Research Assistant Professor
Postdoctoral Fellow (1993-1996); Membrane Physiology and Biophysics, Medical College of Pennsylvania, Philadelphia
Department of Pathology & Laboratory Medicine
Member, IME
1070 Vagelos Research Laboratories
3340 Smith Walk
Philadelphia, PA 19104-6383
(215) 573-8161 phone
(215) 573-7227 fax
ilevitan@mail.med.upenn.edu
Education
Ph.D. (1993) Neurobiology, Hebrew University of Jerusalem
Research Interests
Biophysics of ion channels under atherogenic conditions, lipid-protein interactions, coupling of the sub-membrane cytoskeleton to the cell membrane, mechanotransduction
Ion channels are integral membrane proteins that underlie the selective permeability of the membrane to different ions and are responsible for maintaining cell membrane potential and cell volume homeostasis. Impairment of these functions leads to severe cellular dysfunction and cell death. Being some of the most efficient biological molecules, ion channels provide a unique model to study the function of integral membrane proteins on the level of a single molecule. Our research focuses on the impact of two major atherogenic factors on endothelial ion channels: hypercholesterolemia and disturbed blood flow.
Hypercholesterolemia
It is well known that while the healthy endothelium is strongly anti-atherogenic, it looses its anti-atherogenic properties during exposure to high levels of blood cholesterol. Little is known, however, about the mechanisms responsible for the impairment of endothelial function by cholesterol. We have found that an increase in cellular cholesterol impairs the function of the two major types of ion channels in these cells. Furthermore, we have found that chiral isomers of cholesterol have different effects on the two types of endothelial channels giving us the first clue about the mechanism of the interaction between the ion channels and cholesterol. Currently we use a combination of electrophysiology, molecular biology and fluorescence techniques to understand the mechanisms of cholesterol-induced impairment of endothelial ion channels.
Flow environment
Regions of disturbed flow environments, such as regions near arterial bifurcations, branches and bends, are known to be the most susceptible for the formation of atherosclerotic lesions. It has been suggested that the exposure of endothelial cells to disturbed (non-unidirectional) flow environment impairs endothelial function and contributes to the development of atherosclerosis. Mechanosensitive ion channels have been suggested to be the primary mechanotransducers responsible for converting the mechanical signals into a biological response. To study the role of mechanical forces in regulation of endothelial ion channels we have designed a novel parallel-plate flow device that allows electrophysiological recordings to be performed under a well defined flow environment. Our current goal is to determine the role of non-unidirectional flow environment in the regulation of mechanosensitive ion channels in endothelial cells.
Awards, Honors and Memberships in Honorary Societies
1985 DAAD Fellowship, German Academy of Science
1994 Accommodation Award, Annual Meeting of the American Society of Physiology
1994-95 International Postdoctoral Fellowship, American Heart Association
2000 Co-chairperson of the platform session "Anion Channels", Annual Meeting of the Biophysical Society
2002 Co-chairperson of the platform session "Protein-Lipid Interactions", Annual Meeting of the Biophysical Society
2000-04 Scientist Development Award, American Heart Association
Ad Hoc Reviewer:
Journal of Biological Chemistry
American Journal of Physiology
European Biophysical Journal
Cancer Letters
Selected Publications
Levitan, I. and Garber, S.S. Anion competition for a volume-regulated current. Biophysical Journal 75:226-235, 1998.
Levitan, I., Christian, A.E., Tulenko, T.N. and G.H. Rothblat. Membrane cholesterol content modulates activation of volume-regulated anion current (VRAC) in bovine endothelial cells. J. Gen. Physiol. 115:405-410, 2000.
Levitan, I., Helmke, B.P. and P.F. Davies. A chamber to permit invasive manipulation of adherent cells in laminar flow with minimal disturbance of the flow field. Annals of Biomed. Eng. 28:1-10, 2000.
Romanenko V. G., Davies P. F and I. Levitan. Synergistic interactions between osmotic and shear-stress stimuli in the activation of volume-regulated anion current (VRAC) in vascular endothelial cells. American Journal of Physiology. In Press.
Romanenko V. G., Rothblat, G.H. and I. Levitan. Modulation of endothelial inward-rectifier K+ current by optical isomers of cholesterol. Biophysical Journal. In revision.
Sun A. and I. Levitan. Osmotic stress induces re-organization of sub-membrane spectrin cytoskeleton in vascular endothelial cells. Submitted.
Editorials, Reviews, Chapters:
Levitan, I. and S.S. Garber (1997). Volume Regulated Anion Current and Cytoskeleton Interaction. "From Ion Channels to Cell-to-Cell Conversations." R. Latorre and J.C. Saez, editors. Plenum Press, 1997 pp.245-265.
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