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Acquired Chromosomal Alterations Driving Inflammation

Objetivo

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.

Ámbito científico (EuroSciVoc)

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Programa(s)

Tema(s)

Régimen de financiación

HORIZON-ERC - HORIZON ERC Grants

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Convocatoria de propuestas

(se abrirá en una nueva ventana) ERC-2026-STG

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Institución de acogida

HELSINGIN YLIOPISTO
Aportación neta de la UEn
€ 1 499 669,00
Dirección
FABIANINKATU 33
00014 Helsinki
Finlandia
Región
Manner-Suomi Helsinki-Uusimaa Helsinki-Uusimaa
Tipo de actividad
Higher or Secondary Education Establishments
Enlaces
Coste total
€ 1 499 669,00

Beneficiarios (1)