Objectif 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. Champ scientifique 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) Thème(s) ERC-AG-LS4 - ERC Advanced Grant - Physiology, Pathophysiology and Endocrinology Appel à propositions ERC-2010-AdG_20100317 Voir d’autres projets de cet appel Régime de financement ERC-AG - ERC Advanced Grant Institution d’accueil IFOM-ISTITUTO FONDAZIONE DI ONCOLOGIA MOLECOLARE ETS Contribution de l’UE € 2 390 200,00 Adresse VIA ADAMELLO 16 20139 Milano Italie Voir sur la carte Région Nord-Ovest Lombardia Milano Type d’activité Research Organisations Chercheur principal Elisabetta Dejana (Prof.) Contact administratif Carlo Raimondi Cominesi (Mr.) Liens Contacter l’organisation Opens in new window Site web Opens in new window Coût total Aucune donnée Bénéficiaires (1) Trier par ordre alphabétique Trier par contribution de l’UE Tout développer Tout réduire IFOM-ISTITUTO FONDAZIONE DI ONCOLOGIA MOLECOLARE ETS Italie Contribution de l’UE € 2 390 200,00 Adresse VIA ADAMELLO 16 20139 Milano Voir sur la carte Région Nord-Ovest Lombardia Milano Type d’activité Research Organisations Chercheur principal Elisabetta Dejana (Prof.) Contact administratif Carlo Raimondi Cominesi (Mr.) Liens Contacter l’organisation Opens in new window Site web Opens in new window Coût total Aucune donnée