Objective
Systemic inflammation is a hallmark of aging and a major global health challenge. Aging leads to the expansion of clonal hematopoietic stem cells (HSCs), and HSC clones carrying acquired genetic alterations, including mosaic chromosomal alterations (mCAs), are referred to as clonal hematopoiesis (CH). While mCAs are common in patients with hematologic malignancies, mCA-driven CH also becomes highly prevalent in aging populations in the absence of hematologic neoplasia. This emerging paradigm suggests that clonal expansion of HSCs may act as a silent systemic driver of inflammation and aging-related pathologies. However, how mCAs contribute to the pathogenesis of age-associated diseases remains unknown, and addressing this knowledge gap may help reduce the morbidity burden associated with aging. Our preliminary results point towards a mechanistic link between mCAs and inflammatory diseases. In this project, I will leverage large population-level cohorts with genetic information and richly annotated longitudinal clinical data, systematic longitudinal blood sampling, cutting-edge multiomic single-cell and bioinformatics approaches, as well as hypothesis-driven genetic engineering in cell line models, to discover the clinical and functional impact of mCAs in regulating inflammation. We aim to 1) characterize the natural history of CH in patients with inflammatory diseases, 2) elucidate how mCAs impact immune cell differentiation and function, and 3) identify cell-extrinsic selection pressures driving clonal expansion of mCAs. Collectively, an increased understanding of the inflammatory processes driven by mCAs may enable personalised treatment and surveillance strategies in inflammatory diseases and cancer that are strikingly common in the general population, with potential implications for alleviating inflammation also in the context of aging.
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Keywords
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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)
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.
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-2026-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.
00014 Helsinki
Finland
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