Research Opportunities

Hepatitis B virus (HBV) transmission is usually prevented by infant vaccination. Anti-viral therapy in some settings is beneficial to increase protection. The optimal regimens during pregnancy and post-partum are the subject of this work.

South Western Sydney has a vast migrant population where English is not the primary language spoken at home. Health literacy is important for patients to understand their disease and treatment options. This project will devise and novel strategies to improve health literacy in these culturally and linguistically diverse populations and examine their efficacy and utility.

Liver Cancer has a poor prognosis and often presents late in South Western Sydney, outside of screening programs. This project will investigate reason for late presentation and course of appropriate surveillance in SWSLHD.

Hepatitis C virus (HCV) is highly transmissible and particularly endemic within difficult to access populations. Despite the advent of antiviral medications that eliminate the virus in a majority of people, difficult to access populations face many social and logistical hurdles that impacts access to specialists and effective treatment. The goal of these projects is to widen the reach for HCV eradication.

• Project ECHO® - examining this novel mentoring programme to establish if healthcare outcomes in difficult to access populations can be improved.
  
  
• SEARCH (Screening Emergency Admissions for Rates of Chronic Hepatitis) – screening high risk populations (overseas born patients from countries with high prevalence of HBV and HCV, and Indigenous Australians) according to the NSW Health Testing Policy.

• Dried Blood Spot - aims to provide a means to screen ‘Difficult venous access patients/patients who are for whatever reason cannot be screened in the GP/OST providers setting and attending Project ECHO/and have a history of IVDU’ patients and to provide support to the ECHO participants to be able to identify both positive and negative patients for HIV/HCV and treat patients with HCV.

Shared decision making (SDM) in chronic diseases enables and encourages patients to play an active role in the management of their health. Decision Aids (DAs) are tools developed for preparing patients for decision making about specific treatment choices and are used to promote SDM. This project will identify and assess preferences, challenges, and quality of life in patients with ulcerative colitis.

Biologics are used in the management of IBD but a proportion of patients (up to 50%) will have exacerbation of their disease with standard dosing. This has been managed with empiric dose escalation and/or greater frequency of biologic administration. However, the advent of quantitative assays for biologic levels and anti-biologic antibodies (therapeutic drug monitoring) has made individualisation of biologic dosing possible. We have multiple projects investigating the utility and cost effectiveness of biologic therapeutic drug monitoring in IBD as well as the role of TDM in personalised care.

There are numerous support tools available for clinicians to educate them on IBD and treatment options. This project will assess and determine the usefulness of these tools in clinical practice.

Both Crohn’s disease and ulcerative colitis are characterised by a series of relapses and remissions, and there is no cure. Currently, there is limited understanding of the clinical, environmental and genetic factors that may play a role in determining disease severity. This project will investigate the molecular architecture of IBD phenotypes and sub-phenotypes, and the development of predictive tools for disease natural history and response to treatment.

Malnutrition and obesity are common in patients with IBD. Patients may have nutrient deficiencies or suffer from nutritional issues. There is evidence that nutrition and diet assessments and plans can induce disease remission and this project will further investigate this.

There are different treatments for IBD but minimal information on the uses of these therapies during pregnancy. This project will investigate the different IBD treatments given to pregnant women and assess their experiences and the outcomes of their therapy during their pregnancy.

In Australia, approximately 1 in 250 people aged between 5 and 49 years suffers from IBD. It is predicted that by 2022, there will be 100,000 people in Australia affected by IBD. Of these, over 5,000 patients with IBD will be in the South Western Sydney Local Health District (SWSLHD). This project will investigate factors affecting the epidemiology of IBD in SWSLHD.

The gut microbiome plays an important role in IBD. There is currently limited understanding about which aspects of the microbiome are important in IBD and furthermore, how we can use our knowledge of the microbiome to improve disease control. We have a number of projects investigating aspects of the microbiome and IBD.

Chronic liver disease (CLD) affects >600 million people and is a leading cause of human mortality and morbidity. Importantly, chronic inflammation is a pivotal driver of progressive fibrosis and eventual cirrhosis resulting in both liver failure and liver cancer. Current therapeutic options to treat CLD are limited and there are no effective anti-fibrotics used in clinical practice. Our unique approach will both diminish inflammation and reduce fibrosis by targeting a single multifunctional ‘druggable’ protein, basigin. We have abundant data demonstrating leukocyte aggregation within the liver with injury. This project will comprehensively describe and functionally characterise basigin-dependent leukocyte aggregation.

The GLL has adopted a gene discovery approach to identify novel liver injury associated pathogenic pathways. A key discovery from this approach was that basigin can determine the severity of intrahepatic injury. In progressive liver injury, we have shown and published that basigin can regulate hepatocyte matrix metalloproteinase expression, which if blocked by a monoclonal antibody, reduces liver fibrosis. This research project will develop novel therapeutics to target basigin.

Liver organoids can be utilised as an ex-vivo model of liver injury and liver cancer. They are established from resected liver tissue, expanded in 3D culture and differentiated into mature, functional hepatocytes for experiments. This project will establish patient-derived liver cancer organoids to enable us to develop algorithms that will allow individualised treatment of liver cancer patients. Importantly, this patient-derived liver cancer organoid platform enables the testing of current and novel therapies in a truly personalised “precision medicine” approach.

Hepatocellular carcinoma (HCC) is the fourth most common malignancy globally and is increasing in frequency. Due to early HCC being asymptomatic, diagnosis occurs late when only 20-25% of HCC patients can be offered curative treatments. Novel HCC biomarkers have been hampered by the heterogeneity of HCC subtypes.

Our recent discoveries may be the key to solving these problems. Firstly, we have analysed several publically-available whole exome sequencing datasets of HCC and paired non-tumour tissue. Our results have specifically identified deleterious passenger mutations (DPMs), which are mutations that decrease cell survival but are not driver mutations of HCC. We have found that HCC genomes contain significantly more DPMs than the paired non-tumour tissue, and DPMs are a potential novel biomarker for HCC risk. Further, we can isolate hepatocyte-specific microvesicles (MV) from serum, which contain quantifiable liver-derived miRNA and DNA. Therefore, we can profile miRNA and DPM to overcome the problems of HCC heterogeneity and develop a sensitive non-invasive test that is urgently needed.