Objective The brain vasculature has evolved to protect the central nervous system from the constantly changing milieu in the blood stream. Endothelial cells of brain capillaries form the so called blood brain barrier (BBB), an active permeability barrier and transport system which allows a selective passage of nutrients from blood to the nervous tissue. The continuous cross talk of endothelial cells, pericytes and nervous cells influences many vascular functions and determines and maintains the BBB characteristics after birth. Our limited knowledge of the nature of these signals prevents effective therapy of several diseases such as hemorrhagic stroke or brain edema. Furthermore, the development of tools to reversibly ¿open¿ the barrier would strongly improve drug delivery to the brain.In the present project we propose to tackle the problem by studying the transcriptional mechanisms which direct BBB differentiation. This strategy is based on preliminary work which shows that the cross talk between nervous cells and the endothelium is mediated by Wnt factors and downstream beta-catenin transcriptional activity. The understanding of the mechanism of action of Wnt signaling on brain endothelium may yield novel strategies and tools for modulating BBB permeability.The project is divided in three related objectives: 1) to define the mechanism of action and downstream partners of Wnt in brain angiogenesis and BBB differentiation; 2) to use this knowledge to develop an optimized BBB model in vitro and in vivo; 3) to test whether modulation of Wnt signaling may have a therapeutic impact in the regulation of BBB in pathological conditions. Fields of science natural sciencesbiological sciencesneurobiologymedical and health sciencesbasic medicineneurologystroke Programme(s) FP7-IDEAS-ERC - Specific programme: "Ideas" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Topic(s) ERC-AG-LS4 - ERC Advanced Grant - Physiology, Pathophysiology and Endocrinology Call for proposal ERC-2010-AdG_20100317 See other projects for this call Funding Scheme ERC-AG - ERC Advanced Grant Host institution IFOM-ISTITUTO FONDAZIONE DI ONCOLOGIA MOLECOLARE ETS EU contribution € 2 390 200,00 Address VIA ADAMELLO 16 20139 Milano Italy See on map Region Nord-Ovest Lombardia Milano Activity type Research Organisations Principal investigator Elisabetta Dejana (Prof.) Administrative Contact Carlo Raimondi Cominesi (Mr.) Links Contact the organisation Opens in new window Website Opens in new window Total cost No data Beneficiaries (1) Sort alphabetically Sort by EU Contribution Expand all Collapse all IFOM-ISTITUTO FONDAZIONE DI ONCOLOGIA MOLECOLARE ETS Italy EU contribution € 2 390 200,00 Address VIA ADAMELLO 16 20139 Milano See on map Region Nord-Ovest Lombardia Milano Activity type Research Organisations Principal investigator Elisabetta Dejana (Prof.) Administrative Contact Carlo Raimondi Cominesi (Mr.) Links Contact the organisation Opens in new window Website Opens in new window Total cost No data
