Objective
Colorectal cancer (CRC) is the third most commonly diagnosed cancer in both men and women worldwide. Although some CRCs are effectively treated through the standard strategy of surgery, radiation and/or chemotherapy, some patients have a recurrence of their cancer and a spread to other parts of the body that threatens life. Despite decades of research, we are unable to predict which cancers will be effectively treated and which are likely to spread. In support of the well-documented resistance of cancer stem cells (CSCs) to conventional therapies high stem cell (SC) signature scores statistically associate with a high risk of tumor relapse in patients. Targeting CSCs thus constitute a determinant medical issue and identify novel players of SC plasticity is a prerequisite to open novel therapeutic avenues. Using ex vivo organoid cultures, we recently demonstrated that thyroid hormones (THs) reduce the pool of intestinal SCs by triggering premature cell differentiation. Even if the underlying mechanisms remain elusive, our preliminary results tend to demonstrate that the TH-induced loss of stemness relies on a profound modification of the ratio between TRα1 and TRβ1 (TRs), with deep consequences on the expression of WNT and NOTCH downstream target genes. My proposal will pave the way for a unique focal area in the field of CSCs. Combining original approaches such as ex vivo 3D human colosphere and organoid cultures, in vivo CSC tracing experiments as well as innovative proteome mapping techniques (BioID and APEX2) I aim to address the potential interest of disrupting the THs/TRs balance in order to enforce CSC differentiation with the final aim to eradicate them by conventional therapies. Furthermore and more importantly, by minoring CSC plasticity, it will strongly reduce their adaptability to stress conditions and limit escape mechanisms.
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.
- natural sciences biological sciences biochemistry biomolecules proteins proteomics
- medical and health sciences clinical medicine surgery
- medical and health sciences medical biotechnology cells technologies stem cells
- medical and health sciences clinical medicine oncology colorectal cancer
- natural sciences mathematics pure mathematics mathematical analysis functional analysis
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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.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions
MAIN PROGRAMME
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H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility
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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.
MSCA-IF-EF-RI - RI – Reintegration panel
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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) H2020-MSCA-IF-2018
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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.
75794 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.