Drugging the epigenome to reverse pathologic cell states
Our lab is proud to be part of the Division of Cardiovascular Medicine at Vanderbilt University Medical Center. Within this interdisciplinary scientific environment our research explores how chromatin-dependent signaling drives vascular and metabolic disease.
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.
We are proud to have received funding support for our research programs from the National Institutes of Health, Novartis Pharmaceuticals, the American Heart Association, the Vanderbilt-Ingram Cancer Center (VICC) Young Ambassadors and the Vanderbilt Digestive Disease Research Center (VDDRC).
Some of the methods we've been using lately in the lab.
ADIPOSE TISSUE IMAGING
Measuring ectopic fat accumulation
Magnetic Resonance Imaging to identify adipose tissue accumulation during high fat feeding in mice