McKinsey Lab – Epigenetic Regulation of Heart Failure
Our lab is focused on understanding the signaling and gene regulatory mechanisms that control heart failure and associated disorders. We are particularly interested in the role of epigenetics in regulating the pathological cardiac hypertrophy and fibrosis that is associated with heart failure. Nuclear DNA is wound around proteins called histones to form chromatin, and post-translational modification of histones represents one epigenetic mechanism for altering gene expression. Among the enzymes that target histones are histone deacetylases (HDACs), histone acetyltransferases (HATs) and histone methyltransferases. We use molecular biology, biochemistry and pharmacology to address the roles of these and other epigenetic modifiers in the control of gene expression in the heart, and extend our findings to surgical, transgenic and gene knockout models of heart failure. Our animal model studies involve echocardiographic and catheter-based measurements of heart function. We are also interested in the mechanisms whereby signals derived from cell surface receptors are conveyed to histone-modifying enzymes by proteins kinases and phosphatases. The long-term goal of our work is to translate basic discoveries to novel therapies for patients with heart failure, which afflicts millions of adults in the U.S. and is associated with a 5-year mortality rate of nearly 50%. As such, our lab has established core expertise to enable in vitro, cellular and in vivo assessment of experimental small molecule compounds in support of early stage drug discovery. Our lab emphasizes teamwork and camaraderie, thus creating an exciting environment for students and postdoctoral trainees.
Timothy A. McKinsey, Ph.D.
Department of Medicine, Division of Cardiology
University of Colorado Denver
Anschutz Medical Campus
12700 E. 19th Ave
Aurora, CO 80045-0508
Tel: (303) 724-5476