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Formyl Peptide Receptor Biased Agonists As Novel Cardioprotective Agents Against Myocardial Infarction.
Funder
National Health and Medical Research Council
Funding Amount
$318,768.00
Summary
Heart attack and its resulting heart failure are the leading causes of death in Australia. Examining a promising new target (formyl peptide receptors), I will use my knowledge of drug action at the single cell level to identify new drugs that act via a unique biased mechanism. These will be tested in pre-clinical animal models of heart attack to uncover critical new potential therapies that will protect the heart post heart attack and prevent the development heart failure.
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.
Research Fellowship: Protection Of Myocardial Function In Health And Disease
Funder
National Health and Medical Research Council
Funding Amount
$631,010.00
Summary
Heart failure (HF) is a major cause of death in Australia. A/Prof Rebecca Ritchie heads Heart Failure Pharmacology at Baker IDI. Her research focuses on new drug strategies to maintain heart function in response to diabetes & heart attack, common precursors of HF. Many of the treatments discovered from this work are naturally-occurring antioxidants; enhancing their activity will ultimately reduce progression to HF & death in the >3 million Australians affected by these disorders.
Aliskiren: Cardioprotection By Increased Bradykinin Levels?
Funder
National Health and Medical Research Council
Funding Amount
$295,236.00
Summary
Aliskiren is a new treatment for hypertension. Our recent studies indicate that aliskiren may have additional benefits for patients with ischaemic heart disease and heart failure. This research project will investigate the effects of aliskiren in different forms of heart disease in rats, in order to provide information that will help patients obtain the maximum benefit from this treatment.
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.
This project will test whether activators of a novel estrogen receptor (GPER) can limit brain injury and functional deficits after stroke in mice. Part of the work will evaluate two drugs currently in clinical use for chronic conditions – tamoxifen and estradiol – as potential therapies for use in acute stroke. We will study the therapeutic time window of several drugs over up to a week after stroke, and identify key mechanisms underlying the protection by these GPER drugs.
ROLE OF A DOWN SYNDROME-RELATED PROTEIN IN STROKE OUTCOME
Funder
National Health and Medical Research Council
Funding Amount
$931,302.00
Summary
This project will test whether a gene called DSCR1, which is present at a higher level in Down Syndrome individuals, might play a protective role in the outcome after stroke. We will identify the cells and molecular pathways that are involved in this protective effect in mice, with a longer term view of applying this information to the development of new types of targeted therapies for clinical stroke.
Adenosine Receptor Biased Agonism To Treat Ischaemic Heart Disease
Funder
National Health and Medical Research Council
Funding Amount
$682,163.00
Summary
Adenosine A1 receptor (A1R) activation confers powerful protection to heart cells, however clinical application remains suboptimal due to adverse effects such as a slowing in heart rate and decrease in blood pressure. Importantly a new class of compounds, A1R biased agonists, can mediate potent cardioprotection in the absence of adverse effects. This proposal will establish the molecular mechanisms involved and the scope to develop A1R biased agonists as a novel approach to treat heart disease.
Does A Novel Estrogen Receptor Worsen Stroke Outcome?
Funder
National Health and Medical Research Council
Funding Amount
$524,820.00
Summary
This project will test whether a target protein for estrogen, called GPER, which is found in high levels in the brain, worsens stroke outcome. We will identify the key signalling pathways related to GPER in the brain after stroke and we hope to identify a new type of drug that could be used to treat stroke patients. It is possible that our work could at least partly explain why hormone replacement therapy can increase the risk of worsened outcome after stroke in women.
Investigating A Novel Agent To Limit Brain Injury And Post-stroke Complications
Funder
National Health and Medical Research Council
Funding Amount
$412,429.00
Summary
Stroke is a leading cause of morbidity and mortality worldwide, but treatment options remain limited. The goal of this research project will be to examine the potential of new agent to protect the brain against stroke and to also treat complications that typically occur after stroke including infection and weight loss. It is anticipated that this project will ultimately lead to the development of an effective stroke therapy.