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
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.Read moreRead less
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.
A Novel Treatment For Ischemic Stroke: Preclinical Assessment In The Nonhuman Primate
Funder
National Health and Medical Research Council
Funding Amount
$762,246.00
Summary
A major source of repair inhibition after brain injury is debris from dying cells, which contains proteins that hinder repair. This project will examine the expression of these proteins in a clinically-relevant model of ischemic stroke and determine if blocking the effect of these proteins neutralises their repair-inhibiting properties. If successful, there is likelihood that this drug, and method of delivery, could be translated into the human for treatment following an ischemic stroke.
Next Generation Cybernetics: Long Term Carbon Fibre Dual Stimulation / Recording Electrode Arrays For Closed Loop Neural Implants
Funder
National Health and Medical Research Council
Funding Amount
$679,670.00
Summary
Electrodes implanted in the brain have enormous potential for treating a range of conditions from epilepsy to control of prosthetics for patients with limb loss. Currently, the electrodes used in such system fail rapidly because they are rejected by the body. We aim to use diamond with ultra-fine carbon fibre electrodes to make arrays that are invisible to the human immune system. Such arrays will function for the lifetime of the patient without needing replacement.
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.
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.Read moreRead less
Reprogramming Macrophage Function In The Elderly To Rescue Impaired Inflammatory Responses To Muscle Injury
Funder
National Health and Medical Research Council
Funding Amount
$410,983.00
Summary
Muscle injury in the elderly often takes longer to heal than in younger people, however the cells responsible for this delayed healing are not well understood. Key inflammatory cells required for muscle repair in young hosts are macrophages. However, during aging we have shown that macrophage function is altered, but the mechanism is unknown. This project aims to determine the mechanisms behind age-related changes to macrophages and whether they can be targeted to improve elderly muscle repair.
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.
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.