Dr Michaela Frye
Wellcome Trust Centre for Stem Cell Research
Basic biology (model organisms)
Cancer biology and in vivo models
Many adult tissues are maintained by stem cells. Failure to control the generation or differentiation of stem cells contributes to cancer. Our goal is to identify key regulators and mechanisms that control the maintenance of the epidermis by regulating stem cell growth and differentiation. The transcription factor Myc is well known for its role in tumourigenesis but its functions in non-malignant cells remain enigmatic. Our studies have revealed a key role for Myc in regulating adult stem cell homeostasis. Through its interaction with Miz1, Myc regulates the exit of stem cells from their niche by directly repressing adhesive factors. Once the stem cells have left their niche, Myc induces cell proliferation via growth promoting target genes, like the novel RNA methyltransferase Misu. The aim of our laboratory is to characterise the epigenetic and transcriptional changes induced by Myc that regulate epidermal stem cell fate.
Frye M, Fisher AG, and Watt FM, 2007. Epidermal stem cells are defined by global histone modifications that are altered by Myc-induced differentiation. PlosOne. 2:e763.
Frye M, and Watt FM, 2006. The RNA methyltransferase Misu (NSun2) mediates Myc-induced proliferation and is upregulated in tumors. Curr Biol. 16:971–81.
Frye M, Gardner C, Li ER, Arnold I, Watt FM, 2003. Evidence that Myc activation depletes the epidermal stem cell compartment by modulating adhesive interactions with the local microenvironment. Development. 130:2793–808.
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