About Professor Jacob George

Professor George undertakes basic research on non-alcoholic steatohepatitis (NASH) and hepatic fibrosis. He is also researching the molecular and cellular basis for disease progression in chronic hepatitis C. He has published seminal papers on the central role of transforming growth factor beta (TGF beta) in fibrogenesis.

Professor George is the Robert W Storr Chair of Hepatic Medicine and Professor of Gastroenterology and Hepatic Medicine, Storr Liver Unit, Westmead Millennium Institute, University of Sydney. He is also Head of the Department of Gastroenterology and Hepatology at Westmead Hospital and Postgraduate Coordinator for the Western Clinical School.

Professor Jacob George graduated MBBS from the University of Queensland (University Medal) in 1984. He trained in Gastroenterology and Hepatology at the Royal Brisbane Hospital and undertook a PhD at the University of Sydney on cirrhosis and hepatic cytochrome P450 expression in man. He was the recipient of an NHMRC Neil Hamilton Fairley Fellowship (1995-1997) and undertook postdoctoral research at the University of California San Francisco. He received the American Liver Foundation Postdoctoral Research Fellowship (1996). In 1998, Professor George was appointed Senior Lecturer in Hepatology, Department of Medicine, University of Sydney at Westmead Hospital. In 2005 he was appointed Professor of Gastroenterology and Hepatic Medicine and Head of Gastroenterology and Hepatology at Westmead Hospital. He was appointed as the Robert W. Storr Chair of Hepatic Medicine at the University in 2006. Professor George is the Scientific Convenor for the Westmead Association Scientific Meeting in 2007 and is the Post Graduate Coordinator of the Western Clinical School of the University of Sydney. These topics are being explored within the Storr Liver Unit, Westmead Millennium Institute: 1. The Role of Leptin in Modulating Alcohol-Associated Hepatic fibrosis: An in vitro study This project will assess whether the hormone leptin, either directly and/or indirectly potentiates alcohol-induced liver injury and fibrosis. The studies outlined we anticipate will elucidate the mechanisms whereby overweight and obesity makes the liver more susceptible to alcohol-associated liver disease. We will employ hepatic stellate cells (HSCs), Kupffer cells (KCs) and sinusoidal endothelial cells (SECs) isolated from both normal and Zucker rats (leptin receptor deficient) to determine whether combined treatment with leptin and alcohol (or acetaldehyde) directly and/or indirectly promotes alcohol-induced expression by HSCs of scar tissue components (Collagen I), or of mediators that are well known to drive the production of scar tissue.  The relevant intracellular pathways involved in mediating these effects will be analyzed. Zucker rats will be used to clarify whether any observed effects are mediated by the leptin receptor. 2. The role of leptin in the pathogenesis of portal hypertension and cardiomyopathy in rats with liver cirrhosis This project seeks to determine whether exogenous leptin administration leads to systemic or splanchnic (gut) hemodynamic changes in normal rats and in those with liver injury. We will also determine if exogenous leptin administration modulates cardiac function (e.g. induction of cardiac hypertrophy and cirrhotic cardiomyopathy) and portal hemodynamics. Three rat models of either liver fibrosis and/or portal hypertension (Bile duct liagtion, carbon tertrachloride injection and portal vein partially ligation) will be studied. The systemic and splanchnic hemodynamic effects of leptin on mean arterial pressure, blood flow in the portal vein and splenorenal vessels as well as portal pressure will be measured. In addition, cardiac function such as cardiac output, systolic and diastolic pressure, heart rate, left ventricular pressure and dp/dt will be assessed. 3. Protein microarray of hepatic stellate cells The drawbacks of cDNA microarrays are that they might underestimate post-transcriptional and post-translational effects. As a result, protein microarrays and/or functional proteomics have emerged as an attractive technology for studying disease mechanisms including liver fibrosis. Since hepatic stellate cells are the principal cell source of excessive extracellular matrix proteins during liver fibrosis, protein microarray analysis of hepatic stellate cells promises to be a novel and important method to develop a comprehensive understanding of the molecular basis of liver fibrosis. We will use protein mi

Selected publications

For a comprehensive list of Professor George's publicatons, please visit his Sydney Medical School profile page.