Request for Funding

Medical Student Research Fellowship for Summer 2001

Mentor: Fiemu E. Nwariaku MD

Department: Surgery

Room number: E6.218

Mail Code: 9156

Phone number: 214-648 9968

E-mail: fiemu.nwariaku@UTSouthwestern.ed

Project title: The Role of Cadherin 5 in the Regulation of Endothelial Permeability

Human subjects IRB approved project number (where applicable):

Animal subjects IRB approved project number (where applicable):

Project Type (patient-based research, animal-based research, or basic research; this characterization is only to permit a general classification for grouping similar types of projects)

Basic research

Brief Description of Project:

Edema formation is a major component of the Systemic Inflammatory Response Syndrome (SIRS)and Acute Respiratory Distress Syndrome(ARDS). The ability to modulate vascular endothelial barrier function and prevent extravasation of fluid, proteins and inflammatory cells would be invaluable in treatment.). Despite the abundance of studies describing TNF-a -induced increased endothelial permeability, the mechanisms by which TNF-a causes increased endothelial permeability is unknown. Our central hypothesis is that TNF-alpha increases vascular endothelial permeability by mitogen-activated protein kinase (MAPK) dependent reduction of vascular endothelial cadherin (VE cadherin, cadherin 5). Vascular endothelial cadherin is an endothelial-specific protein expressed at the intercellular contacts of confluent vascular endothelial cells which maintains endothelial cell adhesion and endothelial monolayer integrity. Our project will relate TNF-alpha-induced vascular endothelial permeability and MAP Kinase activation to changes in VE cadherin expression. Our strategy is to assess VE cadherin distribution on human umbilical vein endothelial cells morphologically by immunofluorescence laser confocal microscopy and to quantify VE cadherin protein by Western immunoblot after exposure to TNF-alpha. We propose to measure endothelial monolayer permeability by two methods; (1) Measuring the amount of biotin-labeled bovine serum albumin (BSA) crossing the endothelial monolayer, and (2) Trans-endothelial electrical resistance of human umbilical vein endothelial monolayers.

Previous Research Activities or Publications with Medical Students:

Andy Adusei, August 2000

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