Date of Award

9-27-2010

Document Type

Thesis

Degree Name

Medical Doctor (MD)

First Advisor

Alan Dardik MD PhD

Abstract

EphB4, a known venous marker, represents a potential therapeutic target in modern vascular medicine. This study looked at the role of EphB4 as it pertains to basic cell functions in a mouse lung endothelium model (MLEC). Basic science techniques of microscopy, blotting and antibody labeling were used to evaluate and measure cellular response to EphB4 stimulation and manipulation. We found significant changes in MLEC cellular functions due to heterozygous knockout of the EphB4 receptor. These changes included decreased cellular migration and proliferation in knockout cells. We also saw increases in other cellular functions, such as tube formation and nitric oxide formation. From these data we were able to conclude that EphB4 is an active kinase in differentiated cells with a significant inhibitory effect. In EphB4 +/- knockout cell lines there was a lack of EphB4 inhibition and AKT and ERK showed increased activity. This work clearly implicates EphB4 as a major regulator of the basic cellular function of endothelia and highlights the need for further investigation into the specific pathways by which it functions.

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