Program in Integrative Sarcomere Signaling

R John Solaro

Director: R. John Solaro, PhD
Distinguished University Professor
Director, Center for Cardiovascular Research

The primary goal of the Program in Integrative Sarcomere Signaling is to understand the fundamental mechanisms responsible for switching the molecular motors of heart muscle cells on and off and for controlling their rates and intensity of activity. These motors are housed in structures called sarcomeres that contain myofilaments responsible for the force development and shortening of heart muscle that is responsible for ejection of blood. This fundamental understanding requires detailed knowledge of the sarcomeric proteins, which we investigate employing the tools of modern proteomics. Sarcomeres also contain a network of proteins that sense mechanical and chemical signals and transduce these signals in the control of dynamics and growth of the sarcomeres. Our experiments address the following questions: What events signal switch function and how is the switch modified by myofilament structure, chemistry, mechanical state in healthy and disordered hearts? How do the myofilaments and proteins of the sarcomeres grow and assemble in response to changing demands for blood flow in health and disease? We approach these questions at the level of the organ and organism by integrating information derived from techniques using the disciplines of biophysics, biochemistry as well as molecular, structural and cellular biology. A significant goal is to translate these studies to improved understanding of acquired and inherited heart failure, especially the linkage of sudden death in the young to mutations in sarcomeric proteins. An important endpoint and success of our approaches has been the development of new drugs for use in the treatment of heart failure.