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Common Mechanisms of Development, Cancer and Aging

Common Mechanisms of Development, Cancer and Aging

DEPARTMENT

Development and stem cells

TEAM LEADER

Bill KEYES

Cellular Senescence
Cellular Senescence is a state of irreversible cell cycle arrest induced in response to a variety of stimuli, including tissue and cellular damage, inflammatory signals and developmental cues. However, despite being arrested from the cell cycle, senescent cells remain highly active, and interact with their environment through a complex secretome known as the senescence-associated secretory phenotype (SASP). The research in our lab is focused on the study of cellular senescence.

A primary function of senescence is to prevent proliferation of damaged cells, and it therefore acts as a tumor-suppressive mechanism that protects from cancer. Furthermore, the abnormal or chronic accumulation of senescent cells contributes to the aging process, and to many disease states. However, work from our group and others has identified that in certain situations, senescent cells can have beneficial functions, including during embryonic development and in tissue regeneration. We are therefore interested to understand the biological functions of cellular senescence in both physiological and pathological states, its mechanisms of action, and the consequences of its misregulation.

Members

Researchers

Post-doctoral fellows

Current projects

What is the role of cellular senescence during development?
    We previously identified that programmed cellular senescence is a normal feature of embryonic development (Storer et al, 2013). We are investigating the functions, and molecular regulation of developmental senescence in a variety of models.

Is aberrant senescence linked to developmental birth defects?
    Aberrantly induced or chronic senescence is detrimental, contributing to the aging process and multiple diseases. However, it is not clear if mis-timed or ectopic senescence contributes to developmental defects and disorders. We are investigating whether alterations in senescence may contribute to developmental disorders (e.g. Rhinn et al, BioRxiv, 2021).

How does transient senescence contribute to cell plasticity and tissue regeneration?
    We have shown that transient exposure to the SASP can induce cellular plasticity and stem cell fate. We demonstrated this in skin, showing how keratinocytes exposed to the SASP become functional hair-follicle stem cells (Ritschka et al, 2017). We are exploring how the SASP can instruct such changes in cell fate, and the functional consequences of this interaction in both physiological and pathological settings, such as cancer.

How does mis-timed senescence contribute to disease, such as cancer or neurodegeneration?
The aberrant induction of senescence contributes to aging and disease. We recently identified how senescence-like changes may develop in a heterogenous manner and block tissue regeneration (Ritschka et al, 2020). We are investigating how senescence contributes to diseases such as cancer and neurodegeneration.

Can we identify novel cellular features or bio-markers of cellular senescence?
    Senescent cells are very heterogenous and are difficult to identify in vivo. We are performing cell-based studies to identify novel markers and features of the dynamic senescence program.

Funding and partners

The team has been generously supported by funding from:

  • Fondation Recherche Medicale (FRM)
  • Fondation ARC pour la Recherche sur le Cancer (ARC)
  • Worldwide Cancer Research
  • La Ligue Contre le Cancer
  • IDEX, University of Strasbourg
  • Fonds National de la Recherche (FNR), Luxembourg
  • Agence Nationale de la Recherche (ANR)
  • Fondation Schlumberger

Awards and recognitions

  • 2018    Academy of Sciences Cancer Research Prize from the Simone and Cino Del Duca Foundation
  • 2018    Schlumberger Foundation award for research and education (Laureate)
  • 2016     INSERM Research Director (Level DR2)
  • 2013     The City of Barcelona Prize for Life Sciences

Publications

Development and stem cells - Cancer research - Rare diseases - Regenerative medicine