Regulation Of Angiotensin-Converting Enzyme -2 Expression In Liver Injury
Funder
National Health and Medical Research Council
Funding Amount
$302,764.00
Summary
Very recent studies suggest Angiotensin-Converting Enzyme-2 (ACE2) a newly discovered enzyme, normally undetectable in the liver is markedly increased in liver disease in both man and rats. We have recently identified human liver cell lines that endogenously express ACE2 giving us a unique opportunity to investigate the function of this enzyme. The aim of the present project is to provide further insights into the role of ACE2 in liver disease by determining the regulation, location and transpor ....Very recent studies suggest Angiotensin-Converting Enzyme-2 (ACE2) a newly discovered enzyme, normally undetectable in the liver is markedly increased in liver disease in both man and rats. We have recently identified human liver cell lines that endogenously express ACE2 giving us a unique opportunity to investigate the function of this enzyme. The aim of the present project is to provide further insights into the role of ACE2 in liver disease by determining the regulation, location and transport of ACE2 in cultured liver cells as well as in rat models of liver injury.Read moreRead less
HFE-associated Steatohepatitis: Mechanisms And Therapies
Funder
National Health and Medical Research Council
Funding Amount
$650,813.00
Summary
Iron and fat alter normal iron metabolism and cause more severe disease in combination. In this study we will study the relationship between liver disease caused by increased body iron and the consumption of excess fat and the causal mechanisms. We will then examine new therapies for the treatment of iron-associated fatty liver disease.
Targeting The Pathophysiology And Therapy Of Liver Fibrosis
Funder
National Health and Medical Research Council
Funding Amount
$484,006.00
Summary
Hepatic fibrosis, or scarring of the liver, is a serious condition which can lead to liver cancer or death. Treatment of liver scarring is currently not effective once the scarring is well developed. This project aims to examine agents which may act to halt liver scarring once it has already developed. Outcomes from this project may help provide potential treatments to reduce the need for liver transplantation or to reduce patient deaths.
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
The Role Of The Adiponectin Receptors In Liver Fibrosis
Funder
National Health and Medical Research Council
Funding Amount
$393,159.00
Summary
Advanced liver scarring (fibrosis) contributes to the death of 1500 Australians annually. Two-thirds of our community is overweight or obese, and this worsens liver disease. A protein secreted by fat, adiponectin, may be important as it acts on liver cells to promote fibrosis. To understand adiponectins role, we will use mice null for adiponectin receptor genes and study its action on liver cells. This study will improve our understanding of liver scarring biology and patient treatments.
Adiponectin And Cholesterol: A Driving Force In NASH Immunopathogenesis
Funder
National Health and Medical Research Council
Funding Amount
$436,017.00
Summary
This project examined the role of dietary cholesterol in the pathogenesis of fatty liver disease in a rodent model. We have been able to demonstrate that diets high in cholesterol lead to the development of inflammatory foci in the liver, elevations in the amount of hepatic ceramides (a lipid byproduct) and then leads to the activation of inflammatory molecular pathwways that lead to liver fibrosis. The latter results in end stage liver disease, and in some to the development of liver cancer.
THE ROLE OF THE HEPATOCYTE IN EXTRACELLULAR MATRIX INTERACTIONS IN LIVER FIBROGENESIS
Funder
National Health and Medical Research Council
Funding Amount
$540,438.00
Summary
This study focuses on the main cell within the liver, the hepatocyte, and its role in the development of liver fibrosis. Liver fibrosis arising from liver injury has a common progression characterised by loss of liver structure and the development of dense fibrous bands of tissue in the condition known as cirrhosis. The importance of the outlined research plan is that for the first time the hepatocyte has been identified as having a significant role in the development of liver fibrosis.