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Airway Smooth Muscle And Fixed Airway Obstruction: Strategies For Softening Muscle
Funder
National Health and Medical Research Council
Funding Amount
$555,643.00
Summary
In severe asthma the airways don't relax fully making breathing more difficult. The inability to relax is being addressed by exploring the behaviour of isolated muscle cells. These cells are able to compact collagen gels. The mechanisms used to compact the gel are different to those that cause rapid muscular contraction. We aim to identify the molecules responsible for the gel compaction as a first step to identifying new drugs to treat the fixed airway obstruction in severe asthma.
Understanding Uterine Contractility: What Can We Learn From Obesity?
Funder
National Health and Medical Research Council
Funding Amount
$600,792.00
Summary
The incidence of failure to progress in labour has increased in recent years, being linked to the rise in obesity. The result is a significant escalation in the rate of delivery by Caesarean Section (CS) which increases the risk of serious complications during subsequent pregnancies. We have identified five dysfunctional systems associated with poor uterine contraction. We now aim to determine the mechanisms underlying these dysfunctional systems, particularly those mechanisms in common.
Targeting Small Airways To Overcome Resistance To Therapy In Asthma
Funder
National Health and Medical Research Council
Funding Amount
$531,045.00
Summary
There is a pressing need to overcome resistance to current therapies for severe asthma. Targetting inflammation-induced changes in small airway contraction offers an alternative strategy. We have identified a novel bronchodilator that relaxes maximally contracted mouse small airways when current treatment is ineffective. We will demonstrate its efficacy in animal models mimicking key features of human asthma, and define new ways to improve outcomes in poorly-controlled asthma.
Are Novel Nitric Oxide Mimetics Protective In Vascular Disease?
Funder
National Health and Medical Research Council
Funding Amount
$634,044.00
Summary
Nitric oxide (NO) is a biologically active gas which controls blood flow and blood pressure. New drugs which mimic the effects of NO show promise in the treatment of cardiovascular disease. This study investigates the ability of NO mimetics to protect blood vessels in disease, by limiting the production of toxic molecules, improving blood flow and preventing blood clot formation. The information gained may lead to the development of new therapies for blood vessel diseases such as stroke.
Stroke is a devastating disease causing mortality and morbidity on a massive scale, and which still has no treatment besides a clot-buster that cannot be used in 90% of patients. This research should provide a better understanding of stroke pathology and identify new therapeutic directions. It will elucidate an unappreciated but crucial role of specific immune cells in brain injury after stroke, and hopefully lead to new ways to limit brain injury and promote recovery from stroke.
M2 Macrophage Polarization As A Cause Of Vascular Fibrosis And Stiffening In Hypertension
Funder
National Health and Medical Research Council
Funding Amount
$657,028.00
Summary
Blood vessel stiffening is a hallmark of hypertension (A.K.A. high blood pressure) and is thought to be a major contributor to the clinical complications of the condition, which include heart failure, stroke and renal impairment. Here we will test the novel concept that this stiffening process is caused by certain types of white blood cells (macrophages), which enter the walls of blood vessels and signal the surrounding cells to produce a rigid scaffolding protein called collagen.
Improving Endothelial Dysfunction In Diabetes-associated Vascular Diseases With Nrf2 Activators
Funder
National Health and Medical Research Council
Funding Amount
$340,039.00
Summary
Diabetic patients have a greater risk of developing cardiovascular diseases as compared to the general population. This is largely attributed to the impact the diabetic environment has on the endothelium (inner layer of the blood vessel). Indeed, clinical studies have shown that impaired endothelial function occurs prior to the development of cardiovascular diseases. Hence, we propose to study a novel way to improve endothelial function by limiting oxidative stress and inflammatory pathways.
Pharmacological Inhibition Of IRAP As A Novel Antifibrotic Strategy
Funder
National Health and Medical Research Council
Funding Amount
$1,036,370.00
Summary
There are very few treatments that can reduce heart stiffening, called fibrosis, which is seen in patients with high blood pressure or in patients who have had a heart attack. This project will test new drugs that we have developed that act by a unique mechanism to reverse or prevent cardiovascular disease in patients with poorly-functioning hearts and blood vessels.
Therapeutic Approaches To Circumvent NO• Resistance In The Type 2 Diabetic Heart And Vasculature
Funder
National Health and Medical Research Council
Funding Amount
$563,337.00
Summary
Type 2 diabetes (T2D) is Australia’s fastest growing chronic disease, affecting almost 2 million Australians (who face poor cardiovascular health outcomes). We have discovered an exciting new avenue that may potentially more effectively counteract heart and blood vessel disorders in T2D patients in an acute cardiovascular emergency, of substantial clinical importance.