My laboratory utilizes an integrative approach to study the pathophysiological mechanisms of heart failure, with a specific focus on dystrophic cardiomyopathies. Patients with many forms of muscular dystrophy also have significant cardiac disease. Interestingly, several of the proteins associated with these dystrophic cardiomyopathies have also been implicated in heart failure resulting from more common causes (i.e., ischemic heart disease). Duchenne muscular dystrophy, the most common form of muscular dystrophy, is caused by mutations in the protein dystrophin. Dystrophin is a large protein that spans from the intracellular cytoskeletal actin lattice to a complex of glycoproteins in the sarcolemmal membrane, which in turn binds to the extracellular matrix. It functions both as a mechanical shock absorber and scaffold for a large array of signaling molecules. We study heart disease at varying levels of biological complexity including intact animals, isolated organs, and indivdual adult cardiomyocytes to obtain insights into disease mechanisms. We also probe molecular physiology, utilizing biochemical methodologies, transgenesis, and in vivo gene transfer. This highly integrated approach provides unique insights into the pathophysiology of heart disease and ultimately will enable us to develop novel therapeutic approaches.
