Associate Professor, Department of Microbiology
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.
Course Director, Introduction to Research
PhD from University of London
Fellowship, Cold Spring Harbor Laboratory, NY, Molecular Biology
Proceedings of the National Academy of Sciences of the United States of America (PNAS). 2021 Jul 27; 118(30):
Genes & development. 2021 07 01; 35(13-14):1005-1019
Nature communications. 2020 11 26; 11(1):6016
Current protocols in microbiology. 2020 Jun; 57(1):e99
Journal of neurovirology. 2020 Apr; 26(2):297-309
Methods in molecular biology. 2020 Oct; 2060:263-277
Molecular cell. 2019 May 02; 74(3):466-480.e4
Nature communications. 2019 Feb 14; 10(1):754