1. Please give a summary of your research.
Chronic liver disease (CLD) has a huge clinical burden globally, affecting up to 30% of the population. Its major underlying causes are viral hepatitis, alcohol and non-alcoholic fatty liver disease (NAFLD). Irrespective of aetiology, CLD results in the development of liver fibrosis, or scarring of the liver. About 5.5 million Australians have NAFLD, a condition in which the liver accumulates fat, causing cell death, inflammation and aberrant wound healing responses that lead to fibrosis. NAFLD can progress to non-alcoholic steatohepatitis (NASH), which is associated with a range of serious sequelae such as liver cancer. Despite its growing prevalence, NAFLD remains largely undiagnosed as patients often have no symptoms. Furthermore, no approved therapies exist for the treatment of NAFLD/NASH, and thus there is an increasing demand for donor livers for transplant. New diagnostics and therapeutics for CLD are thus urgently needed.
My research aims to better understand molecular mechanisms of liver fibrosis. I have used an innovative combination of approaches to gain new insights into the roles that our genes play in the development and severity of CLD, including NAFLD. I profiled gene expression changes in liver biopsies of patients with different underlying causes of CLD and at various stages of liver fibrosis, in combination with analysis of specific markers in the blood that are predictive of liver fibrosis. This combined approach enabled me to identify a core set of liver fibrosis-associated genes, as well as a specific protein that drives the expression of multiple CLD-linked genes. Furthermore, by comparing the genetic profiles of CLD patients with and without fatty liver, I was able to pinpoint a set of genes specifically associated with fatty liver disease. The outcomes of this research offer potential for developing new biomarkers and therapeutic interventions to both treat this disease and halt its progression.
2. Please include any additional details you would like to share
As an early career post-doctoral researcher, I have established and led a completely new project within the Institute for Molecular Bioscience (IMB) Centre for Inflammation and Disease Research (CIDR) at The University of Queensland. This project, which focused on characterizing inflammation-associated determinants of chronic liver disease, represented a new research direction for the laboratory (Sweet laboratory) and institute (IMB) in which I am based. The project bridged clinical and basic research, and required me to co-ordinate with clinicians, patients and other researchers. Ultimately, the findings from this study enabled me to identify inflammation-related proteins as potential targets and biomarkers for liver fibrosis, and to identify a particular transcription factor as a key driver of fibrosis-associated genes. This research has opened up many new avenues for future pursuit, one of which is currently being pursued through an industry collaboration. The findings from this study were recently published (Ramnath et al, JCI insight, 2018; PMID: 30046009: https://insight.jci.org/articles/view/120274; see also: https://insight.jci.org/posts/80). As of 22nd August, this article was in the top ten most read articles in the last 30 days for all articles published in JCI Insight over the last 2 years.
An early career post-doctoral researcher, leading a project characterising inflammation-associated determinants of chronic liver disease at the Institute for Molecular Bioscience (IMB) Centre for I...