Cellular and molecular mechanisms that control primary liver, cell survival in health and disease

Group leader: Dr Simon Afford

Overview

Chronic inflammation which fails to resolve is a characteristic feature of many life threatening liver diseases including primary biliary cirrhosis, primary sclerosing cholangitis, hepatitis, alcoholic liver disease, liver allograft rejection and liver cancer. The overall aim of Dr Afford’s research is to investigate the basic mechanisms that regulate inflammatory responses in the liver. Severe inflammation can lead to permanent tissue damage including fibrosis, loss of organ function and in some cases malignant disease including hepatocellular and cholangiocarcinoma. My group focuses predominantly on the cell and molecular mechanisms which control primary liver cell survival including the intracellular signalling pathways which direct cholangiocyte and hepatocyte survival, apoptosis, autophagy, and cellular transition.

Our research group

Group Members

Mr Ricky Harminder Bhogal – Clinical Lecturer

Dr Phillip Kitchen – Post Doctoral Research Fellow (MRC project)

Mr Richard Laing - Clinical Research Fellow

Dr Yuri Boteon Longatto - Clinical Research Fellow

Mr Barnaby Stephenson

Lorraine Wallace

Hardeep Judge

Katrina Lee

Publications

Mergental H, Perera M, Laing RW, Muiesan P, Isaac JR, Smith A, Stephenson B, Cilliers H, Neil D, Hübscher SG, Afford SC and Mirza DF (2016) Transplantation of Declined Liver Allografts Following Normothermic Ex-Situ Evaluation. Am J Transplant 16(11):3235-3245

Wilhelm A, Shepherd EL, Amatucci A, Munir M, Reynolds G, Humphreys E, Resheq Y, Adams DH, Hübscher S, Burkly LC, Weston CJ and Afford SC (2016) Interaction of TWEAK with Fn14 leads to the progression of fibrotic liver disease by directly modulating hepatic stellate cell proliferation. J Pathol 239(1):109-21

Bhogal RH, Weston CJ, Curbishley SM, Adams DH and Afford SC (2012) Autophagy: A Cyto-Protective Mechanism which Prevents Primary Human Hepatocyte Apoptosis During Oxidative Stress. Autophagy 8(4):545-58

Afford SC, Randhawa S, Eliopoulos AG, Hubscher SG, Young LS and Adams DH (1999) CD40 activation induces apoptosis in cultured human hepatocytes via induction of cell surface FasL expression and amplifies Fas mediated hepatocyte death during allograft rejection. J Exp Med 189(2):441-6