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.
Calcium Signaling And Epithelial-mesenchymal Transition: A New Approach To Identifying Pharmacological Targets For Metastasis
Funder
National Health and Medical Research Council
Funding Amount
$561,645.00
Summary
The largest killer of women with breast cancer is disease that has spread e.g. to brain, bones, lungs. Once breast cancer has spread in this way to secondary sites, also known as metastatic disease, then there is limited treatment available and generally therapy is palliative only. Our work describes experiments that will help us understand the process of metastasis and provide new avenues for drug discovery in metastatic disease, thus helping women who have a poor prognosis.
Interactions Between H5N1 And The Respiratory Epithelium
Funder
National Health and Medical Research Council
Funding Amount
$623,065.00
Summary
This project examines the hypothesis that the severity of H5N1 infection is due to activation of signalling pathways in the lung not activated by human influenza and leads to fluid accumulation in the lungs death of respiratory cells. This study will improve our understanding of influenza infection and identify targets for treatment of H5N1.
New CaMKII Therapeutic Targets In Heart Failure With Preserved Ejection Fraction
Funder
National Health and Medical Research Council
Funding Amount
$740,335.00
Summary
Deaths associated with impaired heart muscle relaxation and unstable cardiac cycle rhythm are increasing. The mechanisms by which these pathologies occur are not understood and clinical therapies are lacking. We have novel evidence to suggest that a key signalling protein, CaMKII, is critically involved in the development of these forms of heart pathology. This goal of this project is to identify how CaMKII is implicated in heart failure and dysrhythmia as a basis for designing new therapies.
Optimising Efficacy Of A Peptide Derived Against The Alpha-interacting Domain Of The L-type Calcium Channel In Reduction Of Ischemia-reperfusion Injury
Funder
National Health and Medical Research Council
Funding Amount
$405,063.00
Summary
A heart attack is associated with an increase in free radicals and calcium in heart muscle cells. The function of the L-type calcium channel, a protein responsible for calcium entry into cells, is altered by free radicals and this contributes to the development of heart disease. We now have considerable proof of concept that a peptide derived against the L-type calcium channel can decrease heart injury. We will optimise efficacy and delivery of the peptide to prevent heart failure.
Optimising Combinations Of Calcium Channel Inhibitors For Treatment Of Secondary Degeneration After Neurotrauma
Funder
National Health and Medical Research Council
Funding Amount
$679,772.00
Summary
Traumatic injury to the central nervous system is made worse by damage that spreads away from the initial point of impact. Excess calcium entering cells is a key contributor to spreading damage but treatment with single calcium channel inhibitors has been disappointing. We will use combinations of calcium channel inhibitors to block multiple calcium channels and ensure the optimised combination is effective in clinically relevant models of neurotrauma.
The Role Of TRPM2 Channels In Oxidative Stress-induced Liver Damage
Funder
National Health and Medical Research Council
Funding Amount
$576,265.00
Summary
Oxidative stress plays a central role in liver injury induced by drug toxicity, ischemia-reperfusion, non-alcoholic fatty liver disease and viral hepatitis. A hallmark feature of oxidative-stress mediated hepatocellular death is Ca2+ and Na+ overload which suggest activation of ion channels on the plasma membrane. This project will investigate the role of Transient Receptor Potential Melastatine 2 (TRPM2) non-selective channels in oxidative stress-induced hepatocellular death.
Exploiting The Overexpression Of A Specific Calcium Permeable Ion Channel In Breast Cancer Cells: A New Pharmacological Approach To Targeting Breast Cancer.
Funder
National Health and Medical Research Council
Funding Amount
$577,717.00
Summary
We have identified that a specific protein that controls the entry of calcium into cells is found at much higher levels in some breast cancer cells. We have also identified that drugs that control the activity of this protein can promote the death of some breast cancer cells. This grant will help further define the mechanism of this effect and determine the applicability of this approach as a therapy for some women with breast cancer.
Novel Analgesic Approaches: Harnessing Functional Interactions Between Sodium Channels And Opioids
Funder
National Health and Medical Research Council
Funding Amount
$329,076.00
Summary
Chronic pain is a debilitating condition that affects the life of one five Australians and has significant socioeconomic impact. Currently available pain killers often do not work, or have intolerable side effects. We have discovered that combination treatment with opioids and a novel venom-derived compound discovered by us provides effective pain relief. The aim of this project is to understand the mechanisms underlying this synergistic effect to develop new treatment approaches for pain.
Identifying The Site/s Of Modification On The Human L-type Ca2+ Channel Protein Isoforms During Oxidative Stress With Reference To Development Of A Therapeutic Target
Funder
National Health and Medical Research Council
Funding Amount
$360,369.00
Summary
A rise in calcium and free radicals in the heart are associated with the development of heart disease. We have good evidence that a protein in the heart muscle known as the L-type calcium channel mediates changes in calcium in response to free radicals. This proposal will identify how the channel function is altered by free radicals so that a therapeutic target can be designed to prevent altered channel function and development of heart disease during increases in free radicals.