SubsidieMeestersCell size as driver of stem cell aging and cancer
This project aims to investigate how cellular enlargement affects stem cell function and aging, potentially linking size to rejuvenation and cancer development, using mouse models for insights.
Projectdetails
Introduction
The failure to regenerate tissue underlies a challenging health issue in the elderly. A main contributor to this decline is the loss of stem cell function during aging. Despite the essential role of stem cells, it is unclear how they fail to maintain their functions during aging and disease. I discovered a new aspect of stem cell aging in vivo: cellular enlargement. With age, stem cells increase in size leading to their functional decline. However, it is unclear how size impacts stem cell fitness. Moreover, the physiological importance of this process remains unsolved.
Research Objectives
My team at the University of Helsinki will address these questions by:
- Identifying pathways that promote stem cell dysfunction during enlargement.
- Assessing the effects of size reduction on stem cell rejuvenation.
- Illuminating the effects of stem cell size on cancer.
Hypothesis and Methodology
Supported by preliminary data, I hypothesize that cell size is a driver of stem cell aging and cancer. Using hematopoietic stem cells (HSCs) of mouse models, I will identify the molecular mechanisms impairing the fitness of large HSCs.
I will also perform a screen to identify pathways that modulate the size of HSCs to test for rejuvenation. These will allow me to establish how HSC size affects other cellular aging pathways, organismal health, and whether this relationship is causal or correlative.
I hypothesize that cellular size impacts HSCs to transform into cancerous cells. To test this, I will use differently sized, oncogenic HSCs from mice and humans to test their potential to facilitate leukemia in vivo and to investigate the underlying mechanisms of this process.
Potential Impact
The novel concepts outlined here have exceptional potential for scientific impact as they add a new paradigm to stem cell aging, provide transformative treatment perspectives, and examine cancer from a new dimension.
Financiële details & Tijdlijn
Financiële details
| Subsidiebedrag | € 1.500.000 |
| Totale projectbegroting | € 1.500.000 |
Tijdlijn
| Startdatum | 1-1-2024 |
| Einddatum | 31-12-2028 |
| Subsidiejaar | 2024 |
Partners & Locaties
Projectpartners
- HELSINGIN YLIOPISTOpenvoerder
Land(en)
Vergelijkbare projecten binnen European Research Council
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|---|---|---|---|---|
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This project aims to develop a game theoretic framework to analyze the psychological and strategic dynamics of collaborative exploitation, informing policies to combat modern slavery.
Elucidating the phenotypic convergence of proliferation reduction under growth-induced pressure
The UnderPressure project aims to investigate how mechanical constraints from 3D crowding affect cell proliferation and signaling in various organisms, with potential applications in reducing cancer chemoresistance.
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This project aims to uncover the mechanisms behind Wolbachia's antiviral protection in insects and develop tools for studying symbiont gene function.
The Ethics of Loneliness and Sociability
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Vergelijkbare projecten uit andere regelingen
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|---|---|---|---|---|
Cellular models for tissue function in development and ageingDevelop a computational framework to model cellular interactions in tissues, enabling insights into dynamics and gene regulation for applications in cell engineering and immunotherapy. | ERC ADG | € 2.937.179 | 2023 | Details |
The Interplay of Aging, Immune Signaling and Stem Cell FunctionThis project aims to investigate how immune environment changes contribute to muscle stem cell dysfunction and regenerative decline in aging, with the goal of improving stem cell therapies. | ERC COG | € 1.998.843 | 2024 | Details |
Mutations in healthy tissues: a double-edged sword for tissues homeostasisThis project investigates how somatic mutations enhance the fitness of stem/progenitor cells to maintain tissue integrity and regenerative potential, linking ageing, mutations, and disease risk. | ERC SyG | € 9.808.142 | 2025 | Details |
Cellular models for tissue function in development and ageing
Develop a computational framework to model cellular interactions in tissues, enabling insights into dynamics and gene regulation for applications in cell engineering and immunotherapy.
The Interplay of Aging, Immune Signaling and Stem Cell Function
This project aims to investigate how immune environment changes contribute to muscle stem cell dysfunction and regenerative decline in aging, with the goal of improving stem cell therapies.
Mutations in healthy tissues: a double-edged sword for tissues homeostasis
This project investigates how somatic mutations enhance the fitness of stem/progenitor cells to maintain tissue integrity and regenerative potential, linking ageing, mutations, and disease risk.