Preclinical Relaxin Therapy To Reverse Cardiac Fibrosis And Gain Functional Benefits
Funder
National Health and Medical Research Council
Funding Amount
$724,754.00
Summary
Cardiac fibrosis is a key factor promoting heart disease and onset of complications including arrhythmias and heart failure. There is urgent and unmet need of drugs that can reverse fibrosis. By documenting anti-fibrotic action of a peptide hormone relaxin, CIA and his team will test therapeutic effect of relaxin in heart disease models focusing on fibrosis-reversal and functional gain, particularly arrhythmias. This work would promote development of relaxin as a new cardiovascular drug.
THE ROLE OF DIFFUSE MYOCARDIAL FIBROSIS IN MYOCARDIAL STIFFNESS
Funder
National Health and Medical Research Council
Funding Amount
$545,126.00
Summary
In many cardiac diseases stiffening of the heart can occur, resulting in worsening symptoms of breathlessness, fatigue and even death. Whilst the exact cause of heart stiffening is not well known, fibrosis of the heart is believed to of prime importance. This research will examine the contribution of fibrosis to heart stiffening, using cardiac magnetic resonance imaging (CMR) as a non-invasive means of assessing heart fibrosis.
Anthracyclines Disrupt Ca2+ Signalling In Cardiomyocytes: A Contribution To Cardiac Toxicity
Funder
National Health and Medical Research Council
Funding Amount
$525,620.00
Summary
Anthracyclines are one of the most effective drugs used in chemotherapy, but cause side effects resulting in serious heart problems which can be fatal. The link between anthracycline therapy and the problems they cause in the heart is not fully defined. We will investigate mechanisms leading to these side effects and define specific targets of anthracyclines in the heart. It is hoped this will lead to the design of new drugs which counteract the side effects of anthracycline treatment.
Using Nkx2-5 Knock-in Mouse Models To Understand Complex Cardiac Diseases
Funder
National Health and Medical Research Council
Funding Amount
$611,340.00
Summary
The most common cause of postnatal mortality is heart defects associated with mutation in transcriptional factors, of which NKX2-5 is the master gene. NKX2-5 is also involved in cardiac dysfunction in adults. We developed a unique mouse genetic approach that mimics human disease to study the mechanism behind this gene function. Our work paves the way to more efficient forecast, counseling and treatment strategies, reducing the socio-economic burden of congenital heart disease our community.
Phospholipase Cbeta 1b, A Target To Limit Atrial Dilatation
Funder
National Health and Medical Research Council
Funding Amount
$544,847.00
Summary
We have identified a heart specific protein that is involved in perpetuating dilatation of the upper chambers of the heart and thereby contributing to cardiac disease. Inhibitors of this protein provide a suitable target for therapy to limit heart disease. The current studies aim to test such inhibitors in vivo as proof-of-concept that such treatment effectively limits cardiac dysfunction.
Valvular heart disease is a common cause of heart failure. Identification of the genetic causes of valvular heart disease has important implications in our understanding of these heart diseases, as well as translating these genetic discoveries into better diagnostic and prevention strategies in at-risk families. This research proposal seeks to perform a comprehensive clinical and genetic investigation of individuals and families with the two most common valvular heart diseases, mitral valve prol ....Valvular heart disease is a common cause of heart failure. Identification of the genetic causes of valvular heart disease has important implications in our understanding of these heart diseases, as well as translating these genetic discoveries into better diagnostic and prevention strategies in at-risk families. This research proposal seeks to perform a comprehensive clinical and genetic investigation of individuals and families with the two most common valvular heart diseases, mitral valve prolapse and congenital bicuspid aortic valve.Read moreRead less
How Does Chronic Epilepsy Result In Cardiac Electrophysiological Dysfunction?
Funder
National Health and Medical Research Council
Funding Amount
$737,112.00
Summary
Cardiac dysfunction is common in epilepsy, and could be an important contributor to the increased risk of sudden death in people with epilepsy (SUDEP). In this grant we will investigate: when changes in the cardiac function develop in relation to the epilepsy; if people with chronic epilepsy have similar changes; and what effect seizures and epilepsy has on the nerves innervating the heart. The outcomes have the potential to motivate new treatments and prevention for this important problem.
Early Detection Of Chemotherapy-related Cardiotoxicity
Funder
National Health and Medical Research Council
Funding Amount
$269,401.00
Summary
This project examines myocardial dysfunction in breast cancer patients treated with anthracycline chemotherapy. Chemotherapy related cardiotoxicity is often asymptomatic until significant cardiac dysfunction occurs. Cardiac function is evaluated by LV ejection fraction (LVEF), which is a coarse measure of cardiac function. Strain analysis measure myocardial deformation and is more sensitive to subclinical cardiac dysfunction, and demonstrates alterations prior to the development of reduced LVEF.
Local Sleep In The Awake Brain: An Underlying Cause Of Neurobehavioural Deficits In Sleep Apnea?
Funder
National Health and Medical Research Council
Funding Amount
$582,330.00
Summary
Obstructive sleep apnea (OSA) is a common sleep disorder which significantly impacts daytime functioning leading to excessive sleepiness, and problems with attention and thinking. Currently, the causes for cognitive impairment in OSA (including attentional lapses and performance deficits) are poorly understood. In the awake state, groups of neurons can briefly go “offline” as they do in sleep. These periods of “local sleep” may explain impaired task performance in OSA.
Regulation Of RyR2 Channels By Calmodulin In Healthy And Diseased Hearts
Funder
National Health and Medical Research Council
Funding Amount
$614,421.00
Summary
In the heart, RyR2 is responsible for intracellular Ca2+ release. The RyR2 is comprised of a Ca2+ channel and accessory proteins such as CaM that regulate channel activity. Evidence suggests that RyR2 regulation by CaM is altered in heart failure and human arrhythmia syndromes, but there has been no direct evidence for this. We will provide this direct evidence plus determine how CaM regulates RyR2 channels and intracellular Ca2+ release and how this leads to cardiac arrhythmias.