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.
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.
Delineating The Clinical And Molecular Heterogeneity Of Fatty Liver Disease To Inform Treatment
Funder
National Health and Medical Research Council
Funding Amount
$1,731,372.00
Summary
Fatty liver disease from excess weight affects 1 in 3 adult Australians. The disease has no treatments and many patients develop liver failure or liver cancer. Clinically, the disease is characterized by marked heterogeneity, a challenge for developing biomarkers and treatments. To move towards precision medicine, this project will undertake an inter-disciplinary program that embraces disease complexity and integrates environmental and genetic risk with the power of mathematical modelling.
NAFLD, NASH And Hepatocellular Carcinoma: Mechanisms & Potential Treatments
Funder
National Health and Medical Research Council
Funding Amount
$692,992.00
Summary
Liver cancer is one of the most common and fatal cancers world-wide. In developed countries, the past three decades has seen its incidence treble becoming the fastest rising cause of cancer deaths. In some patients liver cancer seems to be caused by obesity. The reason why some obese patients get liver cancer and others do not is unknown. In addition, there are few treatment options. In these studies we will research what causes liver cancer in obesity and test two new potential therapies.
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.
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
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.
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.
Protecting Fatty Livers From Hepatic Ischemia-reperfusion Injury In Liver Surgery And Transplantation
Funder
National Health and Medical Research Council
Funding Amount
$624,960.00
Summary
About one third of the population have a fatty liver, and this greatly increases risks of liver failure after liver surgery or when fatty donor livers are used for transplantation (such organs are currently disposed of). The disease process is called ischemia-reperfusion injury (IRI). The investigators have recently shown that both fibrates and statins provide partial protection against IRI in fatty livers. This research is directed at establish the protective mechanisms, and whether combination ....About one third of the population have a fatty liver, and this greatly increases risks of liver failure after liver surgery or when fatty donor livers are used for transplantation (such organs are currently disposed of). The disease process is called ischemia-reperfusion injury (IRI). The investigators have recently shown that both fibrates and statins provide partial protection against IRI in fatty livers. This research is directed at establish the protective mechanisms, and whether combination drugs are more effective.Read moreRead less
Novel Therapies Targeting The Alternate Renin Angiotensin System In Chronic Liver Disease
Funder
National Health and Medical Research Council
Funding Amount
$1,284,565.00
Summary
Scarring of the liver due to chronic liver diseases (cirrhosis) is now a major cause of illness and death in Australia. This project will study whether drugs and gene therapy approaches targeting a hormone system called the renin angiotensin system can be used to prevent the development of cirrhosis and its complications.