Objective
MAIN GOAL: To characterize the metabolic changes, fuelling growth of tumor endothelial cells (TECs) versus normal healthy endothelial cells (NECs), and identify & validate metabolic genes, deregulated in TECs, as targets for anti-angiogenic cancer therapy.
BACKGROUND & RATIONALE: Tumors stimulate blood vessel growth (angiogenesis) to nourish cancer cells, but current anti-angiogenic treatments lack sufficient efficacy. NECs are widely used for anti-angiogenesis development, but TECs, the real target cells, have been dismissed, even though they differ fundamentally from NECs. We pioneered NEC metabolism research and demonstrated that inhibition of specific metabolic pathways can block angiogenesis. Nothing is however known on TEC metabolism. I hypothesize that TECs “hyper-activate” their metabolism in a tissue-specific manner, and that targeting TEC metabolism is a novel concept for inhibiting tumor angiogenesis.
METHODOLOGY: We will perform a transcriptomic and metabolomic analysis of TECs & NECs isolated from cancer patients, use an in-house developed bioinformatics platform (BIOMEX) to analyze the omics data in order to rank deregulated metabolic genes, and construct TEC-tailored genome scale metabolic network models (GEMs) allowing in silico computational modeling to predict metabolic targets that affect TEC but not NEC growth. The in vitro angiogenic activity of top targets will be biologically validated directly or after a negative selection shRNA-based screen, followed by validation in preclinical tumor models in vivo, using conditional knockout mice. All procedures are operational. Deliverables include in vivo validated metabolic targets, driving tumor angiogenesis.
NOVELTY, OVERALL & CLINICAL IMPACT: These pioneering studies on TEC metabolism promise to open up new horizons/opportunities for cancer research. Treatment with inhibitors of the validated targets promises to normalize hyperactive TEC metabolism as a novel anti-angiogenic cancer therapy.
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.
- natural sciences biological sciences cell biology cell metabolism
- medical and health sciences clinical medicine oncology
- natural sciences biological sciences genetics genomes
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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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H2020-EU.1.1. - EXCELLENT SCIENCE - 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
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.
ERC-ADG - Advanced Grant
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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-2016-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.
9052 ZWIJNAARDE - GENT
Belgium
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