Our lab focuses on understanding the molecular mechanisms underlying herpes simplex virus (HSV) latency and reactivation. These processes are central to the human disease caused by this virus. Our research efforts encompass many approaches, from in vitrobiochemical and molecular studies to the development and utilization of refined in vivomodel systems.
Recently, we have made an observation that shifts the HSV reactivation paradigm, identifying an essential role for the viral tegument protein VP16 in the earliest stages of HSV reactivation in neurons in vivo.
Several ongoing projects stem from this observation:
- Through a molecular analysis of the VP16 promoter, we are determining how VP16 expression is regulated from the latent viral genome in the nervous system. This project will lead us to an understanding of the host cell factors that initiate the lytic cycle from the latent viral genome.
- We are testing the hypothesis that phosphorylation of VP16 at serine 375 is critical for VP16 cofactor interactions necessary for driving reactivation from latency.
- We are beginning the process of translating our basic discovery into much-needed treatments for HSV disease.
Our additional areas of investigation include:
- The mechanisms underlying the silencing of viral gene expression in the nervous system by the HSV LAT locus and by the host protein Trim19
- Identification and characterization of disease resulting from chronic HSV latency / reactivation cycles in the CNS
- Identification of host genes and pathways contributing to susceptibility and resistance to HSV disease outcomes utilizing advanced recombinant inbred (ARI) strains of mice.