Epithelial Stem Cell Homeostasis and Cancer Most adult tissues are maintained by stem cells and failure to control the generation or differentiation of stem cells contributes to cancer. We use the mammalian skin as a model system to identify novel key regulators and pathways that control tissue homeostasis by regulating stem cell growth and differentiation. The skin is an essential barrier that protects our body against the external environment. The maintenance of the skin epidermis is tightly balanced and controlled by stem cells that continuously maintain their population (self-renewal) while generating progeny (differentiation). Skin stem cells are established during development and are retained in adulthood allowing the body to replace, restore and regenerate dead, damaged or diseased epidermal cells. How the balance between stem cell self-renewal and differentiation is controlled is not fully understood, yet knowledge of regulatory pathways controlling these two states is fundamental to determine how stem cell misregulation causes human diseases.
Michaela Frye Michaela Frye completed her PhD in Frankfurt/Main in Germany in 2000 studying the role of epithelial defensins in Cystic Fibrosis. In 2001 she joined the lab of Fiona Watt as a Postdoctoral Fellow at the CR-UK London Research Institute where she developed her fascination for the question how stem cells in the skin are regulated. Michaela received a CR-UK Career Development Fellowship in 2007 when she started as a group leader at the WT-MRC Stem Cell Institute. She has renewed this fellowship in 2012 and is now a CR-UK Senior Fellow.
Labelling stem cells (green) in skin; Blue staining: nuclei; Red Staining keratin
Driskell I., Oda H., Blanco S., Nascimento E.M., Humphreys P., and Frye M* (2012). The histone methyltransferase Setd8 acts in concert with c-Myc and is required to maintain skin. EMBO J. 31:616-29. PMID: 22117221
Cancer Research UK ERC British Skin Foundation Wellcome Trust
Nascimento E.M., Cox C.L., MacArthur S., Hussain S., Trotter M., Blanco S., Menon S., Nichols J., K端bler B., Aznar Benitah S., Hendrich B., Odom D.T., and Frye M* (2011). The opposing transcriptional functions of Sin3A and c-Myc are required to maintain tissue homeostasis. Nature Cell Biology. 13:1395-405. PMID: 22101514 Blanco S., Kurowski A., Nichols J., Watt F.M., Aznar Benitah S., Frye M* (2011). The RNA methyltransferase Misu (NSun2) poises epidermal stem cells to differentiate. PLoS Genetics. 7:e1002403. PMID: 22144916 Group Members Sandra Blanco Shobbir Hussain Jelena Aleksic Roberto Bandiera Iwona Driskell Martyna Popis Joana Flores Mahalia Page Abdul Sajini Nikoletta Gkatza Carolin Witte