Affiliate Faculty, Biochemistry and Biophysics
Ph.D. 1993, University of Pennsylvania
KEYWORDS: Signal Transduction Mechanisms; G Proteins; CNS and Autonomic Pharmacology
The initial intracellular response to many external stimuli, including hormones, growth factors, and neurotransmitters, involves activation of a membrane phospholipid-hydrolyzing enzyme, phospholipase C-β (PLC-β) whose product second messengers mobilize intracellular calcium and activate protein kinase C (PKC) leading to a wide variety of cellular responses. Among these responses are normal processes such as smooth muscle (e.g. blood vessel) contraction, neurotransmitter release and stimulation of cell growth. However, too much PLC-β signaling correlates with enlarged atria in mice and humans with heart valve disease and atrial fibrillation. Too little PLC-β seems to predispose cells to malignancies including leukemia, lymphoma and skin tumors. We are seeking to understand the means by which PLC-β activity is regulated intracellularly in normal and disease states as a means of identifying new targets for therapeutic agents. To this end, my laboratory utilizes biochemical, molecular biology, and cell biology techniques to study PLC-β function and regulation.