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Content archived on 2024-05-30

Transcriptional regulation of endothelial blood brain barrier differentiation by Wnt signaling

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 (EuroSciVoc)

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Topic(s)

Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.

Call for proposal

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ERC-2010-AdG_20100317
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Funding Scheme

Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.

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

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Region
Nord-Ovest Lombardia Milano
Activity type
Research Organisations
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Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

No data

Beneficiaries (1)

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