Bone morphogenetic protein signalling and stromal-epithelial interaction in intestinal inflammation and carcinogenesis

Cancer is often described as the ‘wound that never heals’, and inflammation, wound repair and cancer are inextricably linked. This is because many of the chemical message networks that restrain and control epithelial stem cell growth in health are deranged in both wound repair and cancer. During regeneration, temporary signalling disruption from wounding allows cells to divide to replace those lost. With cancer, permanent disruption of signalling pathways leads to unrestrained cell division, one of the key hallmarks of malignancy. 

This project focuses on a key signalling pathway called bone morphogenetic protein (BMP). A team of gastroenterology scientists will use human tissue and biological models to explore how BMP signalling is temporarily disrupted during wound repair and to see how these important functions can be co-opted and corrupted by cancer. 

We aim to identify cells responsible for expression of BMP constituents in healthy tissue, wounds and cancer, to understand how this signalling pathway affects wound repair and tumour growth and to test potential new drugs that affect BMP signalling.  We will also use characteristic mutation patterns to identify human tumours that originate from BMP disruption and see if they behave differently to other cancers.