Philadelphia University + Thomas Jefferson University

Campbell, Kerry

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Kerry S. Campbell, PhD

Kerry S. Campbell, PhD

Contact Dr. Campbell

333 Cottman Avenue
Fox Chase Cancer Center
Philadelphia, PA 19111

(215) 728-7761
(215) 728-2412 fax

Research and Clinical Interests

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.

Publications

Most Recent Peer-Reviewed Publications

  1. Survival in acute myeloid leukemia is associated with NKp44 splice variants
  2. Suppressing the killer instinct
  3. NKp44 and NKp30 splice variant profiles in decidua and tumor tissues: A comparative viewpoint
  4. Central nervous system acute lymphoblastic leukemia: Role of natural killer cells
  5. Integrins influence the size and dynamics of signaling microclusters in a Pyk2-dependent manner
  6. Regulation of natural cytotoxicity receptors by heparan sulfate proteoglycans in -cis: A lesson from NKp44
  7. PD-1 expression on peripheral blood cells increases with stage in renal cell carcinoma patients and is rapidly reduced after surgical tumor resection
  8. Carbohydrate-mediated modulation of NK cell receptor function: Structural and functional influences of heparan sulfate moieties expressed on NK cell surface
  9. The AP-2 clathrin adaptor mediates endocytosis of an inhibitory killer cell Ig-like receptor in human NK cells
  10. Integrin receptors on tumor cells facilitate NK cell-mediated antibody-dependent cytotoxicity
  11. Combination immune therapies to enhance anti-tumor responses by NK cells
  12. Genome-wide siRNA screen reveals a new cellular partner of NK cell receptor KIR2DL4: Heparan sulfate directly modulates KIR2DL4-mediated responses
  13. Natural killer cell biology: An update and future directions
  14. Prohibitins and the cytoplasmic domain of CD86 cooperate to mediate CD86 signaling in B lymphocytes
  15. A novel mechanism for cancer cells to evade immune attack by NK cells: The interaction between NKp44 and proliferating cell nuclear antigen
  16. Human immunodeficiency-causing mutation defines CD16 in spontaneous NK cell cytotoxicity
  17. B-cell adaptor for PI3K (BCAP) negatively regulates Toll-like receptor signaling through activation of PI3K
  18. Proliferating cell nuclear antigen is a novel inhibitory ligand for the natural cytotoxicity receptor NKp44
  19. Structure/function of human killer cell immunoglobulin-like receptors: Lessons from polymorphisms, evolution, crystal structures and mutations
  20. Ubiquitylation of an internalized killer cell Ig-like receptor by Triad3A disrupts sustained NF-kB signaling