Grant: Fellowship: Bisby (Prize)

Hypertrophic cardiomyopathy is a genetic disorder of heart muscle and affects approximately 1 in 500 individuals. Hypertrophic cardiomyopathy is characterized by thickening of the heart muscle (hypertrophy) in the main pumping chamber of the heart and leads to poor heart function. Hypertrophic cardiomyopathy is also associated with risk of sudden death and is the most common cause of sudden death in young athletes. Genetic mutations are commonly found in proteins found in the sarcomere, which is the fundamental unit of contraction in a heart cell. Despite our ability to detect affected individuals and associated gene mutations, we do not fully understanding of how sarcomeric mutations lead to hypertrophic cardiomyopathy and poor pumping function of the heart. In addition, we lack targeted therapies aimed at halting or slowing the progression of hypertrophic cardiomyopathy. Our goal is to investigate how individual sarcomeric mutations found in people with hypertrophic cardiomyopathy lead to changes in heart function. Using heart cells taken from patients with hypertrophic cardiomyopathy, we will investigate how heart cells function. We will compare heart cells from hypertrophic cardiomyopathy to heart cells from patients with other heart conditions who are undergoing cardiac surgery. To understand how abnormal heart pump function happens in hypertrophic cardiomyopathy, we will first investigate how different mutations causing hypertrophic cardiomyopathy lead to abnormal contraction in the heart cell. We will also investigate how calcium, which initiates cell contraction, is abnormal in different mutations causing hypertrophic cardiomyopathy. We hope that these experiments will help understand the disease and lead to better therapies.