Neutrophils are a phenotypically heterogeneous immune cell that can carry out a wide number of functions including the potential to contribute to cancer development. High numbers of liver neutrophils are a feature of alcoholic and non-alcoholic fatty liver diseases (NAFLD); the latter becoming a major global cause of cirrhosis and liver cancer. Neutrophils are observed within liver tumours and in peri-tumoral regions. Numbers of circulating neutrophils increase with grade of liver cancer and are associated with poorer quality of health and prognosis. Collectively these observations suggest potential roles for neutrophils in the initiation and growth of liver cancers. Using a genetic model of inflammatory dysregulation, the nfkb1-/- mouse1.2, we show that neutrophils promote hepatocellular lipid peroxidation, DNA damage, telomere damage and liver cancer. Antibody-mediated neutrophil depletion of neutrophils can be used as an interventional therapeutic approach to suppress tumour burden in a carcinogen-induced model of mouse liver cancer. Moreover, small molecule inhibitors of the neutrophil chemokine receptor CXCR2 protect against cancer in a combined NAFLD and carcinogen model of liver disease. Additionally, we are investigating mechanisms by which p50, the product of nfkb1, operates as a tumour suppressor. Finally, we are using the nfkb1-/- model to determine if modest exercise has interventional potential for liver inflammation and cancer.
I am a molecular cell biologist trained at University College London (PhD) and the MRC Laboratory of Molecular Biology (postdoc). In 2006 I was appointed Professor of Hepatology at Newcastle University following academic posts up to Chair position at the University of Southampton. I have established a world leading fibrosis research group investigating ageing-associated chronic diseases across multiple organs and that is supported by grants from UK research councils, charities and collaborations with major industrial partners including GSK and Abbvie. The scientific focus of my work is cell signaling with particular interest in epigenetic mechanisms and the regulation and physiological functions of NF-kB and AP-1 transcription factors. Recent publications from the laboratory include reports in Nature Medicine and Nature Communications. I am consultant for fibrosis drug discovery with many pharmaceutical and biotechnology companies and serve as a scientific advisory board member of Bird Rock Bio. In October 2016 I will take up the strategic post of Dean of Research of the Faculty of Medical Sciences at Newcastle University.