Microparticles In NASH: Origins, Pathogenic Roles, And Biomarker Of Disease Activity
Funder
National Health and Medical Research Council
Funding Amount
$540,633.00
Summary
30% of Australians have non-alcoholic fatty liver disease (NAFLD). Cirrhosis is the third cause of death; only 10-25% of NAFLD livers show steatohepatitis (NASH), which leads to cirrhosis. We have found that microparticles (MPs), small fragments of cell membranes, circulate in NASH but not in ordinary fatty liver. We will now explore ways in which MPs incite inflammation and liver fibrosis in NASH, and design new tests based on MPs to improve clinical assessment of patients with NAFLD/NASH.
Development Of Functional Liver Tissue Engineered From Murine Hepatocyte Or Liver Progenitor Cell Spheroids To Correct Liver Disease
Funder
National Health and Medical Research Council
Funding Amount
$459,482.00
Summary
Many patients suffering from severe liver disease require a liver transplant, but due to a shortage of liver donors, many die prior to liver transplantation. This study investigates novel methods of growing liver tissue from mature liver cells called hepatocytes, or, liver stem cells implanted in a plastic chamber in mice with acute and chronic liver disease. It is anticipated that new liver tissue will grow in the chamber, the mice will be cured, and that this technique can be translated to hum ....Many patients suffering from severe liver disease require a liver transplant, but due to a shortage of liver donors, many die prior to liver transplantation. This study investigates novel methods of growing liver tissue from mature liver cells called hepatocytes, or, liver stem cells implanted in a plastic chamber in mice with acute and chronic liver disease. It is anticipated that new liver tissue will grow in the chamber, the mice will be cured, and that this technique can be translated to humans with liver disease.Read moreRead less
Cellular Therapy For Genetic Liver Disease Exploiting Induced Pluripotent Stem Cells And Liver Progenitor Cells
Funder
National Health and Medical Research Council
Funding Amount
$797,185.00
Summary
It has recently become possible to genetically reprogram mature cell types in the body to become stem cells and then redirect them to become any other cell type desired. This technology has immense, but as yet unrealised, diagnostic and therapeutic potential. In this project we seek to develop cellular therapies for metabolic liver disease. Specifically, we plan to generate liver cells from skin cells and to test the therapeutic effectiveness of these cells by curing liver disease in mice.
Physiologically-based Pharmacokinetics And Pharmacodynamics Of Therapeutic Stem Cells For Liver Disease
Funder
National Health and Medical Research Council
Funding Amount
$848,710.00
Summary
This project focuses on the challenging area of effective and optimal dosing cell-based therapy for liver diseases. We will investigate the fate and therapeutic effects of natural, modified and artificial therapeutic cells in the body and in liver regions using a physiologically-based kinetic model. Our key goal is advance cell therapy by providing a better understanding and dosing guidelines.
A Unique Network Of Phagocytic Cells At The Interface Between The Liver And Peritoneal Cavity
Funder
National Health and Medical Research Council
Funding Amount
$787,521.00
Summary
This project aims to characterise the nature and ontogeny of a novel population of cells with phagocytic capacity that forms a network underlying the capsule of mouse and human liver reminiscent of that formed by Langherans cells in the epidermis of the skin. In this project we will characterise this newly described liver capsular macrophage subset, define their ontogeny and assess their specific functions.
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.
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