Bernstein Lab

Our research program focuses on regulation of cardiovascular function in both normal physiologic states as well as in disease states such as cardiomyopathy. Current studies are focused on elucidating the role of alpha and beta-adrenergic receptors in regulating cardiovascular function and in mediating cardioprotection and cardiotoxicity. Utilizing murine gene targeting techniques, our lab was among the first to stu G protein coupled receptor signaling in the intact animal.  We developed and verified many of the now-standard techniques of physiologic assessment of transgenic models of cardiovascular disease, and demonstrated the value of chronic instrumentation as well as exercise studies to monitor murine cardiovascular function.

One major focus of our studies is the role of different ß-receptor subtypes in the pathogenesis of cardiomyopathy. Utilizing models of both toxic (catecholamine and adriamycin) and genetic (MLP) cardiomyopathy, we have demonstrated that in some conditions, ß1-receptors mediate pathways of cardiotoxicity whereas ß2-receptors mediate pathways of cardioprotection. In other conditions, this role is reversed. These diverse roles appear to be regulated by differential cross-talk with protein kinase C isozymes and differential stimulation of MAP kinases, as well as differential patterns of gene expression as determined by microarray analysis. Ongoing studies are examining crosstalk between ß-receptors and mitochondrial stress pathways and intracellular calcium transients.

Another major focus is the difference in response of the left and right ventrciles to cardiovascular stress. We are interested in studying the "vulnerable right ventricle," common in patients with cyanotic congenital heart disease. We are studying differential gene expression in models of left vs. right ventricular hypertrophy, models of pulmonary stenosis and insufficiency, and differences in intracellular calcium signaling between right and left ventricles.

Posters (Powerpoint) and Abstracts (pdf) From Recent National Presentations