Heart disease remains the leading cause of death in the United States and other developed countries. Half of these deaths occur suddenly, typically from ventricular tachyarrhythmias that arise in the setting of acute ischemia, acquired heart disease or inherited syndromes including channelopathies and cardiomyopathies. Despite decades of research, major gaps exist in our understanding of the molecular mechanisms responsible for normal cardiac rhythmicity, as well as abnormalities that increase the risk of rhythm disturbances. Our laboratory has identified molecules, known as fibroblast growth factor homologous factors (FHFs), that potently regulate heart rhythm. In the absence of FHFs, hearts develop significant conduction disease and arrhythmias. In this application we propose a series of experiments designed to understand the mechanisms through which deficiency of FHF proteins results in these disease manifestions.
Heart disease is the leading cause of death in the United States and other developed countries and almost half of these deaths occur suddenly from heart rhythm abnormalities. Our research is directed toward understanding the mechanisms responsible for normal and abnormal heart rhythms and identifying potential new therapeutic targets. This project focuses on the role of fibroblast growth factor homologous factor (FHF) proteins as regulators of cardiac rhythmicity in health and disease.
