Cardiac repair and regeneration

The heart is unable to regenerate heart muscle after a heart attack and lost cardiac muscle is replaced by scar tissue. Scar tissue does not contribute to cardiac contractile force and the remaining viable cardiac muscle is thus subject to a greater hemodynamic burden. Over time, the heart muscle eventually fails leading to the development of heart failure and 500,000 patients are diagnosed annually in the United States with heart failure. Thus the inability of the heart to regenerate cardiac muscle, coupled with a predominant fibrotic injury response remain major fundamental obstacles to treating heart disease.

Our laboratory studies the interface of cardiac fibroblasts (scar forming cells) and cardiac progenitors in determining how a cross talk between these cells regulates cardiac repair. We use murine models of cardiac injury and use a variety of fate mapping and conditional knockout strategies to alter specific genes at specific time points after injury to investigate our questions. Using transgenic and conditional knock out strategies, we aim to alter the fibrotic repair response of the heart to enable regeneration.

The scar response is broadly conserved across different organs. For instance the temporal pattern of activation of inflammatory cells and scar forming cells in the heart atre brain are remarkable similar. Thus understanding and being able to treat fibrosis in one organ may enbale us to apply the same therapeutic principles across multiple organs. 

Scar tissue is no longer considered dead tissue but a living microenvironment within an organ. Scars persist in the heart and brain long after the inciting stimulus has abated. Yet mechanisms of scar persistence are ill understood. using fate mapping and protein turnover messurement tools, we are starting to investigate the biology of chronic scars.