Antiphospholipid Syndrome Related Thrombosis: Understanding The Disease Pathogenic Mechanisms Is The Key To Better Diagnosis And Treatment
Funder
National Health and Medical Research Council
Funding Amount
$607,497.00
Summary
Patients with the Antiphospholipid Syndrome develop thrombosis at a young age. It requires long-term treatment with blood thinning medications, which have risks of severe bleeding. Methods are needed to decide which patients require long term treatment, avoiding unnecessary treatment in low risk patients. Such methods do not currently exist. In this study we explore how useful two novel assays developed by us are in identifying which of these patients are at high risk of thrombosis.
The Role Of Redox-related Post-translational Changes Of Complement Factor H (CFH) In Age-related Macular Degeneration
Funder
National Health and Medical Research Council
Funding Amount
$652,019.00
Summary
Patients with AMD experience loss of central vision and this disorder is the leading cause of blindness in those aged over 50 years in Australia. There are currently no effective treatments for dry AMD. We have identified a protein that undergoes a modification in the blood and the eyes of humans with AMD that has given us new insights into how AMD develops. Specific therapies targeting this modified protein may offer a new treatment for this important cause of blindness.
Therapeutically Targeting The Major Genetic Risk Factor Of Alzheimer’s Disease
Funder
National Health and Medical Research Council
Funding Amount
$530,069.00
Summary
The second greatest risk factor for Alzheimer’s disease (after age) is genetic variation in a protein called APOE, however it is unknown why APOE increases the risk of disease. We have new clinical and laboratory evidence that APOE incresase risk of Alzheimer’s disease by manipulating iron pathways in the brain. We plan to examine these pathways and apply a new theraputic we have developed that targets these pathways in animal models of Alzheimer’s disease.
S100 Proteins: Novel Oxidant Scavengers In Allergic Inflammation
Funder
National Health and Medical Research Council
Funding Amount
$505,814.00
Summary
Allergic inflammation includes conditions such as dermatitis and asthma. Asthma, affects one in 10 adults and one in 6 Australians, costing ~$720 million/annum. We will characterize new mediators of oxidant defence which have suppressive effects on key pathogenic processes. The novel oxidative changes in S100 proteins may lead to new diagnostic reagents and new strategies for therapy. Results will open new frontiers in asthma biology and will apply to other chronic inflammatory diseases.
An Essential Role For Skeletal Muscle FoxO1 In Protecting Against Obesity-induced Insulin Resistance
Funder
National Health and Medical Research Council
Funding Amount
$593,888.00
Summary
Skeletal muscle is the largest organ in the human body and accounts for approximately 80% of glucose disposal after a meal. We have identified a transcription factor, namely FoxO1, that appears protect against obesity-induced insulin resistance by promoting energy consumption. This project will examine whether skeletal muscle specific activation of FoxO1 is a possible therapeutic target for the treatment of obesity-induced insulin resistance.
Novel Interplay Of Oestrogen And Growth Hormone In Regulating Lipid Metabolism
Funder
National Health and Medical Research Council
Funding Amount
$673,045.00
Summary
These studies provide insights into the mechanisms and role of oestrogen in regulating whole body and liver fat metabolism. Oestrogen-related medications that modify the action or tissue availability of oestrogen are widely used therapeutics and can predispose to obesity and fat accumulation in the liver. Whether the effect is direct or through interplay with other metabolic hormones is unknown. This proposal examines their metabolic consequences and impact on obesity and liver health.
Control Of Anabolic And Catabolic Pathways By AMPK
Funder
National Health and Medical Research Council
Funding Amount
$946,402.00
Summary
This project focuses on the role of the metabolic stress-sensing enzyme AMP-activated protein kinase (AMPK) in the control of glucose and fat metabolism. AMPK has been linked to the regulation of exercise capacity, longevity and the control of insulin sensitivity. This is important for our understanding of the metabolic dimensions of our Nations most important health problems including, type-2 diabetes, cardiovascular disease, obesity, neurodegeneration as well as other age onset diseases.
Development Of New Anticancer Drugs Using Sortase-mediated Ligation
Funder
National Health and Medical Research Council
Funding Amount
$618,274.00
Summary
There is a great need for new cancer treatments. We are developing cyclic peptides as the next generation of safe and effective cancer drugs. Cyclic peptides, unlike their linear counterparts, display high stability and oral bioavailability, as well as high solubility and negligible immune response. One of the hurdles is the cyclisation process and we aim to develop enzyme-mediated cyclisation as a convenient and cost effective method for cyclic peptide production.
Role Of AMPK Signaling In Metabolic Control During Exercise
Funder
National Health and Medical Research Council
Funding Amount
$566,288.00
Summary
It is well recognized that sedentary life styles are associated with increased incidence of obesity, Type 2 diabetes and atherosclerotic cardiovascular disease. The medical, social and financial costs of these diseases are growing rapidly and represent a major health care challenge. Exercise is beneficial for maintaining health in patients at risk of developing these diseases and for this reason we are interested in understanding how exercise capacity is regulated.
Does Inhibition Of Myeloperoxidase Attenuate Atherosclerosis?
Funder
National Health and Medical Research Council
Funding Amount
$572,659.00
Summary
This project examines whether inhibition of a protein that produces bleach and is part of the immune system inhibits the stiffening of arteries, i.e. the major cause of cardiovascular disease that leads to heart attack and stroke. The project uses a pharmacological approach, employing a new class of chemical compounds. If successful, the project will contribute to the establishing of a novel therapeutic target to combat cardiovascular disease.