; The Francis Crick 台湾swag
William was awarded his PhD from Cardiff University for his work on cell competition at the earliest stages of pancreatic cancer. He demonstrated that KrasG12D mutant cells are selectively eliminated by normal neighbours from the adult pancreas in vivo. William joined the group of Professor Charles Swanton in Autumn 2019 at the Crick studying how environmental exposures combine with somatic mutations to promote lung cancer.
A complete understanding of how environmental exposures promote cancer formation is lacking. Over 70 years ago, tumour formation was proposed to occur in a two-step process: an initiating step which induces mutations in normal cells, followed by a promoter step which triggers cancer development. We hypothesised that environmental particulate matter measuring <2.5渭m (PM2.5), known to be associated with lung cancer risk, promotes EGFR mutant lung cancer by acting on cells harbouring pre-existing oncogenic mutations in normal lung tissue. We combine epidemiological evidence, functional pre-clinical mouse models and ultra-deep sequencing of normal tissue from clinical cohorts to decipher potential mechanisms of air pollutant induced tumour promotion. We propose that PM2.5 can trigger the expansion of pre-existing mutant lung cells via an inflammatory axis and this mechanism may be applicable to a range of cancer risk factors.
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