The Role Of MBOAT7 In Hepatic Inflammation: Implications For Therapy
Funder
National Health and Medical Research Council
Funding Amount
$848,340.00
Summary
When a fatty liver progresses to develop inflammation, patients are at-risk of liver-related morbidity and death. Currently, there are no effective therapies. From human studies, we have discovered that a lipid modifying enzyme (MBOAT7) profoundly regulates liver inflammation. In this proposal, we will obtain a detailed understanding of how the activity of this pathway modulates inflammation. We expect to show that MBOAT7 is a novel ‘druggable’ pathway for the treatment of liver inflammation.
The Epidemiology And Burden Of Liver Disease In Australia With An Emphasis On Non-alcoholic Fatty Liver Disease.
Funder
National Health and Medical Research Council
Funding Amount
$151,143.00
Summary
Non alcoholic fatty liver disease is now the commonest cause of abnormal liver function in Australia due to its close association with the obesity epidemic. It is likely to become the leading cause of liver failure and liver cancer over the next few decades. Despite this, the prevalence in Australian populations is unknown. The aim of this project is to assess how common this disorder is, the burden it places on the healthcare system and the effectiveness of treatment for liver cancer caused by ....Non alcoholic fatty liver disease is now the commonest cause of abnormal liver function in Australia due to its close association with the obesity epidemic. It is likely to become the leading cause of liver failure and liver cancer over the next few decades. Despite this, the prevalence in Australian populations is unknown. The aim of this project is to assess how common this disorder is, the burden it places on the healthcare system and the effectiveness of treatment for liver cancer caused by advanced non alcoholic fatty liver disease.Read moreRead less
Manganese is an essential trace element for normal health. However in some medical conditions manganese can build up in the brain and cause a Parkinson's like disease called manganism. Experimental evidence suggests that the liver plays an important role in the development of manganism and this project aims to explore the way the liver handles manganese in health and disease. These studies may assist in understanding how manganism develops.
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.
P53 And Hepatocyte Proliferation In Chronic Liver Disease
Funder
National Health and Medical Research Council
Funding Amount
$331,360.00
Summary
The aim of this project is understand how loss of control of p53, a tumour suppressor gene, in liver cells causes the transformation of normal liver cell (hepatocyte) to ‘rouge’ pre-cancerous cells in hepatocellular carcinoma (HCC) or primary liver cancer. We will test novel therapies to restore p53 function in liver cells in order to prevent or retard the development of HCC in patients with cirrhosis and those ‘at risk’ of this rapidly increasing fatal cancer in Australia.
MERTK Receptor Tyrosine Kinase: A Novel Therapeutic Target For Liver Fibrosis
Funder
National Health and Medical Research Council
Funding Amount
$870,972.00
Summary
Hepatic fibrosis is the principal cause of liver-related morbidity and mortality, for which there are no effective therapies. Thus, there is an urgent and unmet need to identify new targets to treat liver fibrosis. We have demonstrated for the first time, that liver fibrosis correlates with elevated hepatic expression of MERTK, a receptor tyrosine kinase. This project will explore whether MERTK function can be exploited to target and reverse liver fibrosis
DPP4 Family Proteases As Drivers Of Chronic Liver Injury
Funder
National Health and Medical Research Council
Funding Amount
$730,041.00
Summary
Type 2 diabetes afflicts over 220 million people and often causes a chronic liver injury. That and hepatitis viruses can cause cirrhosis, liver failure and liver cancer, which is the 2nd most common cause of cancer death. Many Australians suffer from diabetes, fatty liver and/or hepatitis virus infection. We will understand these diseases far better and likely discover a new therapy by assessing roles of the DPP4 family of enzymes in diabetes, fibrosis and fatty liver.
Targeting The Crosstalk Between Metabolism And Epigenetics To Treat Liver Fibrosis
Funder
National Health and Medical Research Council
Funding Amount
$1,032,259.00
Summary
Virtually all liver disease related morbidity and mortality is a consequence of fibrosis that culminates in liver failure or liver cancer. Since anti-fibrotic drugs are not available, new approaches to drug development are required. We have discovered a novel strategy for such drug development by modifying the expression of a specific gene (RARRES1) in a highly targeted manner and thereby interrupting the energy production that is needed by cells to drive fibrosis.
How Does Dietary Cholesterol Induce Non-alcoholic Steatohepatitis?
Funder
National Health and Medical Research Council
Funding Amount
$802,600.00
Summary
Non-alcoholic fatty liver disease is the most common liver disease that can progress to non-alcoholic steatohepatitis (NASH), cirrhosis and liver cancer. Dietary cholesterol is a major risk factor for NASH. We can demonstrate that cholesterol changes the gut bacteria. These bacteria generate toxic chemicals (bile acids) that signal to the liver and induce NASH. In this project, we use novel ways to clarify the mechanisms of liver inflammation and test novel therapeutic approaches to reverse it.
Effect Of Liver Pathophysiology On Hepatic Pharmacokinetics
Funder
National Health and Medical Research Council
Funding Amount
$457,500.00
Summary
The liver is the main organ in the body for the metabolism and biliary excretion of natural and foreign solutes. Various liver diseases such as cirrhosis, alcoholic liver disease, diet and drug induced fatty livers can affect the uptake and metabolism of drugs and their suitability- dosing needs. Some liver diseases such as fatty livers are very common but how rapidly drugs are metabolised in these patients is not well described. The work is important as it may help us better design new drugs an ....The liver is the main organ in the body for the metabolism and biliary excretion of natural and foreign solutes. Various liver diseases such as cirrhosis, alcoholic liver disease, diet and drug induced fatty livers can affect the uptake and metabolism of drugs and their suitability- dosing needs. Some liver diseases such as fatty livers are very common but how rapidly drugs are metabolised in these patients is not well described. The work is important as it may help us better design new drugs and better choose which drugs to give and, if so, in what doses. In addition, many liver diseases require a biopsy for a definite diagnosis of the likely function of the liver. Estimation of liver function is particularly important in estimating whether there will be sufficient reserve on resection of a cancer or deciding if a liver transplant is needed. The liver is also a very complex organ which can trap or breakdown solutes by a range of different systems. Also of importance is how those diseases affect drug disposition in the liver given that an altered hepatic drug disposition may affect systemic response to the drugs and their metabolites. This work seeks to answer these questions.Read moreRead less