Assessment Of Calcium Signaling In Breast Cancer Cells Associated With Epithelial-mesenchymal Transition
Funder
National Health and Medical Research Council
Funding Amount
$116,762.00
Summary
This research will assess the role of specific proteins that control cell function in a process which is important in the spread of cancer cells throughout the body. The work is aimed at identifying new targets for drugs that may be used to prevent or stop the spread of breast cancer cells to other organs such as the brain and liver.
Calcium acts as a signal to control cell processes important in cancer. The entry of calcium into the cell is regulated by calcium channels and we have found some channels are over-expressed in breast cancer. Altering the expression and activity of these calcium channels is a possible therapeutic approach for cancer. We will determine the reasons and consequences of alterations of calcium channels in breast cancer and whether they are viable anti-cancer therapies and biomarkers.
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.
Oxidation Of Arterial Extracellular Matrix By Myeloperoxidase-derived Oxidants
Funder
National Health and Medical Research Council
Funding Amount
$183,266.00
Summary
It is well established that changes occur in the composition and nature of the extracellular matrix present in the artery wall during the development of atherosclerosis. The changes that occur in this matrix affect both the mechanical and physical properties of the arterial wall (e.g. its ability to cope with the high pressures genrated by the pumping of blood from the heart) and the adhesion of cells. It is well established that certain key cell types do not adhere well, or grow properly, on al ....It is well established that changes occur in the composition and nature of the extracellular matrix present in the artery wall during the development of atherosclerosis. The changes that occur in this matrix affect both the mechanical and physical properties of the arterial wall (e.g. its ability to cope with the high pressures genrated by the pumping of blood from the heart) and the adhesion of cells. It is well established that certain key cell types do not adhere well, or grow properly, on altered or damaged matrix and this can result in either the loss of key cell types from the artery wall (e.g. loss of endothelial cells) and - or the proliferation and invasion of cells from other sources (e.g. smooth muscle cell invasion into the intimal space). There is circumstantial evidence that some of these changes occur via the formation of oxidants by the heme enzyme myeloperoxidase which is released from activated white cells. In this study we will employ recently developed analytical techniques to examine the nature of the alterations that are present in atherosclerotic plaques in comparison to normal human artery samples, and investigate the mechanisms by which such alterations arise. We will seek evidence for, or against, the involvement of myeloperoxidase-derived oxidants in the observed changes using specific markers which we have developed for the presence of such damage. This information will allow the rational design of strategies to interfere with the progression of atherosclerosis, which is the major killer of Australians.Read moreRead less
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.
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.