Liver damage after liver surgery or shock is called ischemia-reperfusion injury (IRI). Recovery after surgical removal of liver tissue is due to liver regeneration. IRI and liver regeneration are controlled by specialised proteins called cytokines, one of which, TRAIL, is essential for both IRI and liver regeneration. This research is to find out how TRAIL exerts such seemingly opposite effects. The aim is to learn how to protect the liver against damage, and to stimulate its recovery.
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
The Role Of TNF And Its Receptor Family In Liver Progenitor Cell Proliferation And Differentiation
Funder
National Health and Medical Research Council
Funding Amount
$250,500.00
Summary
Maintaining liver function is essential for health, and compromising this ultimately results in death. The liver is unusual, as it can regenerate to replace lost or damaged tissue. Recently it has been established that there are two pathways to liver regeneration. One involves hepatocytes, and this is normally associated with acute liver damage. The other, involves liver progenitor cells; and this is usually observed when there is chronic and severe liver damage, particularly when the proliferat ....Maintaining liver function is essential for health, and compromising this ultimately results in death. The liver is unusual, as it can regenerate to replace lost or damaged tissue. Recently it has been established that there are two pathways to liver regeneration. One involves hepatocytes, and this is normally associated with acute liver damage. The other, involves liver progenitor cells; and this is usually observed when there is chronic and severe liver damage, particularly when the proliferation of hepatocytes is impaired. This study seeks to understand the underlying mechanisms which recruit liver progenitor cells for regeneration. This knowledge can lead to strategies to augment the oval cell contribution to liver regeneration in cases of chronic liver damage, to enhance survival of the patient. It can be applied to strategies to grow and maintain liver stem cells in culture for the purpose of cell and gene therapy to correct liver dysfunction. It is also necessary to identify factors which affect oval cells and understand their mechanism of action because of their link to liver cancer. Oval cells have a Jekyll and Hyde characteristic, and it is important to know what leads them towards liver differentiation and regeneration, and what makes them produce liver cancers.Read moreRead less
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.
Mechanisms Underlying Growth, Lineage Commitment And Differentiation Of Liver Progenitor Cells
Funder
National Health and Medical Research Council
Funding Amount
$535,333.00
Summary
Liver disease is a serious health problem. Viral hepatitis, obesity and alcohol can result in end-stage liver disease. Organ transplant is the only treatment available. A widening gap between organ donations and recipients mandates alternative treatments are developed. Cell transplantation and artificial liver devices are alternatives which can use liver progenitor cells. We will investigate how factors grow and convert them into liver cells for treating liver disease patients.
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.
The Epidemiology And Burden Of Liver Disease In Australia With An Emphasis On Non-alcoholic Fatty Liver Disease.
Funder
National Health and Medical Research Council
Funding Amount
$151,143.00
Summary
Non alcoholic fatty liver disease is now the commonest cause of abnormal liver function in Australia due to its close association with the obesity epidemic. It is likely to become the leading cause of liver failure and liver cancer over the next few decades. Despite this, the prevalence in Australian populations is unknown. The aim of this project is to assess how common this disorder is, the burden it places on the healthcare system and the effectiveness of treatment for liver cancer caused by ....Non alcoholic fatty liver disease is now the commonest cause of abnormal liver function in Australia due to its close association with the obesity epidemic. It is likely to become the leading cause of liver failure and liver cancer over the next few decades. Despite this, the prevalence in Australian populations is unknown. The aim of this project is to assess how common this disorder is, the burden it places on the healthcare system and the effectiveness of treatment for liver cancer caused by advanced non alcoholic fatty liver disease.Read moreRead less
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.