My research focuses on transcriptional and post-transcriptional control of gene expression in the context of three viruses that cause disease in humans: herpes simplex virus type 1 (HSV-1), human cytomegalovirus (HCMV), and Kaposi’s sarcoma-associated herpesvirus (KSHV).
HSV-1 is most familiar as the infectious agent responsible for cold sores but it is also a leading cause of blindness and other debilitating diseases. More than 70% of the US population will establish a life-long latent infection with HSV-1 and be at risk for disease when the latent virus reactivates. HSV-1 latency is limited to neurons in the peripheral nervous system and we are working to understanding how neuronal factors control HSV-1 and thereby maintain latency. Fortunately this can be effectively modeled by infecting neurons cultured in the laboratory.
My interest in HSV-1 began almost 25 years ago as a Damon Runyon-Walter Winchell postdoctoral fellow with Winship Herr at Cold Spring Harbor Laboratory. These studies culminated in the biochemical purification and molecular cloning of HCF-1, a component of host chromatin that is coopted by HSV-1 to control viral gene expression. These studies have continued at NYU and in collaboration with the laboratories of colleagues Ian Mohr (Microbiology) and Moses Chao (Skirball Institute Molecular Neurobiology Program) we recently discovered a unique two-step transcription program used by HSV-1 to escape from latency in response to stress signals. Critical antiviral defenses such as interferon, act by selectively blocking the first step in this program (termed Phase I), keeping the virus latent without irrevocably harming the host neuron. Our findings indicate that Phase I is used to produce viral factors needed to replicate the virus in Phase II and to simultaneously antagonize the antiviral defenses triggered by interferon. Rapid initiation of Phase I creates a window of opportunity for the virus to escape host control, replicate and spread to uninfected cells. Current projects aim to (a) understand the mechanisms initiate Phase I, (b) identify host epigenetic factors that suppress viral gene expression to maintain latency and (c) characterize viral factors that push the two-step program forward into Phase II, which culminates in synthesis and spread of new infectious virus.
We are also collaborating with Dimitris Placantonakis (Neurosurgery) to develop new infection models that better recapitulate HSV-1 pathogenesis in humans allowing us to explore innovative strategies to control and ultimately eliminate the virus.
Associate Professor, Department of Microbiology
Course Director, Foundations of Cellular and Molecular Biology
Manager, NYULMC OSR Cold Storage
PhD from University of London
Fellowship, Cold Spring Harbor Laboratory, NY, Molecular Biology
Pathogens. 2017 Jun 8; 6(2):?-?
Cell reports. 2017 Jan 31; 18(5):1312-1323
Journal of virology. 2017 Jan 3; 91(2):?-?
Journal of virology. 2014 Feb; 88(4):2337-2339
Methods in molecular biology. 2014; 1144:167-179
Trends in microbiology. 2012 Dec; 20(12):604-611
Genes & development. 2012 Jul 15; 26(14):1527-1532
Journal of visualized experiments : JoVE. 2012 Apr 2; (62):?-?