James Wadkin

Title: Expression, regulation and the functional role of Tetraspin CD151 in the development of chronic liver disease and hepatocellular carcinoma

Summary: Liver disease is the only major cause of death still increasing year on year in the United Kingdom, with twice as many people dying from liver disease now than did twenty years ago. Despite the growing global burden, treatment strategies rely upon removal of the underlying causative agent or transplantation for end-stage disease. Patients with cirrhosis, the end-stage of all chronic liver diseases, are also at a higher risk of developing a primary liver cancer. The increased mortality associated with liver disease in the UK in the absence of effective treatment options, as well as the vast array of functions of the organ, initially attracted me to explore research projects associated with hepatology.

The aims of my project were to initially characterise the amount of a protein called CD151 in healthy control livers, chronic liver disease samples and liver cancer, before studying how this protein may drive liver disease through the recruitment of white blood cells into the organ; a process that is central to the establishment and progression of liver injury.

The amount of CD151 in diseased livers and tumour tissue was increased compared to that in subjects with normal, healthy livers. CD151 was found at key sites of immune cell recruitment in the liver and we showed that the protein was responsible for the migration of white blood cells into the liver. Crucially we demonstrated that this process could be inhibited by the addition of an antibody that blocks the function of CD151, raising the possibility that this protein may be a valuable target in the therapeutic treatment of inflammatory disease and cancer.