Objective
Recent large-scale genomic profiling studies have uncovered mutations in the SWI/SNF (SWItch / Sucrose Non-Fermentable) chromatin remodelling complex subunits in 20% of solid tumours. Most of these tumours resist to current therapies. To address this highly unmet medical need, it is crucial to determine how to harness vulnerabilities induced by SWI/SNF defects. Recent evidence shows that SWI/SNF influences the DNA damage response and is involved in shaping tumour immunogenicity. Though, whether there is a link between these observations, and whether the latter may be therapeutically exploited is unknown. Further, the impact of SWI/SNF defects on tumour heterogeneity, a major determinant of resistance to treatment, remains unaddressed.
I therefore propose to identify and understand synthetic lethal vulnerabilities associated with two selected SWI/SNF defects of unmet need (PBRM1 and SMARCB1), and to further study how the latter can be exploited to stimulate the anti-tumour immune response. By using hypothesis-testing and -generating approaches including high-throughput screening on in-house developed isogenic and non-isogenic models, I will identify and decipher novel synthetic lethal vulnerabilities associated with PBRM1 and SMARCB1 defects. Molecular biology, high-content imaging and in vivo experiments will be performed to study the effects of drugs that cause synthetic lethality, both on intra-cellular signalling and on anti-tumour immune response. I will further characterise the impact of SMARCB1 defects on tumour heterogeneity using single cell sequencing on preclinical models and human tumour samples. Preclinical data will be integrated with tumour profiling and clinical data, and will guide the development of proof-of-concept clinical studies, as I previously did.
The overall research program will identify, decipher mechanistically and evaluate clinically novel immuno-oncology therapeutic strategies for selected SWI/SNF-deficient tumours of unmet need.
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 genetics DNA
- natural sciences biological sciences genetics mutation
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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)
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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)
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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
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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
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Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) ERC-2022-STG
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94805 Villejuif
France
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