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Investigator Specifics:
Professional Details:
Publications
CV

Member of Section:
Vascular Cell Biology

Core Director:

Proteomics Core

Current Fellows, Students, or Lab Members:
Benbo Gao
Jia Liu, Ph.D
Yan Tan, M.D.
Gongxiong Wu, M.D., Ph. D.

Past Fellows, etc.:
Hong-Chi Chen
Lisa Stuart


 
 
Edward P. Feener, PhD
Investigator
Joslin Diabetes Center
Associate Professor of Medicine
Harvard Medical School
 
7/17/1989 -  
 
 Vascular Complications in Diabetes

The laboratory of Ed 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, it is known that 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 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 signaling signals generated by A-II receptors. These studies seek to identify the biochemical mechanisms by which A-II contributes endothelium 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 brain and retina. These studies will provide new molecular information about the pathogenesis of stroke and diabetic retinopathy in people with diabetes and could reveal novel therapeutic targets for diabetic vascular complications.


Biographical Sketch

Dr. Feener is an Investigator in the Section on Vascular Cell Biology and Director of the Proteomics Core at Joslin and an Associate 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 (NIH).


Selected References

Phipps JA, Clermont AC, Sinha S, Chilcote TJ, Bursell S-E, Feener EP. Plasma kallikrein mediates angiotensin AT1 receptor stimulated retinal vascular permeability. Hypertension 2009 Jan 5. [Epub ahead of print]

Gao BB, Stuart L, Feener EP. Label-free quantitative analysis of 1D-PAGE LC/MS/MS proteome: Application on angiotensin II stimulated smooth muscle cells secretome. Mol Cell Prot. 2008 Dec;7(12):2399-409. Epub 2008 Aug 2.

Gao BB, Chen X, Timothy N, Aiello LP, Feener EP. Characterization of the vitreous proteome in diabetes without diabetic retinopathy and diabetes with proliferative diabetic retinopathy. J Proteome Res 2008 2008 Jun;7(6):2516-25.

Phipps JA, Feener EP. The kallikrein-kinin system in diabetic retinopathy: Lessons for the kidney. Kidney Int., 2008 2008 May;73(10):1114-9.

Gao B, Clermont A, Rook S, Fonda SJ, Srinivasan V, Wojtkowski MD, Fujimoto JG, Avery RL, Arrigg PG, Bursell SE, Aiello LP, Feener EP. Extracellular carbonic anhydrase mediates hemorrhagic retinal and cerebral edema through prekallikrein activation. Nature Medicine 2007;13(2):181-8.

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 2006.

Chen H-C, Feener EP. MEK1,2 response element mediates angiotensin II-stimulated plasminogen activator inhibitor-1 promoter activation. Blood 103:2636-2644, 2004.

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. 2004 24:4968-4978.

Horio N, Clermont AC, Abiko A, Abiko T, Shoelson BD, Bursell S-E, Feener EP. Angiotensin AT1 receptor antagonism normalizes retinal blood flow and acetylcholine-induced vasodiliation in normotensive diabetic rats. Diabetologia 47:113-123, 2004.