Date of Award
Doctor of Philosophy (PhD)
Heart related deaths are the number one cause of death in the United States. While heart failure and other mechanical issues are common, arrhythmias account for the majority of these deaths. By understanding the genetic architecture that patterns the normal cardiac conduction system, we can further deepen our understanding of how arrhythmias arise and develop targeted therapies to treat this deadly class of disease. I have found that canonical Wnt signaling is necessary for development of the atrioventricular junction. Furthermore, absence of myocardial Wnt signaling leads to tricuspid atresia. Overexpression of Wnt signaling leads to development of ectopic atrioventricular junction tissue and induces delayed conduction velocity and other electrophysiological properties of nodal tissue. I have further found that Wnt signaling is downregulated by Notch signaling and this downregulation is required for Notch induced ventricular preexcitation. I have also developed a gene therapy platform for testing the role of these genes in cultured mouse and human cardiac tissue.
Chair and Committee
David Ornitz, Jeanne Nerbonne, Donald Elbert, Robert Mecham, Jim Skeath,
Gillers, Benjamin S., "Programming the Myocardium: the Notch-Wnt Axis" (2015). Arts & Sciences Electronic Theses and Dissertations. 526.