Suppression Of NADPH Oxidase-derived Oxidative Stress By Anti-sense Probes And HDL In Human Vascular Endothelium
Funder
National Health and Medical Research Council
Funding Amount
$455,250.00
Summary
In Australia, coronary heart disease (CHD) causing heart attacks remains the largest cause of death, claiming a staggering 28,000 lives a year. Oxidative stress, resulting from increased production of oxygen free radicals in arteries, is an important cause of CHD, heart attacks and strokes. We seek to understand how such oxyradicals are produced in the key cells that form the lining of all arteries, known as the vascular endothelium. By using novel DNA-type molecules (known as anti-sense) develo ....In Australia, coronary heart disease (CHD) causing heart attacks remains the largest cause of death, claiming a staggering 28,000 lives a year. Oxidative stress, resulting from increased production of oxygen free radicals in arteries, is an important cause of CHD, heart attacks and strokes. We seek to understand how such oxyradicals are produced in the key cells that form the lining of all arteries, known as the vascular endothelium. By using novel DNA-type molecules (known as anti-sense) developed in our laboratory, which block a particular gene causing oxidative stress, we will determine whether this gene is responsible for the formation of oxyradicals in human and mouse cells grown in culture. In addition, we will explore whether this gene is turned on by factors known to be involved in CHD. Finally, we will also investigate whether the good cholesterol known as HDL can act to prevent oxidative stress in human cells, as we discovered it appears to do in living arteries in vivo. If we find it has the same protective effect in endothelium, we will determine how it does this, and which component proteins of the HDL particle are important. This might suggest new treatments to prevent acute events leading to heart attack and stroke, and possibly new applications where damage appears to result from acute oxidative stress, such as in the brain soon after a stroke has occurred. We also have a plan to develop antisense drugs that will target the important gene specifically in the affected endothelium. In addition, we have other specific new drugs that will block this system in arteries. Simultaneously we will be testing the role of this gene in mouse and rabbit models of artery disease, for both our types of drugs might provide valuable new therapeutic agents to target the underlying cause of CHD and not just its symptoms as current drugs do.Read moreRead less
Measurement and Prediction of Vulnerable Plaque Formation and Rupture. The major health problem of atherosclerosis, leading to large numbers of deaths from heart attacks and strokes worldwide, will be studied by a multidisciplinary team. Better understanding of how the disease evolves and its earlier detection will arise from this project, which will use synchrotron imaging and supercomputer prediction.
The Persisting Vascular Effects Of Activation Of The Renin-Angiotensin System
Funder
National Health and Medical Research Council
Funding Amount
$628,456.00
Summary
Heart attacks and strokes are the major cause of death and disability in Australians. Heart disease is widely viewed to be the legacy of our diet and lifestyle, and even that of our parents. We propose to explore in detail the molecular mechanism of how this imprinting comes about and identify new targets to prevent, retard or reverse heart disease.
JDRF/NHMRC Diabetes Complications Centre Of Research Excellence
Funder
National Health and Medical Research Council
Funding Amount
$2,607,291.00
Summary
Despite intensive intervention some individuals with type 1 diabetes develop complications. There remains an urgent need for means to identify patients at risk of complications and new targets and therapies for preventing, arresting, treating and reversing them. The primary objective of the Diabetes Complications Centre of Research Excellence (DC-CRE) is to translate novel experimental findings into preventive/treatment strategies for the management of diabetes and its complications.
National Centre Of Research Excellence To Improve Management Of Peripheral Arterial Disease
Funder
National Health and Medical Research Council
Funding Amount
$2,618,637.00
Summary
Approximately 15% of adults have blockages or weakness of major arteries in the periphery, associated with impaired quality of life and a high mortality. Significant management deficiencies for these problems include limited diagnostic, prognostic and treatment options, as well as poor adoption of evidence based practice. The proposed national centre will bring together a group of experts in the field to instigate a number of initiatives to improve patient management.
Biophysical identification of natural human antibody targets. A natural human antibody, PAT-SM6, isolated using technology developed by the partner organisation (Patrys), offers promise as a therapy to reduce mortalities due to cancer, the leading cause of death in Australia. The novelty of the approach pioneered by Patrys is the direct production of human antibodies which avoids undesirable side effects associated with the use of antibodies containing non-human components. This project is to ....Biophysical identification of natural human antibody targets. A natural human antibody, PAT-SM6, isolated using technology developed by the partner organisation (Patrys), offers promise as a therapy to reduce mortalities due to cancer, the leading cause of death in Australia. The novelty of the approach pioneered by Patrys is the direct production of human antibodies which avoids undesirable side effects associated with the use of antibodies containing non-human components. This project is to discover the specificity of PAT-SM6 for proteins and protein complexes and how these interactions lead to tumour cell death. This work will enhance the effectiveness of human antibody therapies and help in the development of this fast growing area within the biotechnology industry in Australia.Read moreRead less
Reducing Disparities In Heart Disease-Related Morbidity And Mortality: Optimising Prevention And Management
Funder
National Health and Medical Research Council
Funding Amount
$826,854.00
Summary
Heart disease contributes to a large but potentially preventable burden of death and disability. This burden is uneven with particularly vulnerable/at risk groups - including those living in regional areas and developing countries, Indigenous Australians and older patients with chronic heart disease. Prof. Simon Stewart will lead national/international collaborations to undertake innovative, multidisciplinary, prevention and disease management programs to reduce the impact and burden of heart di ....Heart disease contributes to a large but potentially preventable burden of death and disability. This burden is uneven with particularly vulnerable/at risk groups - including those living in regional areas and developing countries, Indigenous Australians and older patients with chronic heart disease. Prof. Simon Stewart will lead national/international collaborations to undertake innovative, multidisciplinary, prevention and disease management programs to reduce the impact and burden of heart disease in these vulnerable groups.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE130100537
Funder
Australian Research Council
Funding Amount
$375,000.00
Summary
Neural regulation of immunity following brain injury. Following a brain injury, the brain tries to protect itself by blocking all inflammation. However, this renders the host with impaired immunity and increased risks to infections. The project aims to delineate the mechanisms behind this response, with the expected outcome of highlighting the important interplay between the nervous and immune system.
Improving Health Outcomes In Atrial Fibrillation Via Optimal Management
Funder
National Health and Medical Research Council
Funding Amount
$314,644.00
Summary
Atrial fibrillation (AF; the most common irregular heart beat seen in medical practice) is becoming increasingly more common, costly and deadly in Australia and worldwide, particularly due to population ageing. The goal of this research is to develop 3 patient assessment tools focussing specifically on AF and improving a patient’s ability to care for themself. Overall, the goal is to make patient care more AF focussed and individual and more likely to result in better long-term health benefits.
Which Heart Failure Intervention Is Most Cost Effective In Reducing Hospital Care (WHICH? II) Trial: A Multicentre, Randomised Trial Of Standard Versus Intensified Management Of Metropolitan And Regional-dwelling Patients With Heart Failure
Funder
National Health and Medical Research Council
Funding Amount
$1,891,210.00
Summary
Chronic heart failure (CHF) management programs are now the gold-standard to cost-effectively care for thousands of Australians hospitalised with CHF each year. We’ve shown that home-based management is most cost-effective in reducing hospital stay in CHF. The Which Intervention is most Cost-effective in reducing Hospital care (WHICH? II) Trial, a multicentre, randomised study, will determine if more intensive care (via home visits and remote care contacts) further improves poor outcomes in CHF.