Project description
Tracking cancer’s secret causes
Cancer is often explained in genetic terms, but identical cells cultured under the same conditions can respond very differently. This raises a crucial question: what really triggers the disease to take hold? To answer this, the ERC-supported IGNITE project aims to investigate inflammation-driven pancreatic cancer. Specifically, researchers will study how different inflammatory environments interact with the epigenetic history of a cell to decide its fate. By monitoring these occult signals at the cellular, tissue, and systemic levels, IGNITE expects to identify why some responses lead to malignancy and others do not. The findings could open new avenues for steering tumour growth towards more manageable outcomes.
Objective
The gene-environment interaction paradigm has long provided a framework for understanding the contribution of environmental cues to cancer initiation. However, recent perspectives reveal that even amongst genetically identical cells, responses to environmental variation can be remarkably diverse. When and how pathogenic gene-environment interactions effectively ignite cancer remains ambiguous.
IGNITE aims to explain what drives cancer initiation beyond genetics by dissecting (mal)adaptive responses to environmental variation at the cell, tissue, and organismal level, taking inflammation-driven pancreatic cancer as a disease paradigm. I hypothesize that qualitatively distinct forms of local and systemic inflammation, which I refer to as “inflammatory contexts”, direct tumor evolution in ways that are largely predetermined by epigenetic fingerprints integrating cells’ lineage, mutational, and environmental exposure history. Hence, I will (1) identify epigenetic determinants underlying the differential potential of pre-malignant and malignant cell states to sense, communicate and evolve within distinct inflammatory contexts; (2) define tissue-level hallmarks of pathogenic vs homeostatic inflammatory contexts, and develop new approaches to engineer immune cell states distinguishing each; and (3) dissect poorly understood links between pancreatic cancer risk and distal inflammatory disorders to uncover organismal mechanisms. IGNITE’s multi-layered perspective of cancer susceptibility and evolution will integrate methodologies to map and functionally interrogate molecular, cellular, tissue, and systemic traits in human samples and physiological models to establish causal relations.
In sum, IGNITE will unmask yet-unknown contextual determinants of cancer beyond genetic susceptibility. The project’s results, new methods and concepts will make it possible to rationally harness inflammatory cues for steering tumor evolution towards clinically manageable 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: 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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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)
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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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(opens in new window) ERC-2024-COG
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08028 Barcelona
Spain
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