Committed to Research

Liver Immunology

General Practice

The Liver Immunology Research Unit aims to better understand the influence of lifestyle, chronic disease and infection on the hepatic immune system. From clearance of viral infection as is the case with Hepatitis C virus, to the development of severe inflammation and fibrosis due to fatty liver disease, the hepatic immune system possesses both beneficial and damaging roles. Our research focus lies within the innate arm of the immune system, with a specific emphasis on how natural killer (NK) cells and liver macrophages (Kupffer cells) mediate these effects. Our unit is currently located at both the Blacktown Clinical School and Research Centre, Blacktown Hospital, as well as the Westmead Institute for Medical Research, Westmead Hospital. To accomplish our basic research goals, we utilise a number of advanced laboratory techniques including flow cytometry, fluorescence microscopy, genomics and transcriptomics (RNA sequencing), as well as cell culture approaches that include primary cell isolation and organoid culture. We collaborate extensively with external research groups and hospital staff to obtain tissue and blood specimens used for analytical measurements and primary cultures.

Our People

Liver Immunology Unit Heads
Prof Golo Ahlenstiel, Dr Scott Read
PhD Student – Dr Ratna Wijaya

 

Ongoing projects and student opportunities

  1. “Development of organoid culture systems”
    Organoids are three dimensional structures grown in vitro from primary tissue that retain the characteristics of their primary source, including self-renewal, organisation, and differentiation. As such, they are an optimal model to study the influence of genetic and environmental factors on disease progression and treatment. Using in vitro co-culture systems, this project will examine the factors that contribute to “leaky gut” in NASH, and how translocating microbes influence liver inflammation. In addition to enteric bacterial, fungal and human viruses, this project contains a unique focus on bacteriophages, and their contribution to chronic immune stimulation in both the gut and liver. This study utilises cutting edge primary cell culture, flow cytometry and molecular biology techniques to discover unknown connections between gut and liver immunity, and will enable a better understanding of inter-organ interactions that contribute to NASH pathogenesis.
  2. “The role of interferon lambda in liver inflammation and fibrosis”
    Interferon lambda (IFN-λ) is a central antiviral cytokine in the liver that is elevated in NASH, and that contributes to the progression of liver inflammation and fibrosis. The mechanism of IFN-λ induction, and cells involved however, remain unknown. We hypothesise that microbial ligands originating from the gut, enter the liver in the portal blood and stimulate IFN-λ expression. This project aims to determine the contribution and identity of intestinal biota that stimulate IFN-λ, the responsive cells, and the mechanisms by which IFN-λ drives liver inflammation. We will utilise cutting edge genomics, primary cell culture, flow cytometry and molecular biology techniques to shed some light on the role of IFN-λ in NASH. This study will pave the way for future treatments aimed at halting the progression of inflammation in NASH.
  3. “Immune dysregulation in obesity”
    Obesity is associated with alterations in metabolism, immune function, inflammation and microbiome, however the inter-relationship between these factors remains ill-defined. Blacktown Public Hospital has recently implemented a large healthy weight and bariatric surgical program, which provides the ideal environment to address the poorly understood, but essential aspect of obesity. Samples obtained pre- and post-bariatric surgery will be used to understand how obesity and metabolic syndrome cause immune dysregulation promoting subsequent development of obesity related complications in liver, gut and cardiovascular system. This project will examine the effects of bariatric surgery and subsequent weight loss on systemic, as well as liver and intestinal immune activity and dysregulation. In particular, how rapid weight loss alleviates chronic inflammation and immune exhaustion associated with obesity. Changes in microbiome and intestinal permeability will also be examined with respect to liver inflammation and immunopathology. This project will possess a strong clinical and translational focus, relating immune parameters to clinical outcomes. In vitro analysis of immune cell phenotypes will be performed by flow cytometry, RNAseq and primary liver and intestinal cell culture will be used to elucidate pathological mechanisms.

 

Current collaborators

Jacob George (University of Sydney, Westmead Institute for Medical Research), Andrew Harman (Westmead Institute for Medical Research), Dr Grahame Ctercteko & Dr Martijn Gosselink (Colorectal Surgery, Westmead Hospital), Vincent Lam (Upper Gastrointestinal Surgery, Westmead Hospital), Meredith O’Keeffe (Monash University), Carola Venturini & John Iredell (Westmead Institute for Medical Research), Nick King & Helen McGuire (Charles Perkins Centre), John Sebastian Eden (University of Sydney), Patrick Bertolino (Centenary Institute), David Booth (Westmead Institute for Medical Research), Jonel Trebicka (University of Bonn), Andrew Lloyd (University of New South Wales)


Contact: Dr Scott Read.

 

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