Credentials: Medicine Department
Position title: Transcription, Growth Transformation, Notch Signaling
Phone: (608) 262-9952
6531 Wi Institute Medical Research
1111 Highland Ave
Madison, WI 53705
Virology; Transcriptional Mechanisms
I study the role of EBV nuclear proteins in B lymphocyte transformation and EBV biology. Much of my work has been focused on understanding the complex interactions between these proteins and the cell transcription factor RBP-Jk. Remarkably 4 of the 6 EBV nuclear antigens (EBNAs) expressed during latent infection of B cells interact with this DNA binding protein in the Notch signalling pathway. EBNA2 acts much like a ligand indepent Notch protein, activating viral and cell gene expression by targeting RBP-Jk bound to promoters. The other three proteins (EBNA3A, EBNA3B, and EBNA3C) are more subtle in their effects and may destabilize RBP-Jk binding to DNA. For a long time it was unclear if the EBNA3-RBP-Jk interactions were important at all. Our recent genetic evidence has shown that EBNA3A and EBNA3C must each interact with RBP-Jk binding for B lymphocyte transformation to occur. However, it remains unclear what molecular events are downstream of EBNA3 binding to RBP-Jk. In particular, are these complexes associated with promoters and why are both EBNA3A and EBNA3C required for growth transformation while EBNA3B is not?