Alcoholic Liver Disease Program
Alcoholic liver disease has the highest mortality amongst all alcohol related disorders and needs further research. There is no effective treatment for this debilitating hidden epidemic. The overall goal of this research is to understand the mechanisms of how alcohol injures the liver and identify potential genetic/non-genetic bio-markers for therapy and diagnosis. Dr Seth’s research program addresses the following clinical and fundamental issues for better understanding of this disease leading to improved patient care.
Why do only some drinkers get cirrhosis while others who drink similar levels do not? To answer one of the big questions in this field Dr Seth leads a NIH/NIAAA (USA) funded multinational GenomALC Consortium. The focus of the consortium is to explore genome wide genetic and epigenetic factors that predispose some drinkers to and protect others from developing ALD. This program has created one of the largest biobank and clinical database of thousands of heavy chronic drinkers with great potential for future studies.
Establishing blood biomarkers of alcohol consumption and alcoholic liver disease. Current markers for alcohol consumption and self-report are sub-optimal and unreliable. Seth and her team have established tests using UHPLC-MS/MS (Clinical Pathology, RPAH) for measuring direct metabolites of alcohol (PEth, EtG and EtS) as serum biomarkers for alcohol consumption. Development of and access to these tests will significantly improve the screening and monitoring of alcohol use in individuals with alcohol-related problems, such as addiction, pre- and post-liver transplant, alcohol dependence treatment and in other non-clinical settings (social services, workplace, prison, driving, judicial, forensics, court disputes).
Understanding the cellular/molecular mechanisms of alcohol-induced liver injury and liver regeneration. (i) Seth laboratory has established in vitro and in vivo models of alcohol and alcohol plus high fat diet to study mechanisms of liver injury. In particular, role of Osteopontin (first reported in ALD by Seth) in fibrogenesis. (ii) The group has identified rare circulating endothelial progenitor cells (EPCs) altered with alcohol in human and mice that may have a role in angiogenesis mediated liver regeneration during injury. (iii) Another large international project is to identify microRNAs (miRNAs) as novel diagnostic markers in liver and kidney toxicity due to prescription drugs (e.g. paracetamol) and poisoning (e.g. pesticides, snakebite).
Australian
Edith Collins Centre Drug Health Services, Sydney Local Health District
QIMR Berghofer Medical Research Institute
Royal Prince Alfred Hospital
University of Newcastle
University of Sydney
International
Assistance Publique Hopitaux Paris (APHP), France
Center for Liver Diseases, University of Pittsburgh Medical Center, USA
CHU de Montpellier, France
CHU de Nimes, France
CHU Lille, France
CHU Rennes, France
Clinique d’Hépatologie Brussels, Belgium
Department of Medical and Molecular Genetics, Indiana University, USA
Department of Metabolism, Digestion and Reproduction, Imperial College London, UK
Hôpital Antoine-Béclère, France
Hopital Universitaire Antoine Beclere (APHP), France
Hôpital Universitaire Caremeau, France
Hopital Universitaire Jean Verdier (APHP), France
Hopital Universitaire Pitie Salpetriere (APHP), France
Indiana University, USA
Institut National de la Sante Et de la Recherche Medicale (Inserm), France
Institute for Liver & Digestive Health, Imperial College, UK
Institute of Liver Biliary Sciences (ILBS), India
L’hôpital Universitaire Carémeau, France
Lerner Research Institute, USA
Molecular Psychiatry Laboratory, University College London, UK
MRC Centre for Drug Safety Science and Liverpool Centre for Alcohol Research, University of Liverpool, UK
Newcastle Freeman Hospital, UK
Newcastle University, UK
Newcastle Upon Tyne Hospital, UK
NIH National Institute on Alcohol Abuse Alcoholism (NIAAA), USA
Nottingham University Hospital, UK
Privatklin Meiringen, Switzerland
Psychiatry Hospital University Munich, Germany
Purdue University, USA
Salem Medical Center, USA
Service Addictologie CHRU Carémeau, France
Sorbonne Universite, France
Technical University of Munich, Germany
Translational Genomics Group, Inflammatory Bowel & Immunobiology Research Institute, USA
UCL Institute for Liver & Digestive Health, Division of Medicine, University College London, UK
Universite de Montpellier, France
Universite de Rennes 1, France
Université Libre de Bruxelles, Belgium
University Hospital Zurich, Switzerland
University of California, USA
University of Liverpool, UK
University of North Carolina, USA
University of Nottingham, UK
University of Sheffield, UK
University of Zurich, Switzerland
US Department of Veterans Affairs, USA
VA Long Beach Healthcare System, USA
Why do only some drinkers get cirrhosis while others who drink similar levels do not? To answer one of the big questions in this field Dr Seth leads a NIH/NIAAA (USA) funded multinational GenomALC Consortium. The focus of the consortium is to explore genome wide genetic and epigenetic factors that predispose some drinkers to and protect others from developing ALD. This program has created one of the largest biobank and clinical database of thousands of heavy chronic drinkers with great potential for future studies.
