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. Splice variants of human natural cytotoxicity receptors: novel innate immune checkpoints
  2. The anti-SLAMF7 antibody elotuzumab mediates NK cell activation through both CD16-dependent and –independent mechanisms
  3. NK cell dysfunction in chronic lymphocytic leukemia is associated with loss of the mature cells expressing inhibitory killer cell Ig-like receptors
  4. Regulation of the functions of natural cytotoxicity receptors by interactions with diverse ligands and alterations in splice variant expression
  5. Expression of NKp46 splice variants in nasal lavage following respiratory viral infection: Domain 1-negative isoforms predominate and manifest higher activity
  6. Targeted delivery of chemotherapy using HSP90 inhibitor drug conjugates is highly active against pancreatic cancer models
  7. Haploinsufficiency in tumor predisposition syndromes: Altered genomic transcription in morphologically normal cells heterozygous for VHL or TSC mutation
  8. Survival in acute myeloid leukemia is associated with NKp44 splice variants
  9. Suppressing the killer instinct
  10. Erratum: Cutting edge: Role of NK cells and surfactant protein D in dendritic cell lymph node homing: Effects of ozone exposure (Journal of Immunology (2016) 196 (553-557))
  11. 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
  12. Cutting edge: Role of NK cells and surfactant protein D in dendritic cell lymph node homing: Effects of ozone exposure
  13. MTOR-dependent and independent survival signaling by PI3K in B lymphocytes
  14. NKp44 and NKp30 splice variant profiles in decidua and tumor tissues: A comparative viewpoint
  15. An NK cell line (haNK) expressing high levels of granzyme and engineered to express the high affinity CD16 allele
  16. Central nervous system acute lymphoblastic leukemia: Role of natural killer cells
  17. Integrins influence the size and dynamics of signaling microclusters in a Pyk2-dependent manner
  18. Regulation of natural cytotoxicity receptors by heparan sulfate proteoglycans in -cis: A lesson from NKp44
  19. PD-1 expression on peripheral blood cells increases with stage in renal cell carcinoma patients and is rapidly reduced after surgical tumor resection
  20. Carbohydrate-mediated modulation of NK cell receptor function: Structural and functional influences of heparan sulfate moieties expressed on NK cell surface