Grant: Operating Grant

The cells that line the interior of the heart and blood vessels are called endothelial cells. These cells are necessary for the heart to form key structures that divide the heart into four chambers, such as the heart valves. Heart defects are the most common congenital anomaly seen in newborns, and heart valve surgery is the commonest type of heart surgery performed in the adult. A key process in the formation of the heart valves and the walls that divide the four chambers of the heart is the formation and differentiation of embryonic tissue (called cardiac cushion), which partitions the heart into atria and ventricles, and a left and a right side. During this process the endothelial cells that line the interior of the heart change into a different type of cell that support the heart valves. This process is called endothelial-to-mesenchymal transdifferentiation (EMT). At the same time during development of an embryo, a specialized subset of endothelial cells lining the large blood vessel exiting the heart called the aorta change into cells that eventually form the blood that circulates in our body. This process is called endothelial-to-hematopoietic (blood cell) transdifferentiation (EHT). This grant is designed to identify the gene networks that are responsible for transforming the same cell type into different types of cells. In particular, we are attempting to gain a deeper understanding of how heart valves develop. We hope that a better understanding of these processes will provide direction for genetic diagnosis, prevention, and potentially tissue engineering efforts to create artificial heart valves.