Establishing blood biomarkers of alcohol consumption and alcoholic liver disease. Current markers for alcohol consumption and self-report are sub-optimal and unreliable. Seth and her team have established tests using UHPLC-MS/MS (Clinical Pathology, RPAH) for measuring direct metabolites of alcohol (PEth, EtG and EtS) as serum biomarkers for alcohol consumption. Development of and access to these tests will significantly improve the screening and monitoring of alcohol use in individuals with alcohol-related problems, such as addiction, pre- and post-liver transplant, alcohol dependence treatment and in other non-clinical settings (social services, workplace, prison, driving, judicial, forensics, court disputes).
Understanding the cellular/molecular mechanisms of alcohol-induced liver injury and liver regeneration. (i) Seth laboratory has established in vitro and in vivo models of alcohol and alcohol plus high fat diet to study mechanisms of liver injury. In particular, role of Osteopontin (first reported in ALD by Seth) in fibrogenesis. (ii) The group has identified rare circulating endothelial progenitor cells (EPCs) altered with alcohol in human and mice that may have a role in angiogenesis mediated liver regeneration during injury. (iii) Another large international project is to identify microRNAs (miRNAs) as novel diagnostic markers in liver and kidney toxicity due to prescription drugs (e.g. paracetamol) and poisoning (e.g. pesticides, snakebite).
Australian
Edith Collins Centre Drug Health Services, Sydney Local Health District
QIMR Berghofer Medical Research Institute
Royal Prince Alfred Hospital
University of Newcastle
University of Sydney
International
Assistance Publique Hopitaux Paris (APHP), France
Center for Liver Diseases, University of Pittsburgh Medical Center, USA
CHU de Montpellier, France
CHU de Nimes, France
CHU Lille, France
CHU Rennes, France
Clinique d’Hépatologie Brussels, Belgium
Department of Medical and Molecular Genetics, Indiana University, USA
Department of Metabolism, Digestion and Reproduction, Imperial College London, UK
Hôpital Antoine-Béclère, France
Hopital Universitaire Antoine Beclere (APHP), France
Hôpital Universitaire Caremeau, France
Hopital Universitaire Jean Verdier (APHP), France
Hopital Universitaire Pitie Salpetriere (APHP), France
Indiana University, USA
Institut National de la Sante Et de la Recherche Medicale (Inserm), France
Institute for Liver & Digestive Health, Imperial College, UK
Institute of Liver Biliary Sciences (ILBS), India
L’hôpital Universitaire Carémeau, France
Lerner Research Institute, USA
Molecular Psychiatry Laboratory, University College London, UK
MRC Centre for Drug Safety Science and Liverpool Centre for Alcohol Research, University of Liverpool, UK
Newcastle Freeman Hospital, UK
Newcastle University, UK
Newcastle Upon Tyne Hospital, UK
NIH National Institute on Alcohol Abuse Alcoholism (NIAAA), USA
Nottingham University Hospital, UK
Privatklin Meiringen, Switzerland
Psychiatry Hospital University Munich, Germany
Purdue University, USA
Salem Medical Center, USA
Service Addictologie CHRU Carémeau, France
Sorbonne Universite, France
Technical University of Munich, Germany
Translational Genomics Group, Inflammatory Bowel & Immunobiology Research Institute, USA
UCL Institute for Liver & Digestive Health, Division of Medicine, University College London, UK
Universite de Montpellier, France
Universite de Rennes 1, France
Université Libre de Bruxelles, Belgium
University Hospital Zurich, Switzerland
University of California, USA
University of Liverpool, UK
University of North Carolina, USA
University of Nottingham, UK
University of Sheffield, UK
University of Zurich, Switzerland
US Department of Veterans Affairs, USA
VA Long Beach Healthcare System, USA
