Group: Cancer Research UK - Colorectal Tumour Biology group

Colorectal tumour cell survival mechanisms and chemoprevention

Despite epidemiological evidence to suggest that between 50-80% is preventable, colorectal cancer remains the second highest cause of cancer mortality in the UK. The central focus of my research group is to increase our understanding of key events in early colorectal carcinogenesis, including the importance of the tumour microenvironment for gene expression and function. The aim is to identify novel targets for chemoprevention which also have potential for adjuvant therapy.

Specific research interests:

• Dynamism in transcription factor function in response to microenvironmental stress provides new avenues for selective targeting of tumour cells and in this context, we have made the potentially exciting observation that BAG-1 (Bcl-2 associated athanogene) is a modulator of NF-κB signaling; this has implications for the regulation of a number of important pro-survival factors including the COX-2/prostaglandin, EGF and TGF-β pathways.
• We are particularly interested in the importance of the atypical p50 NF-κB  homodimeric signalling pathway in colorectal carcinogenesis. We have shown that the Bcl-3/NF-κB homodimeric complex can promote tumour cell survival via an AKT dependent pathway. The focus is now on the importance of this complex in tumour stem cells.
• We are actively investigating the role of Bcl-3/NF-κB homodimeric complexes in colorectal cancer progression and the impact of Bcl-3 expression on patient prognosis.
• Our interest in NF-κB signaling has lead us to study the regulation of epithelial NF-κB signaling in inflammatory bowel disease.  The aim is identify early markers of tumorigenic progression that could be used in the management of chronic bowel disease.  In addition, in collaboration with David Morgan, we are investigating the role of epithelial NF-κB complexes in the innate tumour immune response.