Targetting Monocytes With Microparticles To Prevent Kidney Allograft Rejection
Funder
National Health and Medical Research Council
Funding Amount
$967,005.00
Summary
Whilst transplantation is lifesaving for many Australians with organ failure, it is a treatment rather than cure as recipients are dependent upon lifelong immunosuppression to prevent transplant rejection. Risks of death due to infection and cancer therefore remain high. We will test a new strategy in mice which modifies recipients of monocytes at the time of transplantation, to enable them to accept and tolerate the organ without ongoing need for expensive and dangerous immunosuppressive drugs.
Heart attacks remain a major cause of morbidity and mortality. I am an interventional cardiologist who heads an expanding basic and translational science laboratory (Cardiac Oxidative Signalling) at the Kolling Institute and who plays a leading role in clinical cardiovascular research at Royal North Shore Hospital. My vision is to translate fundamental discoveries in our Laboratory to new therapies and methods of risk stratification to improve immediate and long term outcomes of patients sufferi ....Heart attacks remain a major cause of morbidity and mortality. I am an interventional cardiologist who heads an expanding basic and translational science laboratory (Cardiac Oxidative Signalling) at the Kolling Institute and who plays a leading role in clinical cardiovascular research at Royal North Shore Hospital. My vision is to translate fundamental discoveries in our Laboratory to new therapies and methods of risk stratification to improve immediate and long term outcomes of patients suffering heart attack.Read moreRead less
Dysferlinopathy: A Genetic Disease Sheds Light On Membrane Repair For Muscle And Cardiac Injury
Funder
National Health and Medical Research Council
Funding Amount
$782,806.00
Summary
Muscles are damaged all of the time, as we stretch and contract them, but we don't fully understand how they repair themselves. We are studying the molecular steps taken by a muscle cell to repair membrane damage. Our research will provide valuable insights into how to treat muscular dystrophy and other conditions characterised by membrane damage to cells, such as heart attack and stroke.
Dysferlin Coordinates Membrane Repair For Skeletal And Cardiac Injury
Funder
National Health and Medical Research Council
Funding Amount
$459,270.00
Summary
Muscles are damaged all of the time, as we stretch and contract them, but we don't fully understand how they repair themselves. We are studying the molecular steps taken by a muscle cell to repair membrane damage. Our research will provide valuable insights into how to treat muscular dystrophy and other conditions characterised by membrane damage to cells, such as heart attack and stroke.
Regulation Of The Cardiac Sodium/proton Exchanger During Ischaemia, Reperfusion And Preconditioning
Funder
National Health and Medical Research Council
Funding Amount
$101,000.00
Summary
Heart attacks are currently treated with drugs to dissolve the clot in the coronary artery or by catheterisation with the aim of restoring blood flow to the ischaemic heart muscle. If restoration of blood flow occurs soon after the heart attack, the ischaemic region can recover completely. However if treatment is delayed, the ischaemic region may not recover. This project concerns the mechanisms that are involved in the myocardial damage which occurs after moderate periods of ischaemia. A transp ....Heart attacks are currently treated with drugs to dissolve the clot in the coronary artery or by catheterisation with the aim of restoring blood flow to the ischaemic heart muscle. If restoration of blood flow occurs soon after the heart attack, the ischaemic region can recover completely. However if treatment is delayed, the ischaemic region may not recover. This project concerns the mechanisms that are involved in the myocardial damage which occurs after moderate periods of ischaemia. A transport protein, the sodium-proton exchanger, is involved in recovery and if its action is blocked with an inhibitory drug, recovery of the ischaemic myocardium is improved. However clinical trials of the drug in humans have given variable results. We are investigating the regulation of this exchanger and believe that such information is essential to the efficient use of the inhibitory drugs in humans and may identify other pathways to improving recovery after ischaemia.Read moreRead less
Contribution Of Disturbed Blood Flow And Cerebral Metabolism To White Matter Damage In The Perinatal Brain
Funder
National Health and Medical Research Council
Funding Amount
$369,375.00
Summary
