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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.
When Prometheus Needs A Hand – How Human Amnion Epithelial Cells Resolve Fibrosis And Regenerate The Liver
Funder
National Health and Medical Research Council
Funding Amount
$530,653.00
Summary
Cirrhosis can progress to end stage disease for which transplantation provides the only hope for survival. Liver donors in Australia are scarce; the need for donor organs is increasing. Using stem cells to repair and regenerate damaged liver may provide an alternative to organ transplantation. We are studying placental stem cells that can decrease inflammation and increase progenitor cells to repair and regenerate liver. Our goal is to use these stem cells as treatment for human liver disease
Role Of Tissue Ferritin As A Proinflammatory Mediator Of Hepatic Stellate Cell Activation In Hepatic Iron Overload.
Funder
National Health and Medical Research Council
Funding Amount
$574,890.00
Summary
The hepatic stellate cell is responsible for liver scarring (fibrosis) in chronic liver diseases such as the iron overload condition Haemochromatosis. Our research has identified a role for tissue-derived ferritin as a proinflammatory cytokine in hepatic stellate cell biology. This proposal will examine the mechanisms associated with ferritin's proinflammatory action and assess its role in the fibrosis which occurs in Haemochromatosis.
EXAMINING THE RELATIONSHIP BETWEEN MATRIPTASE-2 AND HEMOJUVELIN, TWO ESSENTIAL REGULATORS OF IRON HOMEOSTASIS
Funder
National Health and Medical Research Council
Funding Amount
$533,541.00
Summary
The control of iron levels is important in health and well being. Too little can lead to iron deficiency and anaemia, conversly too much can lead to haemochromatosis and tissue damage. We will examine the role of two proteins, matriptase-2 and hemojuvelin that when mutated cause iron deficiency or iron overload respectively. We will study how these proteins interact and work in opposite directions to control iron levels. The results will help to develop new therapeutics for iron disorders.
SARA: Delineating Its Association With The Onset And Development Of Liver Fibrosis
Funder
National Health and Medical Research Council
Funding Amount
$865,972.00
Summary
Liver disease, a significant burden on society, affects many in the prime of their life. Scarring of the liver is a response to injury due to many factors including alcohol, viruses, obesity, and fatty-liver disease. We have identified a protein associated with liver injury. In this project we will perform a systematic analysis to understand the role of this protein in injury progression. Ultimately we intend to develop tools to prevent and treat liver injury.
Inflammatory Mediators Of Liver Injury In Chronic Hepatitis C
Funder
National Health and Medical Research Council
Funding Amount
$349,336.00
Summary
Presently, liver disease from chronic hepatitis C and obesity represents a major health problem. Overall, approximately 50% of Australians with chronic hepatitis C are obese and these patients are at significantly increased risk of rapidly progressing to liver failure. It is now recognized that fat derived factors play an important role in regulating inflammatory responses. This grant proposal aims to gain insight into how liver and fat derived inflammatory factors interact to promote increased ....Presently, liver disease from chronic hepatitis C and obesity represents a major health problem. Overall, approximately 50% of Australians with chronic hepatitis C are obese and these patients are at significantly increased risk of rapidly progressing to liver failure. It is now recognized that fat derived factors play an important role in regulating inflammatory responses. This grant proposal aims to gain insight into how liver and fat derived inflammatory factors interact to promote increased liver damage in chronic hepatitis C and obesity.Read moreRead less
Tissue Ferritin Is A Damage-associated Molecular Pattern (DAMP) In Inflammasome-induced Inflammation Associated With Hepatic Stellate Cell Activation And Fibrogenesis In Chronic Liver Disease.
Funder
National Health and Medical Research Council
Funding Amount
$783,612.00
Summary
We have generated considerable evidence for a role for tissue ferritin as a mediator of inflammation associated with liver fibrosis (scarring) These highly novel and innovative studies will assist in identifying pathways involved in the proinflammatory phenotype of hepatic stellate cells (scar-forming cells in the liver) in chronic liver disease and thus will greatly aid in understanding how liver scarring occurs in chronic liver disease.
Targeting The Sympathetic Nervous System To Reduce The Burden Of Fatty Liver Disease
Funder
National Health and Medical Research Council
Funding Amount
$728,152.00
Summary
The metabolic syndrome is characterised by abdominal obesity, high blood pressure and an increased risk of diabetes development. It is clear from our own observations that the sympathetic nervous system (SNS) is important in the generation of obesity-related illness and, through its stimulation of the liver, plays an important role in the development of obesity-related liver disease. We will target the SNS in order to reduce the burden of obesity-related liver disease.
Assessment Of Oxidant Stress And Mitochondrial Dysfunction In Young Adults With Iron Loading Diseases
Funder
National Health and Medical Research Council
Funding Amount
$601,979.00
Summary
Disorders of iron metabolism are particularly prevalent in Australia and the consequences of excess iron can be severe. Liver disease is frequently associated with iron loading. The commonest form of iron loading can be treated readily, but it is unclear when the first signs of tissue damage occur and thus at what stage treatment should commence. This project will examine in detail the relationship between body iron levels and signs of tissue damage in young subjects with iron loading disease.
Hepatitis C affects a quarter of a million Australians, causing insidious but progressive liver disease which culminates in liver failure or cancer. There is no vaccine and prevention programs have limited effectiveness, but new antiviral therapies now offer high rates of cure. This Program will evaluate strategies to improve the health of those affected and prevent new infections by better understanding of the virus and the body’s immune response, including scarring and liver cancer formation.