My research is designed to understand the molecular mechanism of how the heart works, how it begins to fail in both inherited and acquired heart disease, and how this understanding can be used to design new treatments for heart disease. I am particularly focused on a type of heart failure known as hypertrophic cardiomyopathy (HCM), a devastating disease that affects about 1 in 500 people worldwide. Since inherited mutations in a specific protein, myosin, are a major cause of this disease, my work focuses on myosin.
In cardiac muscle, length-dependent activation of both myosin and actin contribute to the Frank-Starling mechanism, a primary determinant of cardiac function. Thick filament activation is hypothesized to control the number of force-generating myosin. Myosin is the protein in the heart that acts as a molecular machine, directly providing the force needed for pumping blood. Defects in myosin are a major cause of inherited heart disease. I am devising technology to detect the inner workings of myosin and thus to determine how it works in the heathy heart, and how it fails in heart disease. How does myosin change its shape when the heart needs to relax and when it needs to pump blood? How does this change in heart disease?