INDIVIDUAL RESEARCHER
Peter A. Vincent
, Ph.D.
Professor
and Associate Director
e-mail: vincenp@mail.amc.edu
Education
1988 - Ph.D. from Dept. of Physiology, Albany Medical CollegeCurrent Research
Endothelial cells line the inner walls of blood vessels where they play an active role in controlling many physiological functions of the vasculature. One such function of the endothelium is regulating the flux of proteins and fluid from the vascular space into the interstitium. Under normal conditions endothelial cells are tightly connected to one another by proteins on adjacent cells and there is very little flux of protein through the spaces between these cells. However, a number of pathological states, such as hypertension or inflammation, have been shown to be associated with increased flux of protein across the endothelium. Such as increases in the paracellular flux of protein have been implicated in the initiation of vascular diseases such atherosclerosis or vascular remodeling during systemic and/or pulmonary hypertension. Adherens junctions are a major type of cell-cell junction that contributes to the maintenance of endothelial monolayer integrity. Adherens junctions are formed by transmembrane proteins called cadherins that bind in a homophilic fashion to connect one endothelial cell to another. The cytoplasmic portion of cadherins are connected to the actin cytoskeleton by a complex network of proteins. The research in this lab focuses on how the cadherins and proteins in the adherens junction are involved in controlling the paracellular flux of proteins across the vascular endothelium. Transforming growth factor ß (TGFß) is a cytokine which has been shown to alter endothelial cell morphology resulting in an increased flux of proteins across the endothelial cell barrier. Current investigations are underway to determine the role of adherens junction disassembly in the signal transduction pathway that leads to TGFß induced decreases in endothelial monolayer integrity. Models are also being pursued to utilize molecular biology techniques in vitro using monolayers of isolated endothelial cells and in intact organs using isolated perfused rat lungs to determine the role of the adherens junction in the maintenance of endothelial monolayer integrity.References
- Clements RT, Minnear FL, Singer HA, Keller RS, Vincent PA. RhoA and Rho-kinase dependent and independent signals mediate TGF-beta-induced pulmonary endothelial cytoskeletal reorganization and permeability. Am J Physiol Lung Cell Mol Physiol. 2005 Feb;288(2):L294-306.
- Vincent PA, Xiao K, Buckley KM, Kowalczyk AP. VE-cadherin: adhesion at arm's length. Am J Physiol Cell Physiol. 286(5):C987-97, 2004.
- Iyer S, Ferreri DM, DeCocco NC, Minnear FL, Vincent PA. VE-Cadherin-p120 Interaction is required for maintenance of endothelial barrier function. Am J Physiol Lung Cell Mol Physiol. 286(6):L1143-53, 2004.
- Mehta D. p120: the Guardian of Endothelial Juntional Integrity. Am J Physiol 286:1140-1142, 2004.