Position title: Associate Professor
Phone: (608) 263-6176
1300 University Ave
Madison, WI 53706
PhD Organic Chemistry, University of New Orleans, New Orleans, LA
Fellowship in Molecular Virology, Louisiana State University Health Sciences
3D chromatin architecture and DNA virus transcriptional control; epigenetic regulation of lifelong viral infections; gene therapy and gene delivery
Viruses are disease-causing obligate intracellular parasites. Upon infection, they hijack cellular pathways to ensure their own survival and spread. Viruses with DNA genomes adopt a genomic structure similar to the chromatin that protects and regulates host cellular chromosomes. Chromatin is comprised of DNA wrapped around histone proteins marked by specific epigenetic post-translational modifications (e.g. phosphorylation, acetylation and methylation) that regulate gene transcription and repression. Chromatin can also regulate transcription through the formation of higher order structures known as three-dimensional loops created and controlled by the interaction of chromatin bound proteins that can be separated by large linear distances. Our laboratory studies how the chromatin structure of viral genomes is established and how it regulates viral infections in hopes of using that knowledge to cure or treat viral infections. The major focus of my laboratory is understanding how the three-dimensional structure of the Herpes Simplex Virus Type 1 (HSV-1) genome controls its transcription.
HSV-1 infects more than 70% of the population, establishes latency in sensory neurons and can reactivate and cause recurrent disease, particularly in the eye, where it is a leading infectious cause of blindness worldwide. Antivirals inhibit HSV-1 productive (lytic) replication but do not target latent reservoirs and therefore novel treatments that impact latency for HSV-1 are needed. In order to produce these therapies, we need a better understanding of how HSV-1 latency works on a molecular level. My laboratory has had a significant impact in this field by discovering that HSV-1 latency is controlled by epigenetic mechanisms established by the three dimensional loop structure of the viral genome. Our technical innovations with AAV have revolutionized our ability to study individual host and viral proteins in infected animals, and have broad implications in gene therapy and the treatment of ocular HSV-1 keratitis, making our work highly translational.