Dr Michaela Frye
Epithelial Stem Cell Homeostasis and Cancer
Email: mf364@cscr.cam.ac.uk
Laboratory Location:
Wellcome Trust, Centre for Stem Cell Research, Frye Lab Members
Departmental Affiliation:
Department of Physiology, Development and Neuroscience, University of Cambridge
Co-workers:
• Sandra Blanco • Claire Cox • Iwona Driskell • Joana Flores • Shobbir Hussain
Learn more about Dr Michaela Frye
Michaela Frye completed her PhD in Frankfurt/Main 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 c-Myc and its role in regulating the stem cell compartment in skin.
Michaela received a CR-UK Career Development Fellowship in 2007 when she started as a group leader at the CSCR.
Lab Information
Many adult tissues are maintained by stem cells. Failure to control the generation or differentiation of stem cells contributes to cancer.
The goal of our laboratory is to identify key regulators and mechanisms that control the maintenance of the epidermis by regulating stem cell growth and differentiation. In particular, we focus on transcriptional and post-transcriptional mechanisms regulating the balance between epidermal stem cell self-renewal and differentiation.
The importance of post-transcriptional regulation is highlighted by the fact that only 20-40% of cellular protein concentrations are directly determined their corresponding mRNA concentrations. We recently identified RNA methyltransferases as important players in maintaining tissue homeostasis. One of our research aims is to uncover the precise functional roles of the post-transcriptional modification of cytosine-5 in RNA. RNA methylation pathways are a novel and unexplored field of research and promise interesting and important findings of how stem cells are regulated in both normal and diseased tissues.
To answer our research questions we are using a combination of genome-wide systems biology approaches and in vivo models.
Plain English
Most tissues are maintained by stem cells throughout adult life. Stem cells are defined by their ability to continuously maintain their population (self-renewal) while generating differentiated progeny. During self-renewal, stem cells have to avoid cell cycle exit and differentiation; however, when differentiating they have to evade uncontrolled proliferation. How the balance between self-renewal and differentiation is regulated is not fully understood but yet highly relevant to a fundamental understanding of cell biology and human diseases. Aim of our research is to identify key factors regulating stem cell differentiation in adult tissues because important stem cell regulators are often mis-regulated in human diseasesKey Publications
View all publications by
Dr Michaela Frye
Driskell I., Oda H., Blanco S., Nascimento E.M., Humphreys P., and Frye M. 2011. The histone methyltransferase Setd8 acts in concert with c-Myc and is required to maintain skin. EMBO J. 31:616-29.
Nascimento E.M., Cox C.L., MacArthur S., Hussain S., Trotter M., Blanco S., Menon S., Nichols J., Kübler 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.
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.
Luis N. M., Morey L., Mejetta S., Pascual G., Janich P., Kuebler B., Cozzutto L., Roma G., Nascimento E., Frye M., Di Groce L., Aznar Benitah S. 2011. Regulation of human epidermal stem cell dormancy and senescence requires Polycomb-dependent and –independent functions of Cbx4. Cell Stem Cells. 9:233-46.
Hussain S., Benavente S.B., Nascimento E., Dragoni I., Kurowski A., Gillich A., Humphreys P., Frye M. 2009. The nucleolar RNA methyltransferase Misu (NSun2) is required for mitotic spindle stability. J Cell Biol. 186:27-40.
Watt F.M., Frye M., Aznar Benitah S. 2008. Myc in mammalian epidermis: how can an oncogene stimulate differentiation? Nat Rev Cancer. 8:234-42.
Frye M. and Watt F. M. 2006. The RNA methyltransferase Misu (NSun2) mediates Myc-induced proliferation and is upregulated in tumors. Curr Biol. 16:971-81.