Cellular Cross-talk Between Liver Progenitor Cells And Hepatic Stellate Cells Is Required For Hepatic Fibrogenesis
Funder
National Health and Medical Research Council
Funding Amount
$618,517.00
Summary
Deloitte Access Economics data proposes the total economic burden of liver disease in Australia in 2012 was >$50 billion. This study will identify how the liver heals itself by inducing liver cell populations which interact to regenerate damaged liver tissue in chronic liver disease. This knowledge may lead to the development of novel therapeutic interventions for the treatment of liver scarring and liver cancer, and to assist in normal liver regeneration following chronic liver disease.
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 Hepatic Stellate Cell And Liver Progenitor Cell Interactions In The Regulation Of Wound Healing And Liver Regeneration
Funder
National Health and Medical Research Council
Funding Amount
$620,716.00
Summary
The liver has a remarkable capacity for regeneration following acute and chronic liver injury, however, the mechanisms which facilitate this wound healing are not understood. This project will examine the interactions between different liver cell populations, including hepatic stellate cells (liver fibroblasts) and liver progenitor cells (stem cells of the liver) and will determine which factors regulate inflammation, liver scarring and restitution of liver mass following chronic liver injury.
Alcoholic Chronic Pancreatitis: Induction, Progression And Reversal
Funder
National Health and Medical Research Council
Funding Amount
$632,211.00
Summary
Pancreatitis (inflammation of the pancreas) is a serious complication of alcohol abuse. Patients suffer from severe and often intractable abdominal pain, maldigestion and diabetes, We have recently shown that gut toxins (endotoxins) may act as a trigger factor for pancreatitis in alcoholics. The proposed project aims to characterise the effects of gut toxins on the pancreas during alcohol abuse so as to identify pathways that may be therapeutically targeted to prevent or retard the disease.
Alcoholic Pancreatitis : Role Of Alcohol, Endotoxin And Stellate Cells
Funder
National Health and Medical Research Council
Funding Amount
$501,653.00
Summary
The pancreas is the major digestive organ of the body. It contains many proteins (enzymes) which break down food. One of the more serious complications of alcohol (ethanol) abuse is pancreatitis, a condition that has both acute and chronic manifestations. Patients with acute pancreatitis suffer from acute abdominal pain; in severe cases the condition can be fatal. Repeated attacks of acute pancreatitis can lead to chronic pancreatitis, a condition in which, normal pancreatic tissue is lost and i ....The pancreas is the major digestive organ of the body. It contains many proteins (enzymes) which break down food. One of the more serious complications of alcohol (ethanol) abuse is pancreatitis, a condition that has both acute and chronic manifestations. Patients with acute pancreatitis suffer from acute abdominal pain; in severe cases the condition can be fatal. Repeated attacks of acute pancreatitis can lead to chronic pancreatitis, a condition in which, normal pancreatic tissue is lost and is replaced by scarring. This disease causes chronic pain, inability to digest food with consequent malnutrition and destruction of the insulin producing cells of the gland leading to diabetes. The mechanisms by which alcohol causes pancreatitis are not yet known. Although it is well established that the risk of developing pancreatitis increases with increasing intake of alcohol, suggesting that alcohol exerts toxic effects on the gland, it is also clear that not all alcoholics develop pancreatitis, indicating that an additional trigger factor-susceptibility factor is required to produce overt disease. The proposed project aims to determine the mechanisms responsible for alcohol-induced acute and chronic pancreatitis. It seeks i) to determine whether toxins from gut bacteria (endotoxins) may act as the trigger factor for acute alcoholic pancreatitis; and ii) to characterise the effects of alcohol and endotoxin on the cells responsible for pancreatic scarring, namely, pancreatic stellate cells. Our experiments will involve an animal model of alcohol feeding as well as pancreatic cells grown in dishes (cultured cells). Identification of the pathways by which alcohol causes pancreatic injury may enable the development of treatment strategies to prevent and-or retard the progress of alcoholic pancreatitisRead 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.
Metabolically Reprogramming The Stroma To Starve Pancreatic Tumours
Funder
National Health and Medical Research Council
Funding Amount
$598,848.00
Summary
Pancreatic cancer claims five Australian lives every day. Despite aggressive treatment regimes, there has been no improvement in patient survival in the last decade. Evidence suggests that targeting cancer cells alone is not enough. Pancreatic tumours are surrounded by an extensive scar tissue reaction (stroma). This intense stromal reaction inhibits drug delivery and increases tumour growth. Thus, decreasing the stroma is a potential therapeutic strategy and is the focus of this proposal.
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.Read moreRead less
Targeting Tumour-Stromal Interactions In Pancreatic Cancer
Funder
National Health and Medical Research Council
Funding Amount
$410,095.00
Summary
Pancreatic cancer claims five Australian lives every day and is one of the nations most lethal diseases. Despite aggressive treatment regimes, there has been no improvement in patient survival in the last decade. Evidence suggests that targeting cancer cells alone is not enough. The intense stromal reaction inhibits drug delivery and increases the aggressiveness of the tumours. Thus, depletion of the stroma or pancreatic stellate cells is a potential therapeutic target.