CURRENT PROJECTS

VASCULAR  AGING AND HUTCHINSON-GILFORD PROGERIA SYNDROME

Age is a major risk factor for cardiovascular disease. Hutchinson-Gilford Progeria Syndrome is a rare genetic disease involving the Lamin A (LMNA) gene that results in premature vascular aging and atherosclerosis early in life. This project aims to develop novel therapies targeting production of the mutant lamin protein called progerin. In addition, ongoing work is exploring how progerin dysregulates transcription and gene expression via alterations in chromatin structure. (Image courtesy of The Progeria Research Foundation).

INFLAMMATION AND ATHEROSCLEROSIS

Inflammation is a central pathogenic mechanism that drives atherosclerosis. Our group has identified that BET bromodomain-containing proteins—bona fide transcriptional coactivators—regulate the inflammatory cell state in atherosclerosis. Furthermore, small molecule inhibition of BET bromodomains can reverse lesion size, suggesting cell state can be drugged.  This project seeks to advance our understanding of how BETs regulate  transcription in the vasculature during atherosclerotic lesion formation and progression.

CORE REGULATORY CIRCUITRY IN FATTY LIVER DISEASE

Nonalcoholoic fatty liver disease (NAFLD) is one of the most common causes of cirrhosis in Western society. In addition, NAFLD is associated with multiple systemic defects including insulin resistance, obesity and cardiovascular disease. This industry sponsored project with Novartis utilizes profiles of the liver epigenome and transcriptome to discover the transcription factor circuits that drive the development of fatty liver disease and progression to hepatic fibrosis in humans.