Cholestasis And Hepatocyte Injury In Chronic Liver Disease
Funder
National Health and Medical Research Council
Funding Amount
$615,967.00
Summary
The aim of this project is to understand the consequences of long-term cholestasis or impaired bile excretion/flow on normal liver cells (hepatocytes) and to test whether specific bile acids can cause irreversible damage to hepatocytes leading to their transformation into pre-malignant cells and hepatocellular carcinoma (primary liver cancer). The results from this project will inform new strategies in screening, prevention and treatment of liver cancer in children and adults with cholestasis.
Understanding The Role Of Sugar Metabolism In Liver Tumour Growth
Funder
National Health and Medical Research Council
Funding Amount
$631,979.00
Summary
Primary liver cancer is a deadly disease with limited chemotherapeutic options. The investigators of this proposal have recently determined that sugar intake (but not fat or complex carbohydrate) is a dominant driver of liver tumour growth in mice. The current proposal will investigate the specific contributions of glucose versus fructose in tumour burden, and determine whether blocking the conversion of sugars to fat in the liver represents a therapeutic strategy to block tumour growth in mice.
The Hippo/Yap Pathway Reprograms Glucose Metabolism To Fuel Tissue Growth.
Funder
National Health and Medical Research Council
Funding Amount
$659,105.00
Summary
Liver disease is a common cause of sickness and death in Australia. While factors critical to liver function are known, the cellular networks responsible for causing liver cancer are largely undefined. Our studies will use zebrafish as a model to study how the circuit known as the Hippo pathway reprograms metabolism to promote liver cancer. These studies will enhance our understanding how metabolism regulates liver growth and identify therapeutic targets to combat liver cancer.
Characterization Of ARL6IP5 In Hepatitis C-related Liver Cancer
Funder
National Health and Medical Research Council
Funding Amount
$505,283.00
Summary
The incidence and mortality from liver cancer is increasing rapidly in Australia, and hepatitis C virus infection is the most common cause. How hepatitis C leads to liver cancer is largely unknown. We identified a novel gene termed ARL6IP5 that appears to be specifically increased in liver tissue by chronic hepatitis C infection. In this project we will characterize the involvement and role of this gene in liver cancer development. Knowledge gained from this study will help us understand how hep ....The incidence and mortality from liver cancer is increasing rapidly in Australia, and hepatitis C virus infection is the most common cause. How hepatitis C leads to liver cancer is largely unknown. We identified a novel gene termed ARL6IP5 that appears to be specifically increased in liver tissue by chronic hepatitis C infection. In this project we will characterize the involvement and role of this gene in liver cancer development. Knowledge gained from this study will help us understand how hepatitis C leads to cancer.Read moreRead less
Detection Of Liver And Renal Function Abnormalities In The Australian & New Zealand Population Of Fontan Patients
Funder
National Health and Medical Research Council
Funding Amount
$345,080.00
Summary
Children born with complex heart defects and only one pumping chamber can now live into adulthood with an operation called the Fontan procedure. As this operation has only existed for 40 years, the long-term expectations for these children and young adults are still unclear, and their population is growing every year. There is now evidence that they may suffer from liver and kidney failure. This project will identify the severity of liver and kidney damage in our population of Fontan patients.
Advanced Imaging To Define Hepatic & Intestinal Drug Disposition In Aging & Liver Diseases
Funder
National Health and Medical Research Council
Funding Amount
$762,123.00
Summary
Aged people and liver disease patients have impaired drug absorption and elimination functions. Their response to drugs varies widely when given drug dosage regimens recommended for normal patients. This project will explore the possibility of using in vivo imaging techniques to define the gut and liver function and their response to administered drugs. This grant will help the selection of appropriate drugs and doses for aged people and patients with liver diseases, i.e. personalised medicine.
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
Visualisation And Early Prediction Of ROS-mediated Treatment Response In Liver Cancer By A Novel Nanoplatform
Funder
National Health and Medical Research Council
Funding Amount
$334,224.00
Summary
Change of tumour microenvironment has potential to serve as an early predictor of drug efficacy. This proposed project aims to develop a new technology to accurately measure tumour microenvironment during treatment, and to explore the correlation between this potential predicator and tumour growth. This technology would significantly improve the patient prognosis by revealing non-response to chemotherapeutics early and allowing the timely administration of alternative therapies.
Significance Of Microparticles In The Pathogenesis Of Liver Ischemia Reperfusion Injury
Funder
National Health and Medical Research Council
Funding Amount
$643,958.00
Summary
The overall aim of the project is to investigate the significance of microparticles in liver ischemia reperfusion injury (IRI). IRI causes damage to donor livers stored in preparation for liver transplantation. We postulate that microparticles released from the liver are critical in this form of injury. The expected outcomes are novel insights into liver IRI with the aim of developing new approaches to prevent liver damage during liver surgery, transplantation and shock.
Novel Early Detection Strategy For Liver Cancer Using Hepatitis B Splice Variants To Expediate Diagnosis And Improve Treatment Outcome
Funder
National Health and Medical Research Council
Funding Amount
$943,566.00
Summary
Hepatitis B virus (HBV) causes liver cancer, which is one of the only cancers that is increasing in prevalence. We have shown that smaller versions of HBV, termed splice variants, are even more strongly associated with liver cancer- people with higher levels of the splice variants were over 3 times more likely to have liver cancer. We will find out why, by thoroughly studying how the splice variants alter the virus and the host cell to promote liver cancer.