The Davis lab is focused on uncovering the mechanistic basis for how the heart heals, repairs, and remodels in response to injury and disease. Toward this end we are tackling a fundamental problem associated with every form of heart disease, which is the replacement of contractile muscle with fibrotic scarring. The presence of fibrotic scar impairs both repair and function of the heart and rapidly accelerates the disease process. We’ve been implementing genome-wide screening and genetic engineering of cells and mice to resolve the signaling networks causal for fibrotic scar formation. Our ultimate goal is to leverage this molecular network to tactically block or regress scar formation in patients thereby slowing the disease process and creating an environment more amenable to regenerative therapies.
Equally problematic drivers of heart disease are compensatory changes in cardiac architecture. Recently, we demonstrated that biomechanical signals are central determinants of the nature and severity of the heart’s size and shape. In lieu of this result, our lab seeks to understand how cell and tissue forces are sensed and transduced into changes in cell geometry, differentiation, and proliferation. Given that mechanical forces are more easily manipulated and induce quicker responses than genetic and biochemical strategies, we anticipate this work pioneer new mechanics-based therapeutics that reverse maladaptive cardiac architecture back to normal.