Objective
Burkitt lymphoma (BL) is an aggressive and fast-growing type of non-Hodgkin B-cell lymphoma, characterised by chromosomal translocations involving MYC in nearly 95% of cases. TPL2 is a cytoplasmic kinase positioned at the intersection of ERK/JNK and NF-κB signaling cascades, and has been characterized as acting either as an oncogene or as a tumor suppressor in diverse solid and hematological malignancies. Preliminary data generated in BL cell lines and primary samples, indicate an inverse correlation between MYC expression and TPL2 levels underpinned by putative direct transcriptional repression. Furthermore, low TPL2 levels have been correlated with enhanced disease aggressiveness in the BL-prone Eμ-myc mouse model. Thus, we hypothesize that any MYC-dependent tuning of TPL2 would directly reprogram pathways that sustain BL growth and stress adaptation. In the proposed project, we will follow a comprehensive experimental approach taking advantage of both human cell lines and mouse models combined with high throughput omics technologies. The proposal will be divided in three intercorrelated work packages. In WP1, we will identify the mechanism by which MYC transcriptionally regulates TPL2 in BL cell lines, by combining genetic engineering, gene regulation and functional analysis. In WP2, we will integrate mouse models and single-cell omics to define the B-cell–intrinsic role of TPL2 in MYC lymphomagenesis in vivo, while in WP3, will be determined whether TPL2 status predicts or modulates response to direct MYC antagonists, through the integration of in vitro and in vivo strategies. The proposed project will give insight into the molecular mechanisms of MYC-mediated regulation of TPL2 expression and function, which is mechanistically important for Burkitt lymphoma and may extend to other MYC-driven malignancies (such as subsets of DLBCL and high-grade lymphomas), thereby supporting biomarker-guided precision therapies with emerging direct MYC inhibitors.
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.
- medical and health sciences medical biotechnology genetic engineering
- natural sciences mathematics pure mathematics mathematical analysis functional analysis
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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.1.2 - Marie Skłodowska-Curie Actions (MSCA)
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
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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-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships
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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) HORIZON-MSCA-2025-PF
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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.
105 61 ATHINA
Greece
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.