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Country : Australia
Research Topic : Liver cirrhosis
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  • Funded Activity

    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
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    Funded Activity

    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.
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    Funded Activity

    Novel Vasoactive Pathways In Liver Disease; Experimental And Clinical Studies

    Funder
    National Health and Medical Research Council
    Funding Amount
    $535,333.00
    Summary
    Cirrhosis of the liver due to chronic hepatitis and other common liver diseases is now a major cause of illness and death in Australia. This project will examine how a hormone system called the renin angiotensin system contributes to the development of liver damage in these diseases. We will study whether drugs targeting this system can be used to reduce liver scarring and prevent the development of cirrhosis and its complications.
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    Funded Activity

    Hepatic Fibrogenesis In Paediatric Cholestatic Liver Disease.

    Funder
    National Health and Medical Research Council
    Funding Amount
    $254,250.00
    Summary
    Liver disease in children causes a significant impact on lifespan and quality of life. The commonest causes of liver disease in children are cholestatic, or diseases related to obstruction of bile flow out of the liver. In ways we are only beginning to understand, obstruction of bile flow stimulates liver scar formation which, if untreated, leads to replacement of normal liver tissue and ultimately to failure of the liver. In infants, the most common and serious cholestatic liver disease is bili .... Liver disease in children causes a significant impact on lifespan and quality of life. The commonest causes of liver disease in children are cholestatic, or diseases related to obstruction of bile flow out of the liver. In ways we are only beginning to understand, obstruction of bile flow stimulates liver scar formation which, if untreated, leads to replacement of normal liver tissue and ultimately to failure of the liver. In infants, the most common and serious cholestatic liver disease is biliary atresia. It develops at, or shortly after birth with progressive destruction of the bile ducts, responsible for transporting bile out of the liver. Without early diagnosis and surgery these infants develop progressive liver scarring leading to liver failure and death or liver transplantation within 1-2 years. It is the commonest reason for liver transplantation in children (55-60%) in the Western world. Even with successful surgery, most, if not all patients will come to liver transplantation over the subsequent 25 years because of ongoing, but slower, scar formation. In older children, diseases like cystic fibrosis cause bile duct blockages leading to progressive liver scarring that is slower and unpredictable, contributing to ill health in up to 20% of patients and death from end stage liver disease or liver transplantation in 5%. Using liver tissue from children with these two disorders we have been able to identify the key cells that control the liver scar process, the Hepatic Stellate Cell. We now need to investigate the role of bile constituents on the scar-forming process in these two diseases. We will utilise a well characterised animal model to investigate the influence of bile constituents on cells isolated from this model and apply these findings back to patient samples to determine their role in paediatric cholestatic liver disease. This will help us to better understand the disease process and importantly, develop more effective and earlier treatment.
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    Funded Activity

    Tissue Ferritin Acts As A Proinflammatory Mediator Of Hepatic Fibrosis In Chronic Liver Disease Via Multiple Receptors In Hepatic Stellate Cells Responsible For Both Binding And Signalling.

    Funder
    National Health and Medical Research Council
    Funding Amount
    $777,887.00
    Summary
    Our research has identified a role for tissue-derived ferritin as a proinflammatory cytokine in hepatic stellate cell biology, the cells responsible for liver scarring (fibrosis) in Haemochromatosis. This proposal will identify the receptor responsible for eliciting ferritin's proinflammatory action and assess its role in fibrosis. This study will have implications in chronic liver diseases of varying aetiologies where elevated serum ferrritin is associated with inflammation.
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    Funded Activity

    Mechanisms Of Hepatic Fibrogenesis In Chronic Liver Disease

    Funder
    National Health and Medical Research Council
    Funding Amount
    $697,209.00
    Summary
    Despite advances made in understanding the mechanisms of liver injury, chronic liver disease continues to be one of the most rapidly growing causes of death in subjects aged <65 years. This is the result of uncontrolled wound healing and regeneration leading ultimately to cirrhosis and liver cancer. This research will identify and characterise pathways that control the wound healing response to liver injury, involving the processes of inflammation, scarring and restitution of normal liver mas .... Despite advances made in understanding the mechanisms of liver injury, chronic liver disease continues to be one of the most rapidly growing causes of death in subjects aged <65 years. This is the result of uncontrolled wound healing and regeneration leading ultimately to cirrhosis and liver cancer. This research will identify and characterise pathways that control the wound healing response to liver injury, involving the processes of inflammation, scarring and restitution of normal liver mass.
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    Funded Activity

    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.
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    Funded Activity

    Identification Of The Mechanisms Of Hepatic Fibrogenesis Aid In The Detection And Prediction Of Clinical Outcomes In Paediatric Cholestatic Liver Disease.

    Funder
    National Health and Medical Research Council
    Funding Amount
    $624,429.00
    Summary
    Biliary Atresia (BA) and Cystic Fibrosis Liver Disease (CFLD) are important causes of childhood cirrhosis. Diagnosis is difficult, treatments problematic, and outcomes suboptimal. In BA, bile duct obstruction in infants rapidly progresses to liver failure. It is the most common indication for liver transplantation in children. CFLD causes significant morbidity/mortality in about 20% of CF children. This proposal investigates the mechanisms of liver fibrosis (scarring) and the role of fibrosis in .... Biliary Atresia (BA) and Cystic Fibrosis Liver Disease (CFLD) are important causes of childhood cirrhosis. Diagnosis is difficult, treatments problematic, and outcomes suboptimal. In BA, bile duct obstruction in infants rapidly progresses to liver failure. It is the most common indication for liver transplantation in children. CFLD causes significant morbidity/mortality in about 20% of CF children. This proposal investigates the mechanisms of liver fibrosis (scarring) and the role of fibrosis in both diagnosis and predicting clinical outcome.
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    Funded Activity

    HLA-G/H2-Bl Is Critical For Regulating Inflammation In The Liver

    Funder
    National Health and Medical Research Council
    Funding Amount
    $494,050.00
    Summary
    The key factor to induction of liver fibrosis, progression to cirrhosis, and hepatocellular carcinoma is inflammation. Liver transplant and liver regeneration following liver resection are also dramatically impaired by elevation of inflammation. We have identified a potent anti-inflammatory protein, HLA-G, that is critical for regulating post-surgical inflammation in the liver. We will determine if HLA-G can reverse and/or block liver fibrosis and modify HLA-G for improved clinical potential.
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    Funded Activity

    Role Of Chemoattractants In Hepatic Stellate Cell Recruitment And Fibrogenesis In Paediatric Cholestatic Liver Disease.

    Funder
    National Health and Medical Research Council
    Funding Amount
    $589,175.00
    Summary
    This project investigates how decreased bile flow in children's liver diseases such as cystic fibrosis and biliary atresia, leads to the release of molecules from the liver which cause recruitment of scar-forming cells. This results in cirrhosis (liver scar) and the necessity for liver transplantation. This project will investigate whether some children are more susceptible to liver scarring due to mutations in genes which cause increased release of these recruitment molecules from the liver.
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