Association of Immunologists
  • Member, American Association for the Advancement of Science
  • Member, Society for Natural Immunity
  • Director, Cell Culture Facility, Fox Chase Cancer Center
  • Member, Chair, FCCC Facilities Parent Oversight Committee
  • Member, FCCC Facility Advisory Committees
  • Review Editor, Frontiers in NK Cell Biology
  • Member, Cancer Immunotherapy Consortium (Cancer Research Institute)
Research Profile

Research Program

Research Interests

Human natural killer (NK) cells and cancer

  • Molecular mechanisms regulating the function of killer cell Ig-like receptors (KIR)
  • Profiling the phenotype and function of NK cells in cancer patients
  • Therapeutic antibodies to target antitumor responses by human NK cells

Lab Overview

Natural killer (NK) cells constitute about 10-15% of the normal lymphocytes in human peripheral blood. They are important sentinels of the innate immune system that can detect and kill tumor cells and virus-infected cells, and produce cytokines, including interferon-γ and tumor necrosis factor-α. NK cells are regulated by a dynamic balance between positive and negative intracellular signals that are transduced from cell surface activating and inhibitory receptors. This makes them an ideal cellular model system to study signal transduction crosstalk. Our goal is to understand the molecular mechanisms by which NK cells recognize and attack abnormal cells in the body, but are tolerant toward normal cells. This knowledge should lead to therapeutic strategies that can enhance NK cell responsiveness toward tumors and viruses in patients.

Killer cell immunoglobulin-like receptors (KIRs) are key regulators of human NK cell function. KIRs bind major histocompatibility complex class I (MHC-I) molecules on the surfaces of all healthy normal cells in the body. Upon detecting MHC-I, KIRs transduce a negative intracellular signal that suppresses NK cell killing responses. The inhibitory signal derived when KIR detect MHC-I is important for establishing tolerance toward normal cells. Many abnormal tumor cells and virally infected cells eliminate MHC-I expression, however, which abolishes the KIR negative signals and releases the NK cells to specifically attack only these abnormal cells and eliminate them from the body. We are studying the molecular mechanisms controlling the function and surface expression of KIRs. Improved understanding of the regulation of KIR should lead to therapeutic treatments to lower the NK cell activation threshold to more efficiently attack tumor cells and virus-infected cells.

In addition, we are also studying the contributions of NK cells in immune responses toward cancer.  Multiparametric flow cytometry is being employed to study the phenotype and function of NK cells in the peripheral blood of cancer patients.  Current patient cohorts under study include indolent B cell lymphoma, renal cell carcinoma, and multiple myeloma.  Immunotherapies that enhance NK cell function to treat cancer are also under study, including therapeutic antibodies targeting PD-1, KIR, and SLAMF7.  We are characterizing mechanisms by which these antibodies enhance NK cell antitumor responses through blocking inhibitory pathways or initiating antibody dependent cellular cytotoxicity (ADCC) responses.

People

Alexander Macfarlane, PhD

Research Associate

Room: R490
215-728-7762

Ashley Mentlik-James, PhD

Postdoctoral Fellow

Room: R490
215-728-7762

Mohammed Haseebuddin, MD

Surgical Oncology Fellow

Room: R490
215-728-7762

Tatiana Pazina, BS

Graduate Student

Room: R490
215-728-7762

Poliana Patah, MD

Graduate Student

Room: R490
215-728-7762

Anna Thum, BS

Scientific Technician I

Room: R490
215-728-7762

Former staff members
Sei-ichi Yusa, PhD
Akiko Kikuchi-Maki, PhD
Nikolay Gresko, MD, PhD
Diana A. Alvarez Arias, PhD
Yingying Chen, MD, PhD, SM
Shahjahan Miah, PhD
Margaret M. Joyce, PhD
Michael Brusilovsky, PhD
Jun Hasegawa, PhD
Amanda K. Purdy, PhD

