PROJECTS

Elucidating new mechanisms and treatments for cardiac hypertrophy and heart failure

The Kass lab focuses on elucidating novel mechanisms and therapies for various forms of myocardial disease. We utilize animal models with pressure-overload stress, ischemic or infarction stress, neurohormone stimulation, or cytotoxic stress often combined with genetically engineered mice to dissect signaling pathways.  These studies are often coupled with tests of therapeutic approaches, genetic, small molecule, and device-based to identify effective new approaches that might warrant clinical testing and translation. Both hypertrophic heart disease and depressed dilated cardiomyopathy are studied.  The methods used are highly integrative, spanning sub-cellular molecular analysis and assays to cell culture and primary cell physiologic studies, through to intact animal models spanning mouse to human. Human studies make use of endocardial biopsies and explanted human heart tissue  to test signaling pathways and muscle function.  Cell physiology makes use of real-time myocyte shortening/calcium data obtained in unloaded myocytes or adding force in cells that are attached to a loading system. Sarcomere function is examined in chemically permeabilized myocytes, focusing on force-calcium dependence. The lab first developed pressure-volume analysis in intact large animals, then humans, and then mice, and use the method routinely.