Transcriptional regulation of endothelial blood brain barrier differentiation by Wnt signaling

Objetivo

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.

Ámbito científico

Régimen de financiación

ERC-AG - ERC Advanced Grant

Institución de acogida

IFOM-ISTITUTO FONDAZIONE DI ONCOLOGIA MOLECOLARE ETS

Aportación de la UE

€ 2 390 200,00

Dirección

VIA ADAMELLO 16
20139 Milano
Italia

Región

Nord-Ovest Lombardia Milano

Tipo de actividad

Research Organisations

Investigador principal

Elisabetta Dejana (Prof.)

Contacto administrativo

Carlo Raimondi Cominesi (Mr.)

Enlaces

Contactar con la organización Sitio web

Coste total

Sin datos

Beneficiarios (1)