Phil Jones

Stem cells and cancer

3D imaging of a 3 cell clone derived from individual epidermal progenitor cell genetically labelled 3 weeks previously, blue DNA stain, yellow EYFP.

Stem cells maintain tissues in adult life, and are regulated so that they generate exactly the right number of differentiating cells to balance cell loss from the tissue. Cancer is thought to arise from the mutation of stem cells. We are studying how this process occurs, and investigating the role of genes that regulate stem cell behaviour in the development of cancer.

Clonal evolution of cancer
We have developed a method to target specific mutations to individual progenitor cells in the epidermis and follow the fate of the cells and their daughters in vivo. We are now investigating the effects of expressing oncogenes in this system, allowing us to study the development of cancer from a single mutant cell into a tumour.

Xenopus embryo injected with Hes6 mRNA on the side shown, red muscle actin, blue DNA, green mRNA tracer.

Stem cell regulators in cancer
We are investigating whether genes that regulate stem cell fate are disrupted in cancer, focussing on the Notch pathway and the transcription factor Hes6, which regulates muscle and nerve stem cells and is a candidate oncogene in childhood cancers. We have used Xenopus embryos to demonstrate that Hes6 is required for normal myogenesis and produces in expansion of the myotome when overexpressed, and are also studying Hes6 expression and function in tumours and in cancer cell lines.

Contact

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Recent Publications

Hes6 is required for actin cytoskeletal organization in differentiating C2C12 myoblasts. Malone CM, Domaschenz R, Amagase Y, Dunham I, Murai K, Jones PH. Exp Cell Res. 2011 Apr 9. [Epub ahead of print]

Stem cell fate in proliferating tissues: equal odds in a game of chance. Jones PH. Dev Cell. 2010 Oct 19;19(4):489-90.

The ordered architecture of murine ear epidermis is maintained by progenitor cells with random fate. Doupé DP, Klein AM, Simons BD, Jones PH. Dev Cell. 2010 Feb 16;18(2):317-23.

Stochastic fate of p53-mutant epidermal progenitor cells is tilted toward proliferation by UV B during preneoplasia. Klein AM, Brash DE, Jones PH, Simons BD. Proc Natl Acad Sci USA. 2010 Jan 5;107(1):270-5.

A single type of progenitor cell maintains normal epidermis. Clayton E, Doupé DP, Klein AM, Winton DJ, Simons BD, Jones PH. Nature. 2007 Mar 8;446(7132):185-9.

To undertake world leading research into cancer cell biology that can be translated into clinical practice to improve the diagnosis and treatment of cancers.