"Genetic Regulation of Vascular Smooth Muscle Gene Expression" (Mete Civelek, PI) Coronary artery disease is the major cause of death in the United States. Great strides have been made in lowering the number of deaths due to CAD with the advent of lipid-lowering drugs, blood pressure regulating drugs and advanced surgical techniques in the last 30 years. However, still, nearly 800,000 people die from heart disease every year. These patients can benefit from novel therapies that can arise from an in-depth understanding of the disease process. Virtually all the drugs that are currently used for the treatment of coronary artery disease target the risk factors for the disease, such as blood lipids, but not the actual disease process, named atherosclerosis. Dr. Civelek's proposal seeks to identify novel therapeutic targets for atherosclerosis. His team is going to study gene expression as a molecular phenotype in vascular smooth muscle cells which they have isolated from an ethnically diverse population of heart transplant donors. These cells play key roles in the development of hypertension and coronary artery disease. They will construct gene networks that are genetically driven and identify the key nodes of these networks that are relevant to atherosclerosis. This project will lead to the identification of how genetic factors perturb the function of vascular smooth muscle cells. It has three long term goals: (1) to identify functional genetic risk factors that can translate into the clinic for personalized treatments, (2) to identify novel pathways involved in the progression of atherosclerosis, (3) to identify regulators of the pathways perturbed in the disease progression that can be targets for novel drugs. Understanding these biologic networks that underlie the complex interactions in coronary artery disease is required for disease prevention, diagnosis, and treatment. Mete Civelek, PhD, is Assistant Professor of BME and Member of the UVA Center for Public Health Genomics. His new grant is a 3-year $300,000 "Transformational Project Award" from the American Heart Association #19TPA34910021. RELATED:Mete Civelek's new grant from the American Diabetes Association explores genes and diabetes risk