Morbidity and mortality secondary to liver disease is greatly increased in people co-infected with HIV and HBV compared to those infected with HBV alone. Mortality remains elevated even after treating both viruses. This project will investigate the mechanism of how HIV accelerates liver disease in patients co-infected with HBV. We hypothesize that this occurs by combined effects of HIV and HBV on inflammation in the liver. These studies could potentially lead to new treatments for liver disease.
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.
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.
Improved Health Outcomes For People Living With HIV
Funder
National Health and Medical Research Council
Funding Amount
$560,284.00
Summary
Despite the success of antiviral therapy for HIV infection, HIV cannot be cured and treatment is life long. In addition, there are complications in patients on long term antiviral therapy due to impaired immune recovery. This grant will identify strategies to eliminate HIV from latently infected cells that persist in patients on antiviral therapy as well as identify novel ways to improve the immune response to antiviral treatment for patients with HIV infection as well as patients co-infected wi ....Despite the success of antiviral therapy for HIV infection, HIV cannot be cured and treatment is life long. In addition, there are complications in patients on long term antiviral therapy due to impaired immune recovery. This grant will identify strategies to eliminate HIV from latently infected cells that persist in patients on antiviral therapy as well as identify novel ways to improve the immune response to antiviral treatment for patients with HIV infection as well as patients co-infected with hepatitis B virus (HBV)Read moreRead less
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