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.
Ryanodine Receptor Inhibitors As Therapy For Ca2+ Store Overload Induced Arrhythmias
Funder
National Health and Medical Research Council
Funding Amount
$555,892.00
Summary
This study investigates a new therapeutic action recently discovered for flecainide, an antiarrhythmic agent that we find to completely prevent and inherited form of stress-induced arrhythmias called CPVT. The findings will provide the first detailed mechanistic understanding of an antiarrhythmic drug, findings that will also give a new direction for drug design to control common arrhythmias such as occur in diseases such as coronary artery disease.
CCR4/NOT Complex Is A Conserved Regulator Of Heart Function
Funder
National Health and Medical Research Council
Funding Amount
$467,567.00
Summary
Cardiovascular diseases kill an Australian every 11 minutes. The goal of this proposal is to characterize the role of the conserved heart regulators in cardiac function and disease. Our combined multi-species and informatics approach has identified a major disease locus for sudden cardiac death in humans, which we propose to characterize. This work can lead to new classes of drugs to improve cardiac health and also aid in early diagnosis of patients susceptible to sudden cardiac death.
Targeting Lipids Regulated In A Setting Of Physiological Cardiac Hypertrophy
Funder
National Health and Medical Research Council
Funding Amount
$489,970.00
Summary
Existing heart failure therapies largely delay heart failure progression rather than reversing the disease. New therapeutic strategies with the ability of improving function of the failing heart are thus greatly needed. The primary goal of this study is to determine whether lipids that are secreted by the heart in a setting of “good” physiological heart growth (as occurs with exercise) can be targeted to restore function of the failing heart.
New Gene Discovery In Familial Hypertrophic Cardiomyopathy
Funder
National Health and Medical Research Council
Funding Amount
$418,493.00
Summary
Familial hypertrophic cardiomyopathy is a genetic heart disorder which affects 1 in 500 of the population, and can lead to heart failure and sudden death. Identification of the genetic causes of hypertrophic cardiomyopathy has important implications for our understanding of this disease, and in 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 pe ....Familial hypertrophic cardiomyopathy is a genetic heart disorder which affects 1 in 500 of the population, and can lead to heart failure and sudden death. Identification of the genetic causes of hypertrophic cardiomyopathy has important implications for our understanding of this disease, and in 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 people with familial hypertrophic cardiomyopathy.Read moreRead less
Regulation Of Endogenous Heart Regeneration By An Anti-fibrotic MicroRNA.
Funder
National Health and Medical Research Council
Funding Amount
$440,949.00
Summary
In contrast to the adult heart, the newborn heart undergoes scarless healing following a heart attack. The molecular mechanisms that govern heart regeneration in newborn mammals are not fully understood. The goal of the current study is to determine the role of a recently identified family of molecules known as microRNAs in the regulation of scarless healing. We propose a novel strategy for re-activation of microRNAs in the adult heart to promote regeneration following heart attack.
Regulating Gene Expression Changes In Cardiac Hypertrophy
Funder
National Health and Medical Research Council
Funding Amount
$690,754.00
Summary
Following the success in decoding human genome, i.e. DNA sequence, a major task is to understand how the activity of genes with consequent changes in respective proteins. As proteins are an important component for cell structure and function, such changes in quantity and quality of proteins will play a pivotal role to affect disease development and progression.
Preclinical Assessment Of Gene Therapy For Ventricular Arrhythmia
Funder
National Health and Medical Research Council
Funding Amount
$801,079.00
Summary
Up to 10% of patients are at risk of sudden death following myocardial infarction. Current treatment and preventative initiatives have their limits and are not without risk. In this proposal we will continue to develop an exciting new treatment approach using gene therapy technology. We will attempt to overcome some of the barriers for human application of this technology and pave the way for early phase clinical trials.
New Cardiac Ryanodine Receptor Inhibitors For The Treatment Of Heart Failure
Funder
National Health and Medical Research Council
Funding Amount
$612,885.00
Summary
We have discovered that a protein that is recognized for its role in phase II detoxification can also modify the calcium signaling that underlies heart function. The small part of the protein that is active in heart tissue differs from the enzyme center that supports detoxification and can thus be used as a therapeutic agent in heart failure and in genetic cardiac conditions. The project is to develop the cardio-active part of the protein for maximum efficacy and for eventual clinical use.
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.