We aim to grow body tissues for surgery, including heart muscle, liver and pancreatic islets (for diabetes) and will investigate using stem cells to repair the brain after stroke. We will attempt to boost the expansion of blood vessels in growing tissues using molecular tools we have found crucial for cell signaling. In growing heart tissues and in stroke we will improve drugs that might boost the potential of stem cells to regenerate damaged tissues
Cytoprotective And Metabolic Responses To Biased Agonists Acting At Cardiomyocyte Gq-coupled Receptors
Funder
National Health and Medical Research Council
Funding Amount
$723,742.00
Summary
Cell surface receptors mediate the response of cardiac muscle cells to hormones and transmitters by interacting with a repertoire of intracellular signalling proteins. Despite primary coupling to Gq proteins that activate shared pathways, four such receptors promote differing responses in cardiac cells. We will investigate signalling pathways differentially activated by the ?1A-adrenergic receptor that promote survival of cardiac muscle under conditions of cell damage or nutrient insufficiency.
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.
Targeting Aldosterone Receptors In Cerebrovascular Disease
Funder
National Health and Medical Research Council
Funding Amount
$857,712.00
Summary
Stroke represents a major health (accounting for 6% of all deaths) and economic (costs Australia $2.14 billion per year) burden on society, thus clearly more effective treatments are needed. This project will investigate the role of two substances produced in the body – angiotensin II and aldosterone – in stroke outcome, and whether targeting their receptor(s) may prevent poor outcomes following 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.
Better Targets And Drugs For Improving Stroke Outcome?
Funder
National Health and Medical Research Council
Funding Amount
$1,085,972.00
Summary
Infection is highly prevalent and is one of the leading causes of death in stroke. It is now recognised that stroke impairs the immune system, raising the possibility that reversing this impairment can decrease the rate of infection after stroke. Therefore, the focus of this project is to identify the signalling pathways that underlie abnormal immune function after stroke and also assess the potential of a novel pharmacological approach for reducing bacterial infection in stroke patients.
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.
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.