The research in our lab is broadly divided into three areas.
Senescence and Development
Cellular senescence acts as a potent tumour suppressive mechanism, while it can also drive tissue aging and stem cell decline. Recently, while investigating possible non-classical functions for senescence, we discovered cellular senescence as a normal programmed process during embryonic development. This unexpected discovery opens up exciting new avenues to unravel the biological importance of the senescence program, its role in embryonic development and patterning, and the correlations with its function in cancer and aging. (Storer et al, Cell, 2013: Storer and Keyes, Comm. Int. Biol, 2014).
Stem Cells, Cancer and Aging
A primary determinant of tumour initiation is age i.e. cancer is a disease of aging. Given that cells expressing markers of hair follicle stem cells (HFSCs) in the skin are a suggested cell of origin during tumour initiation, we wanted to investigate how skin stem cells age, whether they undergo senescence, and if they are altered in their tumour-initiating capacity. Surprisingly, we discovered striking alterations in HFSCs during the normal aging process, opening up a new area of research investigating the molecular mechanisms of skin stem cell aging. (Doles et al, Genes Dev., 2012: Doles and Keyes, Aging, 2013: Ortells and Keyes, Biochem. Soc. Trans., 2014).
p63, Stem Cells, Senescence and Cancer
Another long-running interest in our lab is the mechanisms of tumour initiation and transformation. We recently discovered that ΔNp63α has oncogenic capacity in keratinocytes, and is able to initiate the development of Squamous Cell Carcinoma (SCC) directly by inhibiting the process of oncogene-induced senescence. In this study, we identified a new cancer causing mutation that provides an ideal model-system to investigate the early stages of tumour initiation and progression. Ongoing questions include the identification of novel p63-targets and stem cell genes that are involved in tumour initiation, and whether similar processes are also found in other tumour types. (Keyes et al, Cell Stem Cell, 2011).
- Investigating the role of p63 and aberrant stem cell proliferation in the pathogenesis of Squamous Cell Carcinoma.
- Determining the function of p63 in prostate stem cells and prostate tumour development.
- Exploring the role of cellular senescence in cancer, aging and development.
- Determining how epidermal stem cells change during normal aging, and the relationship to cancer formation.