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Kerry S. Campbell, PhD

Kerry S. Campbell, PhD
About

Research Program

Polarization of the NK cell tubulin cytoskeleton (green; GFP-tubulin) toward a tumor target cell (red) at 1, 4, and 12 minutes (left to right). Thanks to Amanda Purdy, Ph.D.
Orientation of the NK cell microtubule organizing center (MTOC; red, marked by pericentrin) and cytolytic granules (blue, marked by perforin) toward a tumor target cell
Campbell Lab 2010 (left to right): Mowafaq Jillab, MD, Alexander MacFarlane, PhD, Amanda Purdy, PhD, Michael Brusilovsky, Margaret Joyce, PhD, Jennifer Oshinsky, Kerry Campbell, PhD, Nicholas Rodin
Campbell Lab 2013 (#1) (left to right): Poliana Patah, MD, Jun Hasegawa, PhD, Alexander MacFarlane, PhD, Ashley James, PhD, Kerry Campbell, PhD, Tatiana Pazina, Amanda Purdy, PhD, Jennifer Oshinsky
Campbell Lab 2013 (#2) “Levitating” (left to right): Poliana Patah, MD, Jun Hasegawa, PhD, Alexander MacFarlane, PhD, Ashley James, PhD, Kerry Campbell, PhD, Tatiana Pazina, Amanda Purdy, PhD, Jennifer Oshinsky
Campbell Lab 2017 (#1): Standing: Alexander MacFarlane, PhD, Dmitry Zhigarev, Kerry Campbell, PhD, Sanjna Shelukar, Tatiana Pazina; Sitting: Chun Zhou, PhD, Kimberly Branigan Colby, Irina Shchaveleva
Campbell Lab 2017 (#2) (left to right): Kimberly Branigan Colby, Chun Zhou, PhD, Sanjna Shelukar, Alexander MacFarlane, PhD, Kerry Campbell, PhD, Dmitry Zhigarev, Tatiana Pazina; Sitting: Irina Shchaveleva

 

Education and Training

Educational Background

  • Independent Member, Basel Institute for Immunology, Basel, Switzerland, 1998
  • Post-Doctoral Training, National Jewish Research Center, Denver, CO, 1992
  • 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
  • Member, American Association of Cancer Research
  • Member, American Society of Hematology
  • Chair, FCCC Facilities Parent Oversight Committee
  • Member, FCCC Facility Advisory Committees
  • Review Editor, Frontiers in NK and Innate Cell Biology, and Cancer Immunity and Immunotherapy
  • 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.  We are also currently collaborating with a psychologist at FCCC, Dr. Carolyn Fang, to establish relationships over time between psychosocial functioning and immune phenotype and function in indolent B cell lymphoma patients. 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, co-stimulating, or initiating antibody dependent cellular cytotoxicity (ADCC) responses.

Former staff members
Sei-ichi Yusa, PhD
George Hii, B.S.
Tracey L. Catina-Hughes, B.S.
Akiko Kikuchi-Maki, PhD
Nikolay Gresko, MD, PhD
Diana A. Alvarez Arias, PhD
Yingying Chen, MD, PhD, SM
S. M. Shahjahan Miah, PhD
Margaret M. Joyce, PhD
Nicholas Rodin, B.S.
Jennifer Oshinsky, B.S.
Michael Brusilovsky, PhD
Mowafaq Jillab, M.D.
Jun Hasegawa, PhD
Amanda K. Purdy, PhD
Poliana Patah, M.D., Ph.D.
Anna Thum, B.S.
Ashley Mentlik James, Ph.D.
Mohammed Haseebuddin, M.D.

Lab Staff

Alexander Macfarlane, PhD

Research Associate

Room: R490
215-728-7762

Tatiana Pazina, PhD

Postdoctoral Associate

Room: R490
215-728-7762

Dmitry I. Zhigarev, BS

Graduate Student

Room: R490
215-728-7762

Judy Fang

Scientific Technician I

Room: R490
215-728-7762

Irina L. Shchaveleva, MS

Scientific Technician II

Room: R490
215-728-7762

Kimberly Branigan, BS

Scientific Technician I

Room: R490
215-728-7762
Publications

Selected Publications

Wagner J, Kline CL, Zhou LL, Campbell KS, MacFarlane AW, Olszanski AJ, Cai KQ, Hensley HH, Ross EA, Ralff MD, Zloza A, Chesson CB, Newman JH, Kaufman H, Bertino J, Stein M, El-Deiry WS. Dose intensification of TRAIL-inducing ONC201 inhibits metastasis and promotes intratumoral NK cell recruitment. Journal of Clinical Investigation, 128(6):2325-38, 2018.  PubMed

MacFarlane 4th, A.W., Jillab, M., Smith, M.R., Alpaugh, R.K., Cole, M., Litwin, S., Millenson, M.M., Al-Saleem, T., Cohen, A.D.,* and Campbell, K.S.* (2017) NK Cell Dysfunction in Chronic Lymphocytic Leukemia is Associated with Loss of the Mature Cells Expressing Inhibitory Killer Cell Ig-like Receptors, Oncoimmunology, 6:e1330235. PMCID: 5543845. *Corresponding authors. tandfonline.com

Pazina, T., James, A.M., MacFarlane IV, A.W., Bezman, N.A., Henning, K.A., Bee, C., Graziano, R.F., Robbins, M.D., Cohen, A.D. *, and Campbell, K.S. * (2017) The anti-SLAMF7 antibody elotuzumab mediates NK cell activation through both CD16-dependent and –independent mechanisms, Oncoimmunology, in press. *Corresponding authors. tandfonline.com

Davis, Z.B., Cogswell, A., Hamish, S., Mertsching, A., Boucau, J., Wambua, D., Le Gall, S., Planelles, V., Campbell, K.S., and Barker, E. (2016) A conserved HIV-1-derived peptide presented by HLA-E renders infected T-cells highly susceptible to attack by NKG2A/CD94-bearing natural killer cells. PLoS Pathog, 12:e1005421. *Highlighted in Faculty of 1000. PMCID: 4735451

Shemesh, A., Brusilovsky, M., Hadad, U., Teltsh, O., Edri, A., Rubin, E., Campbell, K.S., Rosental, B., and Porgador, A. (2016) Survival in acute myeloid leukemia is associated with NKp44 splice variants. Oncotarget, 7:32933-32945. PMCID: 5078064.

Pazina, T., Shemesh, A., Brusilovsky, M., Porgador, A., and Campbell, K.S. (2017) Regulation of the functions of natural cytotoxicity receptors by interactions with diverse ligands and alterations in splice variant expression. Front. Immunol., 8:369, PMCID: 5371597.

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. PMCID: 4415513.

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. PMCID: 4007343.

Anikeeva, N., Steblyanko, M., Fayngerts, S., Kopylova, N., Marshall, D., Powers, G.D., Sato, T., Campbell, K.S., and Sykulev, Y. (2014) Integrin receptors on tumor cells facilitate NK cell-mediated antibody-dependent cytotoxicity. Eur. J. Immunol., 44:2331-2339. PMCID: 4141007.

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. PMCID: 4269369.

Campbell, K.S., and Hasegawa, J. (2013) NK cell biology: an update and future directions. J. Allergy Clin. Immunol., 132:536-544, PMCID: 3775709.

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. PMCID: 3836631.

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, PMCID: 3870292.

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. PMCID: 3461929.

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-kB signaling. J. Immunol., 186:2959-2969. PMCID: 3079396.

Additional Publications

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