Hepatology and Gastroenterology Research Group

• 
  Professor
  Peter Angus

  Peter.Angus@austin.org.au

  +61 3 9496 5582

• 
  Honorary Senior Research Fellow
  Dr Chandana Herath

  cherath@unimelb.edu.au

Research Overview

Liver fibrosis and its end-stage sequelae of cirrhosis and liver cancer are major causes of morbidity and mortality in Australia and throughout the world and their prevalence is rising, largely due to the increasing impact of chronic liver diseases including non-alcoholic fatty liver disease (NAFLD) and biliary diseases. It is hoped better disease prevention and more effective therapies will help reduce this disease burden. However, there remains a major need to identify potentially modifiable factors which exacerbate liver injury and fibrosis and to develop therapies that can prevent or slow liver scarring. This is particularly true for NAFLD, a disease which affects up to 30% of the adult population and is now a major cause of the premature illness and death, but for which there is still no established drug therapy.

Our group conducts translational research investigating the pathophysiology of liver fibrosis/cirrhosis and hepatocellular cancer using a number of animal models of liver disease. These animal models include dietary models such as short-term methionine and choline deficient (MCD) and long-term high fat high cholesterol (HFHC) models which produce pathological lesions similar to those that can be seen in patients with NAFLD/NASH. Our biliary fibrosis models include short-term bile duct ligation (BDL) and long-term model of Mdr2-KO mice. In addition, we have also developed a number of perfusion models such as liver perfusion model and mesenteric vascular perfusion model to study hyperdynamic splanchnic circulation that develops from hemodynamic changes associated with activated systemic as well as local renin angiotensin system (RAS) in cirrhosis. We are also using a number of mouse liver-cancer models to study the potential of therapies we developed. The translational studies in humanized mouse models have been designed to test various therapies before we commence our human studies in patients with liver disease.

Our studies will significantly improve understanding of the role of the RAS and advanced glycation end products (AGEs) in liver disease and the potential impact of modulation of these pathways on hepatic fibrogenesis, mesenteric hemodynamics and portal hypertension. Importantly, these studies are largely translational. They include therapies that have been successfully applied in other human diseases, including selective tissue upregulation of a specific gene, and are therefore likely to have a major impact on the treatment of human liver disease.

Staff

• Professor Peter Angus, Medical Director of Victorian Liver Transplant Unit
• Dr Chandana Herath, Honorary Senior Research Fellow,
• Dr Adam Testro, Gastroenterologist & Honorary Fellow, Melbourne Clinical School
• Dr Christopher Leung, Gastroenterologist, Department of Gastroenterology, Austin Health, Clinical Lead, Melbourne Clinical School
• Dr Indu Rajapaksha, Research Officer
• Dr Lakmie Gunarathne, Research Officer

Collaborators

• Professor Ian Alexander, Childrens Hospital Westmead, University of Sydney
• Professor Josephine Forbes, Glycation & Diabetes Complications, Mater Research, University of Queensland
• Professor John Furness, Department of Anatomy & Neuroscience, The University of Melbourne
• Associate Professor Sof Andrikopoulos, Department of Medicine, Austin Health, The University of Melbourne
• Associate Professor Alexandra Sharland, Department of Surgery, Central Clinical School, University of Sydney
• Professor Jonel Trebicka, Department of Internal Medicine, University of Bonn, Germany
• Professor Missaka Wijayagunawardane, Department of Animal Science, University of Peradeniya, Sri Lanka
• Associate Professor Keerthi Siri Guruge, National Institute of Animal Health, Tsukuba, Japan
• Dr Anthony Zulli, College of Health and Biomedicine, Victoria University
• Dr Harinda Rajapaksha, LaTrobe University

Funding

• NHMRC project grant: Novel therapies targeting the alternate renin angiotensin system in chronic liver disease (2017-2021).