Our laboratory focuses on the mechanisms by which Epstein-Barr virus activates and ultimately subverts the host oncogenic stress response to growth transform primary B lymphocytes into indefinitely proliferating lymphoblastoid cell lines (LCLs). EBV infection of B cells leads to a latent growth program where eight viral proteins and several non-coding RNAs are expressed. Among these gene products, latent membrane protein 1 (LMP1) and Epstein-Barr virus nuclear antigen (EBNA) 2 are the core transforming oncogenes. These proteins are capable of driving B cell proliferation and act to suppress the apoptotic response induced by aberrant S phase induction. The goals of the laboratory include: i) understanding the host pathways that respond to and suppress EBV-mediated growth transformation, ii) understanding the viral gene products important for activating the oncogenic stress response and ultimately overcoming this response, and iii) identifying and characterizing a cell population within the CD21-expressing primary B cell population that has an increased susceptibility to oncogenic stress.
The biochemical and genetic analyses of these pathways will provide valuable insight into our understanding of oncogenes and oncogenic viruses and the host cell response to such insults. Further, detailed understanding of the virus/host interaction may allow for the identification of specific pathways for therapeutic intervention in EBV-associated malignancies and possibly more broadly in malignancies which rely on similar pathways for their proliferation, survival, or self-renewal.