Liver & MetabolicStorr Liver UnitThe Storr Liver Unit studies liver function in both healthand disease states as well as the impact of liver diseaseson human health. We investigate better ways to preventor cure liver disease, aim to define the clinicopathologicaland genetic factors that predispose a person to liverinjury and liver cancer and determine how complicationscan be detected early to improve adverse clinicaloutcomes. The Unit is at the forefront of internationalclinical trials that seek to identify new therapies for thetreatment of liver disorders.
Throughout <strong>2005</strong> Professor Geoffrey Farrell has been onsabbatical with Professor Nelson Fausto, Department of Pathology,University of Washington, performing studies on geneticsusceptibility to carcinogen-induced liver cancer in mice and itsrelationship to aspects of hepatic lipid turnover. At WMI, ProfessorFarrell’s group continued to investigate how the processes ofoxidative stress, peroxisome proliferation-activated receptor gamma(PPAR gamma) and COX-2 activation modulate the development ofliver cancer. During <strong>2005</strong> Professor Farrell tendered his resignationand will leave WMI in early 2006. It is anticipated that a new StorrProfessor will be appointed by mid 2006.NHMRC Centre of Clinical ResearchExcellence in Liver DiseaseEstablished in 2003, the NHMRC Centre of Clinical ResearchExcellence (CCRE) to Improve Outcomes in Chronic Liver Diseaseconsists of several multifaceted projects including early detection(screening) and better management of liver cancer, nutritionalintervention in advanced liver disease, and nutritional, dietary andexercise intervention for patients with early stages of chronic liverdisease. During <strong>2005</strong>, we have continued to actively recruit patientsfor the various projects including a cancer screening program nowinvolving in excess of 220 patients at three Sydney hospitals, and alifestyle intervention study which has enrolled ~150 subjects. TheCCRE researchers have published papers during <strong>2005</strong> on thesubject of their research, and further publications are expected in2006, following analysis of the datasets.Molecular and cellular basis of liver diseaseIn recognition of an outstanding track record in research, the Unit,along with investigators at the Royal Prince Alfred Hospital wasawarded a prestigious NHMRC Program Grant (<strong>2005</strong>-2009) valuedat over $4 million to further study the molecular and cellular basis ofhuman liver diseases. Projects encompassed in the Programinclude studies on the pathological basis of non-alcoholicsteatohepatitis, which is the most common cause of liver damagein Western society, chronic hepatitis C, hepatic fibrosis andcirrhosis, autoimmune hepatitis and ischaemia-reperfusion injury.The core investigators have since established highly focusedresearch groups to conduct the studies outlined in the proposal.The Unit was also successful in obtaining two further NHMRCproject grants for 2006 to conduct research into genetic studies ofhepatitis C disease progression and on liver injury.Molecular PharmacologyThe focus of the Molecular Pharmacology Laboratory is toinvestigate the regulation of genes within the liver involved in themetabolism or breakdown of therapeutic drugs as well as toxicsubstances produced within the body, such as bile acids.The research has already produced outcomes that are havingsignificant impact on healthcare. Work on the mechanisms bywhich some drugs cause the metabolism of other drugs to beaccelerated, causing drug-drug interactions, has led to moreeffective tests to detect such unwanted properties early in the drugdevelopment process. Several patents, some of which have alreadybeen licensed to industry, now cover the applications of this work.An exciting extension of this work is to understand how drugs aremetabolised in the brain, which is the target organ for approximatelyone-third of all drugs (e.g. anti-depressants, anti-psychotics,analgesics), a process that presently is poorly understood.Recent work on bile acid metabolism and elimination has lead todiscoveries that are likely to result in improved therapies for patientswith liver diseases in which the flow of bile is obstructed (cholestaticliver diseases). In addition to two existing NHMRC project grants,this group has now received further funding from the NHMRC toprogress this work to the implementation of new therapies for suchpatients that will prevent or retard cholestatic liver injury that oftenresults in the development of cirrhosis. This work will be performedin collaboration with the laboratory of Prof Ron Evans at the Salk<strong>Institute</strong> and Prof Antoine Hadengue, Geneva University Hospitals.Portions of this work have recently been published in the form oftwo papers in the highly prestigious Proceedings of the NationalAcademy of Sciences, USA.An exciting area of research is determining why patients withadvanced cancer not involving the liver have impaired drugmetabolism by the liver, which results in life-threatening toxicity fromsome anti-cancer drugs. Work performed in collaboration with theCancer Centre at Concord Hospital is determining why thishappens and utilizing novel humanized transgenic mouse modelscreated at the WMI, we are developing therapies to counteract thisserious problem.
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