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.
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.
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.
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.
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
The Role Of The Hepatocyte And EMMPRIN In Liver Injury
Funder
National Health and Medical Research Council
Funding Amount
$607,487.00
Summary
This research plan investigates the role of the hepatocyte, the principal functional cell within the liver in the development of liver disease. Liver injury can result in end-stage scaring known as cirrhosis as well as leading to liver cancer. Our research aims to identify strategies for reversing the fibrotic process and result damage to the liver
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
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.