Human RIPC-derived Regulatory Molecules For Cardioprotection Against Ischemic And Cardiopulmonary Bypass Injury
Funder
National Health and Medical Research Council
Funding Amount
$642,083.00
Summary
Our previous work indicates that evoked human blood borne factors confer protection against injury, due to loss of blood flow in heart muscle, when a brief stress is remotely applied to a limb (remote ischemic preconditioning). We have identified these proteins that appear to activate genetic and metabolic regulation of adaptive cell survival processes. We will now test their individual and combined capacity, efficiency and mechanisms of protection in the heart using cell and clinical models.
ASIC1a, A New Therapeutic Drug Target For Cardiac Ischemia
Funder
National Health and Medical Research Council
Funding Amount
$1,382,224.00
Summary
Cardiovascular disease is the biggest killer in the world, in large part due to the lack of drugs to protect the heart from the damage caused by injuries such as heart attack. Our team of world-leading scientists and clinicians has identified a novel therapeutic target (ASIC1a) against which drugs could be targeted to protect the heart against these injuries. The aim of this project is to develop novel cardioprotective drugs that target ASIC1a so we can test them in human clinical trials.
Prevention Of Heart Damage During Anthracycline Cancer Chemotherapy
Funder
National Health and Medical Research Council
Funding Amount
$327,214.00
Summary
Doxorubicin is an effective medicine widely used for the treatment of cancer. However, it can cause heart damage, which not only creates a new health problem, but also limits the length of doxorubicin treatment cancer patients can receive, and therefore the likelihood of cancer cure. Preventing heart damage by doxorubicin is therefore important to improve overall cancer cure rates and patient health. This study aims to develop new medications to prevent heart damage during cancer chemotherapy.
Annexin-A1 Agonists Rescue Cardiac Contractile Function After Myocardial Infarction
Funder
National Health and Medical Research Council
Funding Amount
$621,419.00
Summary
Myocardial infarction (or heart attack, a result of reduced coronary blood flow) and subsequent heart failure are the major cause of death in Western societies; this is expanding to all corners of the globe. New treatments for heart attack are thus essential. We have discovered that the natural hormone annexin-A1 rescues heart muscle function over the short-term, and propose that drugs based on annexin-A1 will prevent cardiac dysfunction of heart muscle up to several weeks after heart attack.
Cellular Metabolism And Signalling In Cardiac Development And Congenital Disease
Funder
National Health and Medical Research Council
Funding Amount
$151,061.00
Summary
This project aims to investigate how the paediatric heart responds to oxidative cellular stresses during cardiac development, surgical stress and congenital heart disease. Pre-surgical interventions aims at improving cardiac function following surgery will be examined, with cellular models being used to determine molecular pathways of cardioprotection, as well as testing agents which may limit cellular damage under surgical stress and disease.
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.
Formyl Peptide Receptor Biased Agonists As Novel Cardioprotection From Myocardial Infarction
Funder
National Health and Medical Research Council
Funding Amount
$948,291.00
Summary
Heart attack is caused by a blocked heart blood vessel. Current therapy focuses on rapid reopening of the vessel, to allow blood supply to return. However, even if this is successful, affected patients are often left with impaired heart muscle pumping function, ultimately progressing to heart failure. We have discovered an exciting new mechanism to protect heart muscle from injury and preserve its function, and we plan to develop new drugs for heart attack based on this mechanism.