Alcohol biology and genetics

Alcohol biology and genetics of liver disease is an important area of research at ECC within the Alcoholic Liver Disease Research Program. The program, led by Clinical Professor Devanshi Seth, undertakes a range of clinical, fundamental and translational research. Our research is internationally recognised for significantly advancing the field by contributing to the understanding of genetics and molecular mechanisms of alcohol-related liver disease (ALD).

 

Clinical research: Our multinational GenomALC Consortium led by Seth is investigating the genetic/genomic factors associated with the risk of alcoholic cirrhosis across Australia, UK, USA and Europe. The team established the world’s largest biobank and database from ~6700 drinkers and identified novel genetic risks associated with alcohol-related cirrhosis. This ongoing research, funded by the National Institutes of Health (NIH)/National Institute on Alcohol Abuse & Alcoholism (NIAAA), USA, continues to explore the genetic architecture of this disease.

 

Fundamental research: This research focuses on understanding the molecular mechanism underlying progression of ALD using experimental models, including animal (mouse, zebrafish) models of fatty liver. Research using state-of-the-art gene-editing tools (Crispr-Cas9) in a zebrafish model of alcohol-induced fatty liver is underway studying the mechanisms of action of the genes (identified through GenomALC findings) involved in lipid (fat) metabolism.

 

Translational research: (i) The GenomALC study developed a novel genetic risk score (GRS) and combined with clinical risk (diabetes) developed a predictive model to identify patients at higher risk of cirrhosis. This novel concept is now the being planned for a randomized clinical trial that underpins the implementation of this research with a potential to significantly impact the field of genomics and personalised medicine for ALD patients. (ii) PETH test, a semi-quantitative measure for alcohol use, was established by Prof Seth’s research group at RPA Hospital. This test is now routinely used in clinical settings by Drug Health and Liver clinics to determine alcohol use, changing the management of Alcohol Use Disorder (AUD) patients and used in clinical trials to evaluate alcohol addiction treatment.