Dr Michaela Frye
Stem Cell Homeostasis and Disease
Stem cells are established during development and remain present in adulthood allowing the body to replace, restore and regenerate dead, damaged or diseased cells. Stem cells continuously maintain their population (self-renewal) while generating progeny (differentiation). During self-renewal stem cells have to avoid cell cycle exit and differentiation; whereas during differentiation stem cells must evade uncontrolled proliferation. Dissecting the regulatory pathways controlling the balance between these two states is fundamental to understanding how stem cell mis-regulation causes human diseases and cancer.
While transcriptional regulation of stem cells is increasingly understood, virtually nothing is known about how post-transcriptional mechanisms can influence stem cell maintenance. Post-transcriptional modifications are commonly found in non-coding RNA species and our recent studies identified cytosine-5 methylation (m5C) of RNA as a novel mechanism regulating stem cell fate.
To dissect the cellular and molecular functions of cytosine-5 methylated RNA, we are using a combination of system-wide approaches, mouse models and in vitro differentiation assays. Our comprehensive approach will answer how post-transcriptional modification controls stem cell fate in normal tissues and how aberrant cytosine-5 methylation pathways can cause human diseases including cancer.