Objective
Cerebral cavernous malformations (CCM) is a disease characterized by focal capillary-venous cavernomas located in the central nervous system. These malformations are fragile and bleed leading to seizures, paralysis and cerebral hemorrhages. The familial form of CCM is due to loss of function mutations of anyone of three genes called Ccm1, Ccm 2 and Ccm 3. Open skull surgery is the only possible therapy since effective medical treatments are still missing. In mouse models of CCM and human patients’ specimens, endothelial cells (ECs) lining the cavernomas co-express endothelial, mesenchymal and stem cell markers. These features combined to high cell proliferation are reminiscent of tumor initiating cells. In preliminary work, we isolated a rare population of highly proliferative ECs (V-EPC) intermingled with the normal vascular endothelium in vivo and co-expressing endothelial and stem cell markers. Our working hypothesis is that CCM originates from the clonal expansion of these V-EPCs that are more sensitive than mature endothelium to inactivation of Ccm genes. This possibility is supported by the observation that V-EPCs present a comparable gene expression profile and selective markers than the ECs lining CCM cavernomas. The project is divided in three related objectives: 1) To define the nature and functions of V-EPCs in normal vessels; 2) to test the capacity of V-EPCs to trigger the formation of CCM by undergoing clonal expansion in vivo; 3) to test whether targeting V-EPCs or inducing V-EPC maturation by pharmacological tools reduce or prevent the formation of CCM. If successful this work will introduce novel concepts in vascular biology such as: 1) the presence of resident V-EPCs that are differentially sensitive than mature endothelium to the same genetic mutation and angiogenic stimuli; 2) the identification of specific signaling pathways in V-EPC that explain their high proliferative potential; 3) the identification of V-EPC as therapeutic targets for CCM.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.
- medical and health sciences medical biotechnology cells technologies stem cells
- natural sciences biological sciences genetics mutation
- medical and health sciences clinical medicine angiology vascular diseases cerebrovascular diseases
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Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC)
MAIN PROGRAMME
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Topic(s)
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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.
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.
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-ADG - Advanced Grant
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Call for proposal
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) ERC-2016-ADG
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Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.
20139 Milano
Italy
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.