Objective
This project addresses the unmet clinical needs of sickle cell disease (SCD), the most common monogenic disorder worldwide, characterized by chronic inflammation, multi-organ involvement, and severely impaired erythropoiesis. SCD pathophysiology is driven by hemoglobin S polymerization, leading to vaso-occlusion (VOC) and acute chest syndrome (ACS), oxidative stress, and activation of innate immunity. Our multidisciplinary approach combines patient-driven biomarker studies, mechanistic investigations in human and mouse models, and exploration of innovative therapies. Preliminary data reveal that chronic bone marrow inflammation impairs hematopoietic stem/progenitor cell functions, alters erythroid differentiation, and increases myeloid bias, all contributing to poor transplant and gene therapy outcomes. Novel research in our group highlights the role of non-canonical histidine phosphorylation (NME1/NME2) in regulating BCL11A activity for fetal hemoglobin synthesis, and demonstrates that pharmacological targeting of these kinases safely induces HbF in human progenitors. We also uncover critical roles for mast cells and basophils, showing that their activation drives pain, vaso-occlusion, and neuroinflammation. Candidate drugs, including masitinib, luspatercept, and anti-inflammatory agents, are tested for their ability to improve hematopoiesis, reduce acute and chronic complications, and modulate the bone marrow niche. By integrating high-throughput sequencing, multi-omic profiling, and advanced mouse genetics, this project aims to identify new biomarkers and therapeutic strategies to personalize SCD care, improve gene therapy success, and rapidly translate findings from bench to bedside, offering hope for patients globally.
Fields of science (EuroSciVoc)
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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-2025-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.
75205 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.