Edward P. Feener, Ph.D.
Dr. Feener is an Investigator in the Section on Vascular Cell Biology and Director of the Proteomics Core at Joslin and an Assistant Professor of Medicine at Harvard Medical School. He received his doctoral degree in Biochemistry from Boston University and postdoctoral training in the Section on Cellular and Molecular Physiology at Joslin. He is a past recipient of a Mary K. Iacocca Fellowship and FIRST Award from the National Institutes of Health.
The laboratory of Dr. Feener studies the cardiovascular and microvascular complications of diabetes, focusing on angiotensin II (A-II) signal transduction and action in blood-vessel cells and tissues. A-II is a hormone that regulates blood pressure and a variety of vascular cell functions. Increased A-II action in diabetes has been implicated in cardiovascular disease, diabetic nephropathy (kidney disease) and diabetic retinopathy (eye disease). The A-II system has emerged as a major therapeutic target for preventing diabetic complications. For example, treating diabetes with angiotensin inhibitors can slow the rate of developing kidney disease and heart disease. Further understanding of the adverse effects of A-II on blood vessels could reveal new information on the underlying mechanisms that contribute to diabetic vascular complications.
Dr. Feener demonstrated that A-II stimulates the expression of plasminogen activator inhibitor-1 (PAI-1)a protein that stabilizes blood clots and inhibits protein-degrading enzymes in blood-vessel walls. In addition, his lab has shown that A-II inhibits insulin signaling and regulates retinal blood flow. These findings have revealed new mechanisms of actions of the A-II system on blood vessels and has expanded understanding of the effects of drugs designed to inhibit the actions of the A-II system#drugs such as angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers.
The effects of A-II are mediated by the activation of particular receptors on vascular cells that are linked to a variety of messenger systems and signaling pathways. Dr. Feener’s laboratory is now probing deeper into the intracellular signals generated by A-II receptors. These studies seek to identify the biochemical mechanisms by which A-II contributes to endothelial dysfunction and vascular inflammation in diabetes.
Another ongoing area of investigation focuses on the identification of vascular protein abnormalities in diabetes. This project uses proteomics mass spectroscopy (a high-speed protein analysis technology) and bioinformatics to identify abnormalities in the diabetic heart and retina. These studies will provide new molecular information about the role of the angiotensin system in the pathogenesis of diabetic cardiovascular disease and retinopathy and could reveal novel therapeutic targets for diabetic vascular complications.
Upcoming research in Dr. Feener’s laboratory will investigate how diabetes affects A-II’s pro-inflammatory and pro-fibrotic actions. Dr. Feener and his colleagues will also expand the use of proteomics mass spectroscopy to improve the detection of proteins expressed at low levels and the identification of protein modifications. This work will enable the Feener laboratory to further define the A-II signaling mechanisms and actions in diabetes. It also may provide a panel of protein targets to evaluate the effectiveness of treatments aimed at preventing early abnormalities in the vasculature of patients with diabetes.
Selected References
Gao B, Hansen H, Chen HC, Feener EP. Angiotensin II stimulates phosphorylation of an ectodomain-truncated platelet-derived growth factor receptor b and its recruitment to class IA PI3-kinase in vascular smooth muscle cells. Biochem J 397:337-344, 2006.
He Z, Way KJ, Arikawa E, Chou E, Opland DM, Clermont A, Isshiki K, Ma RC, Scott JA, Schoen FJ, Feener EP, King GL. Differential regulation of angiotensin II-induced expression of connective tissue growth factor by protein kinase C isoforms in the myocardium. J Biol Chem 280:15719-15726, 2005
Feener EP, Rosario F, Dunn SL, Stancheva Z, Myers, MG-Jr. Tyrosine phosphorylation of Jak2 in the JH2 domain inhibits cytokine signaling. Mol Cell Biol 24:4968-4978, 2004.
Chen HC, Feener EP. MEK1,2 response element mediates angiotensin II-stimulated plasminogen activator inhibitor-1 promoter activation. Blood 103:2636-2644, 2004.
Horio N, Clermont AC, Abiko A, Abiko T, Shoelson BD, Bursell SE, Feener EP. Angiotensin AT1 receptor antagonism normalizes retinal blood flow and acetylcholine-induced vasodiliation in normotensive diabetic rats. Diabetologia 47:113-123, 2004.
