Grant: CIHR Fellowship

Skin-the largest organ in our body-forms a crucial barrier between our internal tissues and the external environment. It is also the site of skin appendages, such as hair follicles and sweat glands, that are necessary to allow us to survive in changing climates. In particular, the mammalian hair follicle undergoes serval cycles of growth, destruction and rest, which necessitates multiple rounds of hair generation. A key component of all adult tissues, including hair follicles, are stem cells that retain the capability to become any of a number of more differentiated cell types. In the adult hair follicle, stem cells are responsible for giving rise to the differentiated hair in each round of hair generation, as well as contributing to wound healing when the skin is damaged. These are the cells that are also the origin of squamous cell carcinomas, a common and potentially life-threatening cancer. Despite the absolute importance of these cells, currently we have an incomplete molecular and cell biological picture of how skin stem cells are specified and maintained, and how this goes awry in disease states. This proposal aims to expand our knowledge of this important field in the hope that the biology elucidated may translate into functional insight into the establishment and maintenance of adult stem cells in normal and disease states. To achieve this, I have devised a loss-of-function genetic screen to assess the importance of each candidate specifically in hair follicle stem cell identity. I have also designed a second rapid way to conditionally knockout my top candidates from the screen and test them rigorously for their long-term functional relevance in normal hair cycling. Together, this will allow me to define novel molecular mechanisms that determine adult stem cell function, which in turn can be investigated for their impact on disease.