Grant: Project Grant

The major goal of this study is to understand why rising level of cholesterol in our bodies causes cardiovascular diseases, the number one leading cause of deaths around the world. This phenomenon is called hypercholesterolemia, which causes abnormally high levels of cholesterol in the blood. Individuals with this symptom are more likely to develop fatty plaques on the blood vessels, a disease called atherosclerosis and a major cause of stroke and heart attack. Our research will investigate how cholesterol and other lipids are moved in and out of cells by protein machineries in cell membranes, a key element to understanding how lipids accumulate in the body. Specifically, this research proposal will focus on a group of lipid trafficking proteins called ABC transporters, which use ATP (the primary energy currency in all living beings) and eliminate cholesterol and lipids from building-up in our bodies. Without these pumps, cholesterol and lipids can build up, leading to atherosclerosis, stroke, obesity, and dementia. With our research, we will learn how this type of protein move lipids out of the cell by building molecular models and analyzing the molecular details underlying their lipid- pumping function. These models will enable logical design of next-generation drugs, which will better control cholesterol to treat hypercholesterolemia and its related cardiovascular diseases. By pinpointing the interactions between these proteins and their working partners, cholesterol transport activity can serve as a new biomarker to allow a better and more precise diagnosis for affected patients.