Edward A. Fisher, MD, PhD

Medicine (Cardiology) – Steering Committee, Primary Mentor

Dr. Fisher’s laboratory focuses on the cell biology of hepatic lipid and lipoprotein metabolism and the regression of atherosclerosis. Dr. Fisher’s laboratory was the first to show that this degradation is mediated by the ubiquitin-proteasome pathway and the cytosolic chaperone, Hsp70. His lab has also been the first to demonstrate a non-proteasomal pathway of apoB degradation regulated by dietary fatty acids, a process that may also be regulated by insulin. Importantly, this non-proteasomal pathway may be dysregulated in insulin-resistance (such as seen in patients with type II diabetes or obesity) and, thereby, contribute to the over-production of atherogenic lipoproteins that increase the risk of coronary artery disease in these metabolic states. His laboratory is using cell and molecular biological approaches on experimental models as diverse as cell-free systems and tissue-specific knockout mice. In addition, his laboratory investigates the enzymes in the liver responsible for the esterification and hydrolysis of cholesteryl esters. Dr. Fisher’s laboratory is also interested in the molecular factors that regulate the progression and regression of atherosclerotic plaques, as well as the development of novel plaque imaging agents. This research relies on mouse models of atherosclerosis and current projects focus on: the regression of plaques after the normalization of hyperlipidemia; the effects of HDL on plaque progression and regression; the lipid-independent role of apoE on neointima formation after arterial injury; the effects of hyperglycemia and insulin-resistance as separate factors on atherosclerosis progression and regression; and the mechanisms by which HDL can deliver imaging agents to plaques for their non-invasive assessment.