Objective
With this project I propose to identify fundamental mechanisms of cardiovascular calcification (CVC) and new therapeutic targets using zebrafish as a model system.
CVC, characterised by progressive calcification of the soft tissue causing impaired blood circulation, is a frequent form of cardiovascular disease. Because the pathophysiology of CVC is highly heterogeneous, the exact cell types and signalling pathways triggering tissue calcification are still unknown, thus limiting therapy options. Most studies on CVC rely on in vitro systems, which fail to reproduce the multicellular environment, or mammalian in vivo models, limited for live-imaging and high-throughput analyses.
By combining my expertise in cardiovascular research and bone biology, I propose to use zebrafish as a model to elucidate the multifactorial mechanisms of CVC, focusing on different developmental stages and cardiovascular tissues. In Aim 1, I will use a broad array of zebrafish genetic models to characterise the cellular dynamics, molecular mechanisms and functional impact of CVC in vivo. I will also study the role of specific cell populations present in regenerating valves and human valve implants with CVC. In Aim 2, I propose to identify new local and systemic therapeutic strategies to block/reverse CVC, taking advantage of the zebrafish amenability for genetic manipulation and high-throughput screening. I will recruit bone-degrading cells to the CVC site and determine their potential to reverse tissue calcification. Moreover, I will select a short list of small molecules identified in a large-scale screen in zebrafish and will test their therapeutic potential in cardiovascular cells derived from hiPSCs of CVC patients.
Altogether, with this interdisciplinary approach, I expect to bring a new perspective on the mechanisms and therapeutic targets to block/reverse CVC, which could have a considerable impact on the European population, severely affected by these diseases.
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: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- medical and health sciences basic medicine physiology pathophysiology
- natural sciences biological sciences molecular biology
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Keywords
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
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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HORIZON.1.1 - European Research Council (ERC)
MAIN PROGRAMME
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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.
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.
HORIZON-ERC - HORIZON ERC Grants
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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-2021-STG
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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.
75654 PARIS
France
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.