This proposal details a 5-year plan for the development of an academic career in Cardiovascular Medicine. The PI is a trained interventional cardiologist with a PhD, and has recently started his first faculty position at the University of California San Francisco (UCSF), Division of Cardiology. This proposal will utilize the Pi's skills in immunohistochemistry applied to the animal model of myocardial infarction (Ml) already used in the lab of the supervisor, Dr Randall Lee MD, a recognized expert in the application of new therapies for Ml. Additionally, this proposal will permit a dedicated period of time for the PI to learn the techniques and statistical analysis of high throughout microarray analysis. This will be achieved through a collaboration between the Division of Cardiology and the Gladstone Institute of Cardiovascular Disease at UCSF. Apoptosis, also called programmed cell death, of cardiomyocytes following Ml is a crucial aspect of the process of left ventricular remodeling that leads to heart failure. As the population ages and the incidence of heart failure increases, this is becoming and increasingly important clinical problem. Novel strategies to treat apoptosis following Ml are being developed, but are being tested in models of Ml in young animals. We will therefore compare the timescale of apoptosis, as well as the expression of pro- and anti-apoptotic genes, in old versus young animals. A specific inhibitor of caspases, which cause apoptosis in cardiomyocytes, will then be used to see if the anti-apoptotic effects seen in young animals are the same in older animals. This, in turn, will facilitate better planning of anti-apoptotic strategies for clinical trials in older patients. UCSF is an ideal research environment for an aspiring clinician-scientist. The Division of Cardiology and the Gladstone Institute of Cardiovascular Disease are centers of excellence in cardiac research.
Specific aims 1 and 3 can be achieved in the lab of the project supervisor, Dr Lee. The microarray studies will be performed and the data analyzed at the Gladstone Institute under the supervision of Dr Bruce Conklin MD, a pioneer in microarray analysis. Additionally, an advisory committee of esteemed senior researchers will oversee the progress of this project.
|Boyle, Andrew J; Yeghiazarians, Yerem; Shih, Henry et al. (2011) Myocardial production and release of MCP-1 and SDF-1 following myocardial infarction: differences between mice and man. J Transl Med 9:150|
|Boyle, Andrew J; Shih, Henry; Hwang, Joy et al. (2011) Cardiomyopathy of aging in the mammalian heart is characterized by myocardial hypertrophy, fibrosis and a predisposition towards cardiomyocyte apoptosis and autophagy. Exp Gerontol 46:549-59|
|Shih, Henry; Lee, Brian; Lee, Randall J et al. (2011) The aging heart and post-infarction left ventricular remodeling. J Am Coll Cardiol 57:9-17|