Objective
A major gap in knowledge exists relating to the mechanisms via which a normal hematopoietic stem cell attains a fully transformed state via preleukemic intermediates. It is now accepted that a key player in this transition is epigenetic plasticity. Identifying the epigenetic mechanisms regulating the transformation of normal to leukemic stem cells will open new avenues for the identification of therapeutics at different stages of disease. A characteristic stem cell-like gene expression pattern is a hallmark of aggressive acute myeloid leukemia. Intriguingly, most of these patients harbour mutations in epigenetic modifiers that directly regulate stemness. What is fundamentally missing is a comprehensive understanding of which chromatin factors are involved in maintaining normal stem cell programs and how they are modulated during leukemic transformation. I recently uncovered a novel epigenetic mechanism of transition to the leukemic-state, mediated by direct chromatin binding of mutant NPM1 and transcriptional regulation of a specific set of stem-cell genes. This discovery, together with cutting-edge ultra-low-input chromatin technologies and our recently developed in vivo models of preleukemia, will serve as the springboard to address these fundamental questions:
1) How are normal hematopoietic stem cell programs regulated at the epigenetic level?
2) What are the epigenetic landscape alterations that govern tumorigenicity?
3) How can we exploit epigenetic dependencies to pharmacologically target the premalignant and/or malignant state?
EpiTransformers will delve into the largely unexplored epigenome during the leukemic transformation of rare stem cell populations using cutting-edge epigenetic profiling technologies and sophisticated in vivo models to deconvolute different steps of leukemogenesis and identify cancer specific vulnerabilities. The goal of EpiTransformers is to develop new therapeutic approaches by specific targeting of premalignant leukemic states.
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: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.
- natural sciences biological sciences genetics mutation
- medical and health sciences clinical medicine oncology leukemia
- natural sciences biological sciences genetics epigenetics
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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-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.
60323 Frankfurt Am Main
Germany
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