We are very interested in how the molecular and cellular biology of the heart cell impacts the contractile properties of the intact heart. We know that a number of factors influence gene expression and cell signaling in the cardiac myocyte including diet, exercise, disease and sex/gender. The changes induced by these factors will ultimately affect cardiac contractile function. It is this functional relationship that we are studying using a variety of molecular, cellular, and physiological techniques. We focus on the intermediates responsible for substrate utilization and presentation to the contractile apparatus. We hope to understand how the physiological factors of diet, exercise, disease and sex/gender impact substrates in the cell and how the presentation of these substrates affects contractile function.We are also interested in how cardiac disease can influence peripheral organ systems including skeletal muscle. We know that humans with cardiac disease also experience severe skeletal muscle weakness and fatigue. This cannot be attributed entirely to poor circulation caused by reduced contractile function. Instead, we believe that is the specific alteration of specific muscle factors responsible for substrate metabolism and delivery to the muscle cell.