Research in my laboratory is focused on understanding the protein kinase C signaling cascade and its role in modulating cardiac contractile function. Several endeogenous stimuli activate PKC in the myocardium under physiological conditions, and there is evidence suggesting chronic pathophysiological conditions, including ischemia and heart failure are associated with increases in PKC isoform expression and activation. Our studies focus on structure-function analysis of the heart using adenoviral-mediated gene transfer of constructs into adult cardiac myocytes and into intact myocardium. Using this approach, our work is now focused on understanding the role played by an important target protein for PKC known as troponin I (TnI) and the influence of TnI phosphorylation on cardiac contractile performance. Troponin I is a molecular switch protein located within the sarcomeric thin filament of myocytes, and a phosphorylation target for several signaling pathways. Other studies in my laboratory are directed toward investigating the role played by individual PKC isoforms in modulating contractile function under physiological and pathophysiological conditions. Our recent work has demonstrated a clear role for PKC-mediated cTnI phosphorylation in accelerating relaxation, and identified new phosphorylation targets for PKC isoforms within the heart. In the future, we plan to develop vector delivery of TnI and PKC constructs to failing hearts as a means of restoring cardiac performance.

Related Websites

• Westfall Research Laboratory