Human congenital heart disease, the most common form of heart disease in childhood, occurs in about 1% of live births and up to 10% of stillbirths. Presently, the most effective therapy for cardiac diseases is heart transplantation. However, due to the shortage of organs, cost and inaccessibility of treatment for most affected individuals this remains a limited therapeutic option. Alternative treatment is the administration of drugs that improve myocardial contractility, though this treatment is only effective as a short term therapy, with the 5-year survival rate using current agents being less than 60%. An alternative therapeutic option is to treat patients with cardiac progenitor cell populations that could infiltrate and repair damaged heart tissue. Thus, the ability to isolate and propagate cell populations that can differentiate into cardiomyocytes in vivo offers the opportunity to treat a wide range of cardiac diseases. To this end, our lab is interested in understanding the relationship between cardiac progenitor proliferation and the onset of cardiac differentiation focusing on the endogenous roles of the transcription factors TBX5 and CST and the protein phosphatase SHP-2.