My research interests fall into two general areas: vascular and skeletal muscle physiology. Vascular endothelial dysfunction is a feature of many cardiovascular disease (CVD) states, and often is a very early occurrence in the disease progression. Specifically, the bio-activity of nitric oxide (NO), an endothelium-derived molecule that is important in vasodilation, in preventing thrombosis, and in preventing inappropriate vascular smooth muscle growth, is compromised in many CVD. The vascular research examines mechanisms controlling nitric oxide bio-availability and function. Specifically, I am interested in how the vascular cell pro- and anti-oxidant balance (oxidative stress) is altered by diet, exercise, gender, and drugs and how these factors alter endothelium-dependent NO-mediated function in otherwise healthy individuals and in those with CVD risk factors such as hypertension and atherosclerosis. It is an ultimate goal of this research to elucidate mechanisms by which vascular antioxidant capacity can be improved and endothelial function preserved for the prevention and treatment of CVD.
Skeletal muscle is a remarkably plastic tissue; it is capable of very impressive changes in phenotype in response to altered activity, and other stimuli. For instance in response to aerobic exercise training, skeletal muscle mitochondrial capacity, capillarity, oxidative enzymes, and ability to transport and utilize metabolic substrates can be greatly enhanced. Conversely, inactivity can reduce the capacity of these systems. It is becoming recognized that as a result of CVD states significant skeletal muscle adaptations can occur, which impair function. These can be the cause of considerable morbidity, and can indirectly accelerate disease progression because of the physical inactivity that they promote. The skeletal muscle research focuses on the roles of nitric oxide, reactive oxygen species and AMP-activated protein kinase on skeletal muscle function and gene expression. The influence of these pathways in the adaptations of skeletal muscle to exercise training and during chronic heart failure are of particular interest. An ultimate goal of this research is to determine novel mechanisms for positive influences of exercise and drugs in the prevention and treatment of skeletal muscle dysfunction that accompanies CVD.