Assistant Professor, Medicine - Endocrinology
Research TopicsHDL structure and function in diabetes and cardiovascular disease and after dietary interventions (saturated fat feeding), weight loss, and pharmacotherapies that alter insulin resistance
Research OverviewCardiovascular disease is the leading cause of death in the US. A significant obstacle in developing drugs to reduce the cardiovascular disease burden is the lack of noninvasive, objective, accurate and sensitive biomarkers. High density lipoprotein (HDL) or good cholesterol is a promising target because low HDL cholesterol is associated with increased cardiovascular risk and because HDL exerts many cardio- and vasoprotective functions. Pharmacotherapy to raise HDL-C has not significantly reduced the cardiovascular burden. Thus, there is a great need for improving our understanding of HDL structure and function. HDL consists of a cholesterol core and a wide array of attached proteins involved in inflammation and blood clot formation. Current clinical guidelines focus on measuring HDL cholesterol (HDL-C) content only.
Our lab is focused on translational studies of HDL attached proteins using mass spectrometry and HDL size and particle numbers by NMR. HDL is isolated by ultracentrifugation from subjects with diabetes and cardiovascular disease, and after the ingestion of a cup of heavy whipping cream (saturated fat). Saturated fat is one mechanism of developing remodeled HDL particles without much change in HDL-C content. We are also interested in studying the effect of insulin resistance (IR), weight loss and pharmacotherapy to ameliorate IR on HDL structure and function. We are pursuing the structural changes in HDL in relation to HDL function studies as cholesterol efflux. The efflux study is a cell culture-based assay where functional HDL particles efficiently remove radioactive cholesterol from the macrophage cell lines and serves as the basis for reverse cholesterol transport where cholesterol is excreted from the body.
Ultimately, measuring HDL structural changes will help us identify subjects at risk of cardiovascular disease, and serve as targets for optimal therapies to reduce the cardiovascular disease burden.