DF/HCC Program Affiliation

Cancer Cell Biology
Lymphoma and Myeloma

Research Abstract

This central objective of research program is to understand the mechanisms by which Epstein-Barr Virus causes human lymphoma, Hodgkin's Disease, nasopharyngeal cancer, gastric cancer, and other malignancies and to use that knowledge to devise new preventative, diagnostic, and therapeutic stategies.

Our current reserach has lead us to the conclusion that Epstein-Barr Virus uses aspects of the Notch and CD40 receptor signaling pathways to take control of cell growth and to increase cell survival. Given the role of Notch signaling in human T cell leukemia and of CD40 in lymphcyte growth regulation we are studying both the interaction of viral proteins with those pathways and the pathways themselves. Critical steps in these pathways can be exploited for the development of drug targets and such targets, especially NF-kB activation by LMP1 are being validated by genetic, biochemical, and screening studies.
Because of our interest in translational medicine, we are also studying the mechansisms by which EBV replicates and persists in cells and in humans. Current research in these areas involves mapping the interactions among EBV and cell proteins in replication and studies of the EBV perisitence proteins, EBNA1. Chemical screens for inhibitors of EBNA1 have identified several classes of inhibitors.

Publications

• Izumi KM, Cahir McFarland ED, Ting AT, Riley EA, Seed B, Kieff ED.The Epstein-Barr virus oncoprotein latent membrane protein 1 engages the tumor necrosis factor receptor-associated proteins TRADD and receptor-interacting protein (RIP) but does not induce
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