Douglas Winton scientific summary

Epithelial stem cells and cancer

Previous and current research

The greatest number of cancers occur in the epithelial linings of major organs such as the intestine which are maintained by small numbers of long lived stem cells. It is by disruption of the normal molecular controls regulating stem cell growth, behaviour and programming that cancers develop.

The Winton group seeks to understand the normal biology of epithelial stem cells, and how this is subverted to allow cancers to form. Particular goals are to investigate stem cells in situ in their normal context and to determine the capacity of individual categories of cell to maintain and propagate cancers.

Future projects

Research topics include:

• Develop and apply strategies to induce specific gene mutations within epithelal tissues in a transgenic setting.
• Develop a mitotic clock to determine the frequency of stem cell division.
• To determine the composition and heterogeneity of stem cells in terms of their commitment to different cell lineages and proliferative potential.
• To determine the molecular pathways controlling stem cell fate and behaviour.
• To understand to what extent the stem cell characteristics of normal tissues are retained in epithelial cancers and if these can be exploited to develop therapeutic interventions.
• To understand at a cellular level how cancer predisposing mutations lead to the growth of neoplastic lesions.
• To test the efficacy of different therapeutic and preventative interventions applied at a defined stage of cancer growth.