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.
Creating A Vascularized Human Liver Organoid To Treat Liver Disease
Funder
National Health and Medical Research Council
Funding Amount
$696,968.00
Summary
Due to a shortage of donor livers many patients suffering liver failure die before a liver transplant can be arranged. This project will grow human liver tissue (termed a liver organoid) using a specilaized human liver support material in which human liver cells and their specific blood vessels are assembled in the laboratory. The liver organoid will be transplanted into animals with a liver disease similar to a known human liver disease to test if the organoid can cure the liver disease.
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
A Targeted Approach To Age Related Disease: Nanomedicines And The Liver Sinusoidal Endothelium
Funder
National Health and Medical Research Council
Funding Amount
$560,241.00
Summary
Cells that line the liver blood vessels undergo predictable and distinct changes with age that increase the risk of developing diseases of older age like Diabetes and Cardiovascular Disease. We can now selectively target the changes in the liver cells with nanomedicines to prevent and treat these changes. The implications of this study are vast – a new therapy for the prevention and treatment of age-related cardiovascular disease and diabetes.
Identification Of The Molecular Genetic Basis Of The Hepatic Veno-occlusive Disease With Immunodeficiency Syndrome
Funder
National Health and Medical Research Council
Funding Amount
$224,250.00
Summary
One of the most serious complications of bone marrow transplantation is veno-occlusive disease (VOD), also termed sinusoidal obstruction syndrome (SOS). This condition occurs in 10% of transplanted patients and is characterised by abnormalities of liver function, enlargement of the liver, clotting abnormalities, fluid retention and finally failure of multiple organs and death in 30-50% of cases. The cause of VOD is unknown, and its occurrence cannot be predicted in individual patients. Eight fam ....One of the most serious complications of bone marrow transplantation is veno-occlusive disease (VOD), also termed sinusoidal obstruction syndrome (SOS). This condition occurs in 10% of transplanted patients and is characterised by abnormalities of liver function, enlargement of the liver, clotting abnormalities, fluid retention and finally failure of multiple organs and death in 30-50% of cases. The cause of VOD is unknown, and its occurrence cannot be predicted in individual patients. Eight families have been described in whom a number of individuals have succumbed to a condition which is clinically and histologically indistinguishable from VOD. Affected individuals also have a form of immunodeficiency (hence termed VODI), and the abnormalities are inherited in an autosomal recessive pattern. All eight are of Lebanese origin, suggesting that a single genetic ancestral mutation was responsible for the disorder in all families, who are distantly related. We have access to genetic material from three of these families, and are on the way to identifying the causative genetic abnormality. We hypothesise that understanding this abnormality will lead to an understanding of VOD which occurs after bone marrow transplantation. We have used 800 polymorphic genetic markers scattered throughout the genome to identify the location of the genetic abnormality, and have localised the defect to a region of chromosome 2 which contains approximately 37 known and predicted genes. We now aim to determine which of the gene(s) in the candidate region is responsible for VODI, and plan to examine DNA from individuals who have had VOD after transplantation to determine if they have a related abnormality. Finding the VODI gene will benefit these families through the availability of carrier detection and may also lead to an understanding of the veno-occlusive disease that occurs after bone marrow transplantation.Read moreRead less
Restoring Microcirculatory Perfusion In ST-elevation Myocardial Infarction: The RESTORE MI Study
Funder
National Health and Medical Research Council
Funding Amount
$3,274,537.00
Summary
Current heart attack treatments have focussed on re-opening the blocked coronary artery but despite this, many patients still suffer significant heart damage because of inadequate blood flow to the heart muscle due to damage to the small blood vessels - the microcirculation. This study seeks to identify heart attack patients with damage to the microcirculation and will conduct a randomised trial of clot busting medications to reduce microcirculation damage and to improve heart function.