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
NAFLD, NASH And Hepatocellular Carcinoma: Mechanisms & Potential Treatments
Funder
National Health and Medical Research Council
Funding Amount
$692,992.00
Summary
Liver cancer is one of the most common and fatal cancers world-wide. In developed countries, the past three decades has seen its incidence treble becoming the fastest rising cause of cancer deaths. In some patients liver cancer seems to be caused by obesity. The reason why some obese patients get liver cancer and others do not is unknown. In addition, there are few treatment options. In these studies we will research what causes liver cancer in obesity and test two new potential therapies.
How Does Dietary Cholesterol Induce Non-alcoholic Steatohepatitis?
Funder
National Health and Medical Research Council
Funding Amount
$802,600.00
Summary
Non-alcoholic fatty liver disease is the most common liver disease that can progress to non-alcoholic steatohepatitis (NASH), cirrhosis and liver cancer. Dietary cholesterol is a major risk factor for NASH. We can demonstrate that cholesterol changes the gut bacteria. These bacteria generate toxic chemicals (bile acids) that signal to the liver and induce NASH. In this project, we use novel ways to clarify the mechanisms of liver inflammation and test novel therapeutic approaches to reverse it.
Characterization Of ARL6IP5 In Hepatitis C-related Liver Cancer
Funder
National Health and Medical Research Council
Funding Amount
$505,283.00
Summary
The incidence and mortality from liver cancer is increasing rapidly in Australia, and hepatitis C virus infection is the most common cause. How hepatitis C leads to liver cancer is largely unknown. We identified a novel gene termed ARL6IP5 that appears to be specifically increased in liver tissue by chronic hepatitis C infection. In this project we will characterize the involvement and role of this gene in liver cancer development. Knowledge gained from this study will help us understand how hep ....The incidence and mortality from liver cancer is increasing rapidly in Australia, and hepatitis C virus infection is the most common cause. How hepatitis C leads to liver cancer is largely unknown. We identified a novel gene termed ARL6IP5 that appears to be specifically increased in liver tissue by chronic hepatitis C infection. In this project we will characterize the involvement and role of this gene in liver cancer development. Knowledge gained from this study will help us understand how hepatitis C leads to cancer.Read moreRead less
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.
A Pilot Study To Evaluate The Safety Of Intravenously Administered Human Amnion Epithelial Cells In Patients With Compensated Cirrhosis
Funder
National Health and Medical Research Council
Funding Amount
$394,692.00
Summary
We propose a first-in-man clinical trial of human amnion epithelial cells (hAEC), a stem cell from the placenta, to assess safety in patients with stable liver cirrhosis. Worldwide, cirrhosis is the 6th most common cause of death. Liver transplantation remains the only chance for survival for some people with cirrhosis. In animal models, hAEC can substantially reduce liver scar tissue. Our goal is to develop hAEC as a therapy to reduce the need for liver transplantation.
Novel Therapies Targeting The Alternate Renin Angiotensin System In Chronic Liver Disease
Funder
National Health and Medical Research Council
Funding Amount
$1,284,565.00
Summary
Scarring of the liver due to chronic liver diseases (cirrhosis) is now a major cause of illness and death in Australia. This project will study whether drugs and gene therapy approaches targeting a hormone system called the renin angiotensin system can be used to prevent the development of cirrhosis and its complications.
Studies Of The Role Of The Hepatocyte In The Response To HCV Infection
Funder
National Health and Medical Research Council
Funding Amount
$513,294.00
Summary
Infection with hepatitis C (HCV) affects 120 million individuals worldwide, and over 200,000 in Australia. HCV-related liver disease is the most common indication for liver transplantation in Australia and rates of HCV-related liver failure and hepatocellular cancer are predicted to increase as the HCV population ages. A new test for the IL28B gene, has shown to be the strongest predictor of cure after treatment. The mechanism of this association is unknown and is the subject of this grant.
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
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.