Edward P. Feener, Ph.D.
Studies in Dr. Feener’s laboratory are currently aimed at characterizing the role of the plasma kallikrein-kinin system on diabetic vascular complications. A major focus of this work is on the identification of novel mechanisms of action of the plasma kallikrein system on vascular and neuronal tissues. Studies are also underway to further characterize the effects of plasma kallikrein and bradykinin on the pathogenesis of diabetic retinopathy and stroke using animal and cell culture models.
In recent studies, Dr Feener’s laboratory has utilized proteomics to characterize the human vitreous and identify protein changes associated with diabetic retinopathy. Studies initiated by this new proteomics information have revealed a novel role of erythrocyte carbonic anhydrase in the activation of intraocular plasma kallikrein and the induction retinal vascular permeability and retinal edema. The findings have suggested that retinal hemorrhage and impaired blood retinal barrier function may play an active (biochemical) role, mediated in part by plasma kallikrein-stimulated cascades, on diabetic retinopathy progression to diabetic macular edema. Moreover, these studies have also suggested novel potential therapeutic targets for the treatment of this disease, as well as for other retinal conditions that are associated with impaired blood retinal barrier function. Studies are currently investigating the effects of the plasma kallikrein system on retinal cell biology and on retinal physiology in rodent models of diabetes.
Dr Feener’s laboratory is also investigating the effects of diabetes on cerebral hemorrhage and ischemia-induced edema and infarction. Although stroke is a leading cause of death and disability for people with diabetes, the mechanisms that may contribute to the adverse effects of diabetes on the cerebral vasculature remain poorly understood. Studies are ongoing to characterize the role of plasma kallikrein on vascular permeability, edema, and hematoma expansion during stroke in the presence of high blood glucose. Studies are also underway to characterize the role of the plasma kallikrein system on vascular, glial, and neuron damage during stroke in diabetic rodent models.
Liu J, Gao B-B, Clermont AC, Blair P, Chilcote TJ, Sinha S, Flaumenhaft R, Feener EP. Hyperglycemia Induced Cerebral Hematoma Expansion is Mediated by Plasma Kallikrein. Nat Med. 2011 Jan 23. [Epub ahead of print].
Liu J, Gao B-B, Feener EP. Proteomic Identification of Novel Plasma Kallikrein Substrates in the Astrocyte Secretome. Transl. Stroke Res. 2010;1:276-286.
Feener EP. Plasma Kallikrein and Diabetic Macular Edema. Curr Diab Rep. 2010;10(4):270-5.
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 Feb;53(2):175-81
Phipps JA, Feener EP. The kallikrein-kinin system in diabetic retinopathy: Lessons for the kidney. Kidney Int., 2008;73(10):1114-9.
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 Jun;7(6):2516-25.
Gao BB, Clermont A, Rook S, Fonda S, Srinivasan V, Wojtkowski M, Fujimoto JG, Avery RL, Arrigg PG, Bursell S-E, Aiello LP, Feener EP. Extracellular carbonic anhydrase mediates hemorrhagic retinal and cerebral vascular permeability through prekallikrein activation. Nature Medicine. 2007 Feb;13(2):181-8.
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.
Page last updated: September 18, 2014