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Identification and characterization of novel essential regulators of acute myeloid leukemia

Objective

Acute myeloid leukemia is a hematopoietic malignancy characterized by the abnormal proliferation of immature myeloid cells. The implementation of high-throughput sequencing revealed that somatic mutations in various epigenetic regulators represent a frequent pathogenic phenomenon in leukemogenesis. This raised optimism for the development of new therapies in leukemia due to the reversible nature of epigenetic marks and amenability of chromatin-modifying enzymes to pharmacological inhibition. However, realization of this potential requires further research into epigenetic mechanisms governing the maintenance of leukemic cells. The overall goal of the proposed work is to characterize novel important epigenetic regulators in leukemic cells and to assess their potential as drug targets. Firstly, I plan to identify and study epigenetic regulators essential for leukemic cells deficient in TET2, an enzyme that hydroxylates methylated cytosines in DNA. This will be achieved by performing state-of-the-art shRNA screens in mouse Tet2-null leukemia models and by exploring the functions of the uncovered candidates using a range of cell biology, biochemistry, and functional genomics approaches. The second aim is to investigate the molecular functions of SETD5, a newly-uncovered epigenetic regulator of leukemic cells. This will be achieved by identifying its target genes and interacting partners in leukemic cells and by exploring the effects of its depletion on normal and cancer cells. The accomplishment of both research aims will provide new insights into epigenetic regulation of leukemic cells and highlight novel drug targets for future therapy development. The project will be supervised by Prof Kristian Helin, a world-leading expert in the field of epigenetics and cancer. Through this work, I aim to broaden my scientific expertise by acquiring numerous technical and transferable skills and to establish myself as an independent researcher in the field of cancer epigenetics.

Fields of science (EuroSciVoc)

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Programme(s)

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Topic(s)

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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.

MSCA-IF-EF-ST - Standard EF

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Call for proposal

Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.

(opens in new window) H2020-MSCA-IF-2014

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Coordinator

KOBENHAVNS UNIVERSITET
Net EU contribution

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.

€ 212 194,80
Address
NORREGADE 10
1165 KOBENHAVN
Denmark

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Region
Danmark Hovedstaden Byen København
Activity type
Higher or Secondary Education Establishments
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Total cost

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.

€ 212 194,80
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