Immunology Graduate Group
Gary Koretzky, M.D., Ph.D.
Director of Signal Transduction Program and Investigator,Abramson Family Cancer Research Institute;
Leonard Jarett Professor of Pathology and Laboratory Medicine;
Chief, Division of Rheumatology, Department of Medicine
Address: 415 BRB II/III, 421 Curie Blvd.
Office Phone: (215) 746-5522
Lab Phone: (215) 746-5541/42
Fax: (215) 746-5525
Email: koretzky@mail.med.upenn.edu
Link to Koretzky lab page
M.D., University of Pennsylvania
Ph.D., University of Pennsylvania
Master of Arts (Honorary), University of Pennsylvania
A.B., Cornell University
Research Summary
Gary A. Koretzky , MD, PhD directs the Signal Transduction Program of the Abramson Family Cancer Research Institute and is the Chief of the Division of Rheumatology. His laboratory focuses on understanding the important role T lymphocytes and other cells of the immune system play in combating infection and destroying cancerous tissue. Through specific receptors on their surface, these cells recognize infected or transformed malignant tissue. This recognition stimulates those receptors on the immune cells, initiating a cascade of biochemical events, the process known as signal transduction.
Dr. Koretzky aims to understand how various signal transduction pathways activate immune cells. He has identified several novel proteins that are critical for stimulating the appropriate cellular response. To understand how these proteins act, Koretzky and colleagues have developed mice that lack expression of these proteins or express mutated variants of these molecules. By analyzing these mice the Koretzky team has discovered the contributions played by three key molecules, SLP-76, ADAP and PRAM-1, which facilitate interaction between proteins. By regulating and integrating the intermolecular interactions, these three proteins control both development and function of several immune cell lineages.
More recently the Koretzky laboratory uncovered a novel function for the SLP-76 molecule. In addition to being critical for development and activation of immune cells, this protein is also essential for normal vascular development. Thus, in the absence of SLP-76, lymphatics fail to separate from blood vessels. Understanding how SLP-76 regulates this critical developmental event is an ongoing focus of the laboratory.
Koretzky's work has informed the community about important signaling events which must occur as immune cells develop and function. His work has also provided insights into possible new targets for the development of drugs that modulate immune cell function in the hopes of developing better therapeutic agents.
Background
Gary Koretzky obtained his M.D. and Ph.D. (Immunology) degrees at the University of Pennsylvania, then pursued clinical training in Internal Medicine and Rheumatology at the University of California at San Francisco. He re-entered the laboratory as a postdoctoral fellow, examining the molecular events associated with T cell activation. Dr. Koretzky moved to the University of Iowa in 1991 where he continued his research examining the biochemistry and molecular biology of signal transduction in hematopoietic cells.
Dr. Koretzky joined the faculty at the University of Pennsylvania in 1999 in the Department of Pathology and Laboratory Medicine and as Director of the Signal Transduction Program of the Leonard and Madlyn Abramson Family Cancer Research Institute at the Abramson Cancer Center at the University of Pennsylvania. In addition to his responsibilities within the Abramson Institute, Dr. Koretzky is an Associate Director of the Combined Degree (MD/PhD) Program and is on the Executive Committees of the Graduate Program in Immunology and the Graduate Program in Cellular and Molecular Biology. Dr. Koretzky also serves on the Executive Committee of the University of Pennsylvania Cancer Center and most recently was appointed Chief of the Division of Rheumatology in the Department of Medicine of the University of Pennsylvania School of Medicine. Dr. Koretzky is past President of the American Society for Clinical Investigation, is a Fellow of the American Association for the Advancement of Science, and serves as the Editor in Chief of Immunological Reviews.
Recent Publications
Koretzky, G.A ., Abtahian, F., Silverman, M.A. SLP-76 and BLNK: Complex regulation of signaling in lymphocytes and beyond. Nat. Reviews Immunol. In press.
Maltzman, J.S., Kovoor, L., Clements, J.L. and Koretzky, G.A. Conditional deletion of SLP-76 reveals a cell autonomous requirement for T cell lineage commitment. J. Exper. Med. 202:893-900, 2005. Epub Sep 26.
Nichols, K.E., Hom, J., Gong, S.Y., Ganguly, A., Ma, C.S., Cannons, J.L., Tangye, S.G., Schwartzberg, P.L., Koretzky, G.A. , Stein, P.L. Regulation of NKT cell development by SAP, the protein defective in XLP. Nat. Med. 11:340-45, 2005.
Newbrough, S.A., Mocsai, A., Clemens, R.A., Wu, J.N., Silverman, M.A., Singer, A.L., Lowell, C.A., Koretzky, G.A. SLP-76 regulates Fc g receptor and integrin signaling in neutrophils. Immunity , 19:761-9, 2003.
Abtahian, F., Guerriero, A., Sebzda, E., Lu, M-M., Zhou, R., Mocsai A., Meyers, E.E., Huang, B., Jackson, D., Ferrari, V.A., Tybulewicz, V., Lowell, C.A., Lepore, J.J., Koretzky, G.A. , Kahn. M.L. regulation of blood and lymphatic vascular separation by signaling proteins SLP-76 and Syk. Science , 299:247-251, 2003.
hong, X-P., Hainey, E.A., Olenchock, B.A., Jordan, M.S., Maltzman, J.S., Nichols, K.E., Shen, H., Koretzky, G.A . Enhanced T cell responses due to diacylglycerol kinase z deficiency. Nat. Immunol . 4:882-890, 2003.