Dr Philip Coates

My research focuses on the responses of cells and tissues to ionizing radiation exposure. Working with Prof Eric Wright, we have shown that the response to exposure depends on tissue type, cell type and genetic background. In addition to the directly damaging effects of ionizing radiation, tissue damage also causes changes to tissue microenvironments that persist for prolonged periods of time. These alterations show features of inflammatory processes and are either pro- or anti-inflammatory, depending on genetic background. The sustained inflammatory-type environment is associated with increased levels of ongoing DNA damage and the presence of activated macrophages that are capable of inducing new DNA damage in other cells. These studies indicate that the complex interplay of tissue specific responses to direct and indirect damage underlies the genetic susceptibility to radiation-induced acute myeloid leukaemia. Current research is aimed at delineating the pathways involved in producing and sustaining a damaging microenvironment. In other studies performed with Prof Alastair Thompson in the Breast Cancer Research Group and the Intra-Operative Radiotherapy Group, models of human breast epithelium are being developed to investigate the DNA damage response pathways that operate in this tissue.

Collaborative work with Dr Karin Nylander in Umea, Sweden investigates the function of the human p63 protein, which regulates epithelial stem cells and provides resistance to radiotherapy and chemotherapy in tumour cells. With Dr Rudolf Nenutil and Dr Borek Vojtesek in Brno, Czech Republic, we have developed an improved method for the identification of p53 mutation status in clinical tumour material. Ongoing work is investigating whether different types of p53 mutation give rise to different patterns of protein stabilization, whether these patterns provide prognostic information and whether inhibition of chaperones can de-stabilize specific p53 mutant proteins and reduce the gain of function effects of mutant p53.

Lorimore SA, Chrystal JA, Robinson JI, Coates PJ , Wright EG (2008) Chromosomal instability in unirradiated haemopoietic cells induced by macrophages exposed in vivo to ionizing radiation. Cancer Res 68: 8122-8126.

Coates PJ, 450-456. Rundle JK, Lorimore SA, Wright EG (2008) Indirect macrophage responses to ionizing radiation: implications for genotype-dependent bystander signaling. Cancer Res 68: