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Harnessing Endogenous L1-mediated Mutagenesis To Elucidate New Candidate Genes For Liver Cancer
Funder
National Health and Medical Research Council
Funding Amount
$632,656.00
Summary
Retrotransposons are mobile genes that copy-and-paste themselves in our genome. Previously thought to represent “junk DNA”, retrotransposons are increasingly recognised to play major roles in biology. In a recent publication in Cell, we found that retrotransposons were highly active in some types of liver cancer, mutating key genes required to block tumour formation. In the current study, we will determine in greater depth how, and how often, these genes are involved in other types of liver canc ....Retrotransposons are mobile genes that copy-and-paste themselves in our genome. Previously thought to represent “junk DNA”, retrotransposons are increasingly recognised to play major roles in biology. In a recent publication in Cell, we found that retrotransposons were highly active in some types of liver cancer, mutating key genes required to block tumour formation. In the current study, we will determine in greater depth how, and how often, these genes are involved in other types of liver cancer.Read moreRead less
Development Of Serum Models That Can Predict Clinical Outcomes In Chronic Liver Disease
Funder
National Health and Medical Research Council
Funding Amount
$380,694.00
Summary
The overall objective of this project is to develop blood tests that can accurately predict liver related death, liver cancer and liver decompensation respectively for patients with chronic liver disease. Blood tests will also be developed to predict cardiovascular disease in patients with non-alcoholic fatty liver disease. Furthermore, we will evaluate the use of repeated blood tests to assess if this can more accurately predict death and complications compared to a single time point.
Hepatocellular Carcinoma: Understanding The Genotoxic Risks Of Liver-targeted Gene Therapy Using Recombinant AAV Vectors
Funder
National Health and Medical Research Council
Funding Amount
$891,639.00
Summary
Advances in gene transfer technology using an engineered virus known as AAV underpin success in the treatment of haemophila B, and offer the exciting prospect of treating many other liver diseases. While continued improvement of gene transfer efficiency is essential there is an equal need to focus on safety. We have discovered a genetic element in AAV that we believe is a key to unlocking accurate analysis of the safety of AAV-based gene transfer technology. Here we propose to turn the key.
Hepatocellular carcinoma (HCC), or liver cancer, is a major global problem. Most people present with advanced disease and current therapies are relatively ineffective. Small RNAs, called microRNAs are a new form of therapy that may present new options for patients with HCC. We have characterised a microRNA that is a powerful inhibitor of HCC growth both in cells and in preclinical animal models. This project will characterise the microRNA’s function in HCC and as a potential therapeutic.
There are ~1.6 billion overweight adults worldwide & this is predicted to rise to 2.3 billion by 2015. In Australia > 2/3 of adults are overweight or obese. Obesity is a key factor in the progression of many human malignancies. Obesity poses the greatest risk for the development hepatocellular carcinoma (HCC), a deadly cancer refractory to nearly all available anti-cancer therapies. This application will delineate the molecular mechanisms by which obesity promotes HCC development.
Skin cancer affects 60% of Australians. Nicotinamide (vitamin B3) prevents many of sunlight’s damaging effects and reduces premalignant keratoses by 35% compared to placebo in sun-damaged individuals. We now need to test whether nicotinamide can prevent skin cancer. Skin cancer patients will receive nicotinamide or placebo for 12 months and new cancers will be counted in each group. Nicotinamide is safe, widely available and an exciting opportunity for cost-effective skin cancer prevention.
Cancers of the skin are the most common tumours in humans, and their diagnosis and treatment impose the largest costs on Australia’s cancer budget. While much has been learned about the roles of sunlight and skin type as risk factors for skin cancer, relatively little is known about the genes conferring risk. This study will compare the genetic profiles of over 6000 patients with skin cancer to 3000 people without skin cancer to pinpoint the genes responsible for skin cancer.
HLA-G/H2-Bl Is Critical For Regulating Inflammation In The Liver
Funder
National Health and Medical Research Council
Funding Amount
$494,050.00
Summary
The key factor to induction of liver fibrosis, progression to cirrhosis, and hepatocellular carcinoma is inflammation. Liver transplant and liver regeneration following liver resection are also dramatically impaired by elevation of inflammation. We have identified a potent anti-inflammatory protein, HLA-G, that is critical for regulating post-surgical inflammation in the liver. We will determine if HLA-G can reverse and/or block liver fibrosis and modify HLA-G for improved clinical potential.
Bridging The GAPP Between The Laboratory And Clinic To Prevent Gastric Adenocarcinoma And Proximal Polyposis Of The Stomach (GAPPS).
Funder
National Health and Medical Research Council
Funding Amount
$724,877.00
Summary
Gastric Adenocarcinoma and Proximal Polyposis of the Stomach (GAPPS) is an inherited form of gastric cancer. Affected patients develop a large number of gastric polyps and are at risk of gastric cancer in their 30s. The only effective treatment is to surgically remove the stomach. Gastrectomy is, however, associated with significant post-operative complications. We will use laboratory and mouse models of GAPPS to identify acceptable new approaches to prevent cancer in these patients.
Establishment Of A Biomarker To Test Molecular Risk Of Gastric Cancer
Funder
National Health and Medical Research Council
Funding Amount
$834,448.00
Summary
Less than 20% of patients live 5 years after a diagnosis of gastric cancer (GC). This is due to the advanced stage at the time of diagnosis. We have no markers to monitor therapy of cancer. This proposal aims to use next generation sequencing to find specific genetic changes in a persons tumour that can be used to monitor therapy. We aim to use the same technology to group patients into high-risk or low risk for development of GC. This will allow specific screening only for those at high-risk.