Project description
Safer haematopoietic stem cell transplantation
Haematopoietic stem cell transplantation (HSCT) involves the intravenous infusion of haematopoietic stem cells in order to re-establish blood cell production. Although it can be a life-saving treatment for severe blood and immune disorders, it is associated with toxicity and low engraftment rates. The ERC-funded eHSCT project aims to develop safer and more effective strategies to overcome these challenges. Researchers will use genome-wide screening to uncover key regulators of stem cell engraftment and movement in order to improve current mobilisation and transplantation approaches. Moreover, the project will explore alternative non-toxic conditioning strategies to improve the engraftment of infused cells. Collectively, project innovations are expected to make HSCT safer and less toxic.
Objective
Hematopoietic stem cell transplantation (HSCT) is a groundbreaking therapy that has transformed the treatment of severe hematological and immune disorders. It involves infusing healthy or corrected hematopoietic stem cells (HSCs) into a patient to restore their blood cell production. Despite its remarkable success, HSCT is currently limited to the most severe cases due to several key challenges. These bottlenecks include inefficient HSC mobilization, limited engraftment leading to insufficient clonal diversity, and the toxicity of chemotherapy-based conditioning regimens.
This comprehensive proposal outlines a transformative approach to address these limitations head-on, enhancing both the efficacy and safety of HSCT.
The project aims to:
1. Uncover the key factors governing HSC engraftment and egress: Using optimized genome-wide gain- and loss-of-function in vivo screening in HSCs, I will identify the pivotal players responsible for HSC engraftment and egress. These insights will inform the development of innovative mobilization strategies and the engineering of HSCs to confer a transient engraftment advantage.
2. Establish a mobilization-based conditioning regimen: I will exploit the temporary niche depletion induced by mobilizers to optimize a genotoxic-free regimen. By harnessing cell surface profiling data and potentially using mobilizer-resistant variants generated through directed evolution, I will tilt the competitive balance between freshly mobilized and infused HSCs, favoring the engraftment of infused cells.
This project seeks to pioneer avant-garde methods that enhance mobilization and engraftment while avoiding the use of toxic conditioning regimens, thereby addressing major HSCT limitations. These advancements hold the potential to transform HSCT into a safer, more broadly applicable therapy, extending its benefits to a wider demographic and diverse healthcare settings. This aligns with the ultimate objective of achieving global health equity.
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.
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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-2024-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.
20132 Milano
Italy
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