Publications

Selected Publications

Brusilovsky, M., Radinsky, O., Cohen, L., Yossef, R., Shemesh, A., Braiman, A., Mandelboim, O., Campbell, K.S. and Porgador, A. (2015) Regulation of natural cytotoxicity receptors through interactions with heparin sulfate proteoglycans in -cis: a lesson from NKp44. Eur. J. Immunol., 45:1180-1191. PubMed

Purdy, A.K., Alvarez-Arias, D.A., Oshinsky, J., James, A.M., Serebriiskii, I., and Campbell, K.S. (2014) The AP-2 clathrin adaptor mediates endocytosis of an inhibitory killer cell Ig-like receptor (KIR) in human NK cells. J. Immunol., 193:4675-4683. PubMed

MacFarlane 4th, A.W., Jillab, M., Plimack, E.R., Hudes, G.R., Uzzo, R.G., Litwin, S., Dulaimi, E., Al-Saleem, T., and Campbell, K.S. (2014) PD-1 expression on peripheral blood cells increases with stage in renal cell carcinoma patients and is rapidly reduced after surgical tumor resection. Cancer Immunol. Res., 2:320-331. PubMed

Mentlik James, A., Cohen, A.D., and Campbell, K.S. (2013) Combination therapies to enhance anti-tumor responses by NK cells. Front. Immunol., 4:481. PubMed

Brusilovsky, M., Cordoba, M., Rosental, B., Hershkovitz, O., Andrake, M.D., Pecherskaya, A., Einarson, M.B., Zhou, Y., Braiman, A., Campbell, K.S., and Porgador, A. (2013) Genome-wide siRNA screen reveals a new cellular partner of NK cell receptor KIR2DL4: heparan sulfate directly modulates KIR2DL4-mediated responses. J. Immunol., 191:5256-5267. PubMed

Campbell, K.S., and Hasegawa, J. (2013) NK cell biology: an update and future directions. J. Allergy Clin. Immunol., 132:536-544. PubMed

Grier, J.T., Forbes, L.R., Monaco-Shawver, L., Oshinsky, J., Atkinson, T.P., Moody, C., Pandey, R., Campbell, K.S., and Orange, J.S. (2012) Human immunodeficiency-causing mutation defines CD16 in spontaneous NK cell cytotoxicity. J. Clin. Invest., 122:3769-3780. PubMed

Campbell, K.S., and Purdy, A.K. (2011) Structure/Function of Human Killer Cell Ig-like Receptors: Lessons from Polymorphisms, Evolution, Crystal Structures, and Mutations. Immunology, 132:315-325. PubMed

Miah, S.M.S., Purdy, A.K., Rodin, N.B., MacFarlane 4th, A.W., Oshinsky, J., Alvarez-Arias, D.A., and Campbell, K.S. (2011) Ubiquitylation of an internalized killer cell Ig-like receptor by Triad3A disrupts sustained NF-kappaB signaling. J. Immunol., 186:2959-2969. PubMed

Purdy, A.K. and Campbell, K.S. (2009) SHP-2 expression negatively regulates NK cell function. J. Immunol. 183:7234-7243. PubMed

MacFarlane 4th, A.W., Yamazaki, T., Fang, M., Sigal, L.J., Kurosaki, T., and Campbell, K.S. (2008) Enhanced NK cell development and function in BCAP-deficient mice. Blood 112:131-140. PubMed

Miah, S.M.S., Hughes, T.L., and Campbell, K.S. (2008) KIR2DL4 differentially signals downstream functions in human NK cells through distinct structural modules. J. Immunol. 180: 2922-2932. PubMed

Alvarez-Arias, D.A., and Campbell, K.S. (2007) Protein kinase C regulates expression and function of inhibitory killer cell Ig-like receptors in NK cells. J. Immunol. 179: 5281–5290. PubMed

Kikuchi-Maki, A., Catina, T.L., and Campbell, K.S. (2005) Cutting Edge: KIR2DL4 transduces signals into human NK cells through association with Fc receptor gamma protein. J. Immunol., 174:3859-3863. PubMed

Additional Publications

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