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David Fernandez-Antoran

fernandez-antoran

David Fernandez-Antoran, PhD

CRUK-RadNet Group Leader 

David’s lab has opened. If you are interested in joining the team, please directly.

Europe PMC | PubMed 

 

 

Radiation biology and cell competition

Healthy adult epithelial tissues progressively accumulate clones of cells carrying mutations implicated in cancer and their expansion follows Darwinian evolution rules. Some mutations can increase cell fitness and promote the growth of clones at the expenses of the non-mutated normal adjacent cells, in a process of clonal competition.

Ionising radiation has long been studied as one of the most common environmental mutagenic agents that promotes tumour formation by damaging DNA and creating new oncogenic mutations. However, little is known about its effects on clonal evolution and tissue dynamics. We have recently shown that it can act as a selective pressure, affecting cell competition mechanisms and promoting selection of pre-existing oncogenic mutations, which might increase the risk of cancer development.

We use long-term human and mouse 3D primary epithelial cultures, in vivo cell lineage tracing, mathematical modelling, next generation sequencing methods and state-of-the-art confocal microscopy techniques to unravel the molecular responses and the cellular interactions that control normal and mutant cell behaviours after exposure to different doses of ionising radiation.

The final aim of our research is to understand the effects of ionising radiation in tumours and normal tissues and set the basis for designing external interventions that can modulate cell competition outcomes, eliminate oncogenic mutations from tissues and reduce the risk of cancer initiation and progression.

Selected publications:

  • Piedrafita et al (2020) A single-progenitor model as the unifying paradigm of epidermal and esophageal epithelial maintenance in mice. Nature Communications doi.org/10.1038/s41467-020-15258-0
  • Fernandez-Antoran et al (2019) Outcompeting p53-mutant cells in the normal esophagus by redox manipulation. Cell Stem Cell doi.org/10.1016/j.stem.2019.06.011
  • Martincorena and Fowler et al (2018) Somatic mutant clones colonize the human esophagus with age. Science doi.org/10.1126/science.aau3879

Co-workers

David's lab is now open - if you are interested in joining the team, please directly.