Project Details
Projekt
Identification of VEGF-induced signaling events involved in angiogenesis and vascular permeability
Applicant
Professor Matthias Clauss, Ph.D.
Subject Area
Pathology
Term
from 2001 to 2004
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 5348612
In previous studies we have identified vascular endothelial growth factor (VEGF)-receptor specific VEGF-homologues and mechanisms which can distinguish angiogenic activities from vascular permeability activities of VEGF. Here we intend to elucidate signaling events evoked by VEGF, which regulate endothelial sprout formation and angiogenesis in the CAM-assay. For this purpose we will employ mainly chemical inhibitors specific for individual signaling molecules but also adenoviral gene transfer. We will analyze the role of the identified regulatory molecules in individual steps of sprouting angiogenesis such as migration of endothelial cells or activation of proteases. Furthermore, we will test the significance of the identified signaling steps in additional models of angiogenesis, which are tumor angiogenesis and collateral growth in the model of femoral artery occlusion. Finally, we plan to analyze these molecules for their interference with VEGF to induce vascular permeability. In particular, we will test the hypothesis that the p38 MAP-kinase is a molecular switch that can be used to separate angiogenesis from vascular permeability. The overall goal of this study is to develop new tools and strategies for anti-angiogenic therapy and therapeutic angiogenesis and to separate from side effects such as vascular permeability.
DFG Programme
Priority Programmes
