Our laboratory takes molecular approaches to gene regulation and protein function during herpesvirus replication and latency. We conduct these studies to provide excellent models for biological processes in eukaryotic cells and, because herpesviruses are important pathogens, to exploit differences between herpesvirus and cellular processes for safe and effective antiviral therapy. Areas of research include:
Novel post-transcriptional regulatory mechanisms. Projects include exploring microRNAs, regulated polyadenylation, ribosomal frameshifting, internal ribosome entry sites (IRES's), and translational regulation during herpes simplex virus (HSV) infection.
Herpesvirus DNA replication proteins: antiviral drug targets and prototypes for human replication proteins. Projects include determining the 3-D structures of these proteins (with the Hogle lab) and exploring their interactions with each other and nucleic acids via biochemical, mutational, and biophysical approaches, including (with the Golan and van Oijen labs) single molecule methods. These studies should permit detailed understanding of these complicated proteins and rational drug design.
Drug targets and development of new therapies. Aside from studies of herpesvirus DNA replication proteins, projects include exploiting for drug discovery the human cytomegalovirus protein kinase that phosphorylates the nucleoside analog ganciclovir and the important cellular proteins Rb and lamin A/C investigating how it promotes replication of the virus, and finding new drug targets by a combination of "chemical genetic" and molecular genetic approaches.
HSV latency/pathogenesis. HSV forms latent infections that persist for the life of the host. How this occurs is biologically fascinating and clinically important. Projects entail mutant construction, and PCR-based and microarray methods to explore viral gene regulation (e.g. how microRNAs repress viral gene expression, thereby maintaining latency), and neuronal genes whose expression is altered during viral latency.
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