Brett A. Colson, PhD

The research goal of my laboratory is to understand the molecular motions of muscle proteins that finely-tune the heart’s contractile performance. We then use these insights from our mechanistic studies to design novel molecular therapies for heart failure and cardiovascular disease. Using site-directed spectroscopy, with high resolution in both space and time, we decipher the molecular dynamics in these proteins involved with controlling the strength and speed of cardiac muscle contraction. We attach fluorescent probes to track protein motions and myosin cross-bridge orientation in muscle fibers, and assess the associated functional characteristics including protein binding and force development in the muscle cell. The primary focus of our current research is to understand the relationship between the structural and biochemical transitions in cellular and molecular mechanisms underlying dysfunction in muscle disease. Specifically, how genetic mutations in myosin binding protein-C (MyBP-C) cause the development of hypertrophic cardiomyopathy, leading to arrhythmias, heart failure, and sudden cardiac death. Current research projects in my lab also include spectroscopic studies of actin and myosin structural dynamics related to other human physiology and disease phenomena, such as post-translational modifications in the fight-or-flight stress response (beta-adrenergic signaling) and roles of sex hormones in aging (muscle weakness and metabolism).