It has been known for some time that the white matter regions of the developing brain are particularly vulnerable to damage. These regions are deep in the brain near the ventricles, and are rich in myelin sheaths wrapped around the nerve fibres running from cell-rich areas in the outer layers of the brain to other regions, and down into the spinal cord. Damage to white matter usually leads to behavioural, learning and motor problems in the newborn infant - in its severest form, seen as cerebral ....It has been known for some time that the white matter regions of the developing brain are particularly vulnerable to damage. These regions are deep in the brain near the ventricles, and are rich in myelin sheaths wrapped around the nerve fibres running from cell-rich areas in the outer layers of the brain to other regions, and down into the spinal cord. Damage to white matter usually leads to behavioural, learning and motor problems in the newborn infant - in its severest form, seen as cerebral palsy. Such outcomes are often associated with the presence of asphyxia and infection during pregnancy, leading to the belief that the damage first arises while the baby is still in utero. In this application we suggest that asphyxia and-or infection during pregnancy cause prolonged disturbances in the regulation of blood flow and integrity of the blood-brain barrier in the developing brain, together with changes in metabolism that result in accumulation of prostaglandins and the toxic hydroxyl radical, leading irreversibly to cell death. If this series of events proves to be true, we have suggested and will test several protocols for protecting the fetal brain, which should be readily translatable to clinical practice.Read moreRead less
DEVELOPMENT OF FOLDING IN THE FETAL CEREBRAL CORTEX – IDENTIFYING FUNDAMENTAL MECHANISMS AND THEIR SUSCEPTIBILITY TO DISRUPTION IN NORMAL AND ABNORMAL PREGNANCY
Funder
National Health and Medical Research Council
Funding Amount
$607,742.00
Summary
During pregnancy, the surface of the fetal brain gradually develops the ridges, valleys, and folds that are the characteristic feature of our highly developed brain. However, this process can be disturbed if birth occurs prematurely, the unborn baby suffers oxygen starvation in the uterus, or the mother consumes alcohol. In this project we are determining how cell migration results in the development of brain surface folding, and how hypoxia and maternal alcohol consumption affect these importan ....During pregnancy, the surface of the fetal brain gradually develops the ridges, valleys, and folds that are the characteristic feature of our highly developed brain. However, this process can be disturbed if birth occurs prematurely, the unborn baby suffers oxygen starvation in the uterus, or the mother consumes alcohol. In this project we are determining how cell migration results in the development of brain surface folding, and how hypoxia and maternal alcohol consumption affect these important processes.Read moreRead less
Targeting Innate Immunity To Prevent Chronic Dysfunction Of The Transplanted Kidney
Funder
National Health and Medical Research Council
Funding Amount
$497,057.00
Summary
Kidney transplantation is the optimal treatment for patients suffering from end-stage kidney disease. Chronic transplant dysfunction is the major barrier to long-term health after transplantation, and is the subject of this application. Our studies suggest a signaling system activates immunity and leads to chronic transplant dysfunction. We aim to block this signaling system in mouse models to identify clinically applicable treatments to prevent kidney transplant failure.
Role Of Microparticles In Cardiac Ischemia Reperfusion Injury
Funder
National Health and Medical Research Council
Funding Amount
$55,575.00
Summary
Interventional cardiology has reduced the mortality rate associated with heart attack, unfortunately the prevalence of heart failure has subsequently increased, caused in part by reperfusion injury of previously occluded vessels. We aim to identify novel insights into the pathogenesis of IR injury in the heart, as well as the development of new approaches to prevent cardiac damage during cardiac surgery, transplantation, post-angioplasty and coronary artery stenting.
Mechanisms Contributing To Long-term Neuronal Loss After Hypoxia-ischemia In The Premature Neonate Brain.
Funder
National Health and Medical Research Council
Funding Amount
$432,535.00
Summary
A lack of oxygen (hypoxia) and blood flow to the brain (ischemia) around the time of birth can cause brain injury that perists into adulthood. The burdens on financial, educational and healthcare resources are enormous. We will improve our understanding of what parts of the brain are injured and the mechanisms contributing to on-going brain injury after hypoxia-ischemia.This is important to devise treatments and to provide a healthy start to life for neonates.