Overview

An increased level of low-density lipoprotein (LDL) cholesterol, the so-called “bad cholesterol”, in the circulation is a primary risk factor for the development of cardiovascular heart disease. Our lab’s primary research interests are cellular and molecular mechanisms that regulate cholesterol homeostasis in the body and ultimately blood LDL-cholesterol levels.

Clearance of LDL from the circulation requires the LDL receptor, a protein on the cell surface that binds to LDL particles with high affinity and mediates their uptake into cells, mainly in the liver. Since the liver is the primary means for LDL clearance, increased liver LDLR protein expression is a highly desirable goal for therapies aimed at lowering cardiovascular disease risk.

Indeed, the efficacy of the widely prescribed statin drugs is ascribed to their ability to increase liver LDL receptors at the gene transcriptional level. However, many patients undergoing statin therapy do not reach therapeutic goals for cholesterol lowering or suffer unacceptable secondary effects, highlighting the need for improved and/or alternate means for increasing liver LDL receptor function.