Area of Doctoral Study: Biochemistry
Undergraduate Institute: University of Texas at El Paso
Graduate Institute: Johns Hopkins University
Research Advisor: Gerald Rosen, Terry Rogers, Ph.D. (UMB)
Description of Research
The focus of my research is to characterize post-transcriptional mechanisms regulating hepatic expression of the low density lipoprotein (LDL) receptor. LDL is the most abundant cholesterol transport vehicle in plasma, and remains a major prognostic indicator of atherosclerotic risk. Hepatic LDL receptors are essential for limiting circulating LDL levels, since cholesterol internalized by the liver can be excreted via conjugation to bile salts. This relationship is clearly seen in familial hypercholesterolemic patients, where depletion or lack of functional LDL receptors dramatically increases circulating LDL, accelerating development of atherosclerosis and associated cardiovascular disease. Elevated plasma cholesterol further impairs hepatic cholesterol excretion because LDL receptor expression is transcriptionally repressed when LDL is abundant. The goal of my thesis research is to identify mechanisms regulating hepatic LDL receptor expression in order to promote the increased uptake and excretion of plasma cholesterol. Our lab has shown in previous studies that protein kinase C (PKC) activation through treatment with phorbol ester, namely phorbol-12-myristate-13-acetate (TPA/PMA), stabilizes the LDL receptor mRNA. I propose to characterize the roles of intracellular signaling pathways on LDL receptor mRNA stability through two specific aims.