Philadelphia, PA 19111-2497
(215) 728-7761
(215) 728-2412 fax
Most Recent Peer-reviewed Publications
- Prohibitins and the cytoplasmic domain of CD86 cooperate to mediate CD86 signaling in B lymphocytes
- Human immunodeficiency-causing mutation defines CD16 in spontaneous NK cell cytotoxicity
- B-cell adaptor for PI3K (BCAP) negatively regulates Toll-like receptor signaling through activation of PI3K
- Proliferating cell nuclear antigen is a novel inhibitory ligand for the natural cytotoxicity receptor NKp44
- Structure/function of human killer cell immunoglobulin-like receptors: Lessons from polymorphisms, evolution, crystal structures and mutations
Medical School
BS, Pharmacy, University of Toledo, Toledo, OH - 1983
PhD, Pharmacology and Toxicology, Virginia Commonwealth University, Richmond, VA
- 1988
Fellowship
Postdoctoral Fellow, National Jewish Center, Denver, CO - 1988-1992
Other Qualifications
Independent Member, Basel Institute for Immunology, Basel, Switzerland - 1992-1998
Associate Member, Fox Chase Cancer Center, Philadelphia, PA - 1998-2004
Associate Professor, 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
Adjunct Associate Professor, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel - 2009-present
Expertise and Research 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.
Other Expertise
Director, Cell Culture Facility, Fox Chase Cancer Center
Keywords
NK Cells, signal transduction, KIR