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Our laboratory focuses on understanding gene regulation in the cardiovascular system, skeletal muscle, and other metabolic tissues, with the ultimate goal of finding novel therapeutic strategies to prevent and treat cardio-metabolic and -myopathic diseases. A major aspect of our work centers around transcriptional and epigenetic control of plasticity in cardiomyocytes, smooth muscle, and skeletal muscle in physiology and disease. To study these pathways, we use a range of in vitro and in vivo approaches, including manipulating genes in mice and leveraging genome-wide analyses and chemical biology. We have made several important observations through our work. For example, we identified that acetyl-lysine “reader” proteins of the BET family play a critical role in cardiac transcription and heart failure pathogenesis. Importantly, we showed that inhibition of BET proteins using a potent and specific small molecule could treat heart failure in animal models. Over the past decade, we have also demonstrated that the zinc finger transcription factor KLF15 functions as a nodal regulator of cardiovascular plasticity and multi-organ metabolic homeostasis. Collectively, our work has led to novel pathophysiologic and therapeutic insights for diseases, such as heart failure, aortic aneurysms, diabetes, and skeletal myopathies. Because epigenetic regulators and chromatin-associated proteins are often tractable drug targets, my laboratory actively seeks to discover new targets and translate our findings into novel therapeutics for cardiovascular disease.
- Sarnoff Cardiovascular Foundation
- American Heart Association Council on Basic Cardiovascular Sciences
- Cornell University
- John Hopkins University School of Medicine