|
Identifying genetic regulators of heart muscle cell formation and heart development holds promise for a greater understanding of congenital heart diseases and therapies for heart failure. Our laboratory studies genes associated with heart diseases and transcriptional regulators that control the commitment of cells to heart muscle cells. Furthermore, we are studying how reactivation of these same regulators cause the failing heart to weaken. Defining mechanisms of gene regulation in the heart will improve our understanding of congestive heart failure, an epidemic with implications for the health and well being of Americans.
My laboratory has a particular interest in identifying genes associated with cardiovascular disease. We perform these studies by comparing gene mutations and polymorphisms in patients with heart disease compared with control subjects without heart disease. These studies are founded on the observation that genetics contribute to common diseases, including hypertension and obesity, as well as congenital heart diseases such as hypertrophic cardiomyopathy, bicuspid aortic valve and aortic aneurysm. To advance these studies we are making use of the recently enriched map of the human genome to identify genes that contribute to human cardiovascular diseases. Once we identify a gene as being associated with cardiovascular disease then we perform molecular and cellular biology studies to better define the mechanism by which that gene may contribute to heart phenotypes and diseases. Research Focus and Highlights Heart muscle cells are unlike any other cell type in the body. During embryonic development heart muscle cells are among the earliest cells to commit themselves to a defined lineage. Importantly, heart muscle cells have distinct origins from skeletal and smooth muscle and they use different gene regulators than other muscle cell types. Shortly after birth the heart completes its developmental program, forming a four-chamber heart with lung and body circulatory systems. Thereafter muscle cells cease to proliferate in any meaningful way, and their response to stress or injury is largely dependent on genetic regulatory mechanisms. Many genetic mechanisms center on specific DNA binding proteins that activate or repress gene expression. These mechanisms are quite complex though, often requiring multiple DNA-binding proteins working in concert to activate a gene. In addition, another group of proteins which physically interact with the DNA-binding proteins can further enhance, or in some cases repress, the activation of genes. Ultimately our goal is to understand the combinatorial aspects of how heart muscle cells activate genes so muscle precursors may be developed. Presently, heart muscle precursors have a limited ability to repopulate a damaged heart. By understanding the genetic mechanisms which define heart muscle cells we may be able to engineer a replacement line of cells to treat damaged hearts.
Research Administrator: Dionne Bradford

|