Targeting Necroptosis Signalling To Counter Stroke-induced Brain Injury
Funder
National Health and Medical Research Council
Funding Amount
$605,809.00
Summary
The origins of the brain injury that arises from stroke remain a matter of enormous interest. Our work suggests that a poorly understood form of cell death, termed necroptosis, contributes to injury to the brain following stroke. In addition to developing an advanced understanding of this process, we will use drugs developed at the Walter and Eliza Hall Institute to test whether blocking this process might be a plausible therapeutic strategy in stroke patients.
Stem Cell Treatment For Neonatal Hypoxic Ischaemic Encephalopathy
Funder
National Health and Medical Research Council
Funding Amount
$954,195.00
Summary
Hypoxic-ischaemic encephalopathy occurs when the fetus receives inadequate oxygen in labour and many babies die or have brain damage. Stem cell therapy might save these babies from brain damage but there are many unknowns, such as which stem cells to use and how many. Through our skills in stem cells and measuring the rescued brain following injury, we will determine the necessary details for the most effective stem cell therapy to be ready to immediately test the treatment in a RCT in babies.
Gamma-Secretase Inhibitors As Novel Pharmacological Agents To Target Stroke-induced Brain Injury
Funder
National Health and Medical Research Council
Funding Amount
$441,511.00
Summary
Stroke is the world�s 2nd leading cause of death. In Australia, stroke is the leading cause of serious, long-term disability. Alarmingly, there is a looming stroke epidemic in Australia. There is an urgent need for novel therapies capable of reducing mortality and long-term disability in victims of stroke. We have recently identified gamma-secretase inhibitors (GSIs) as a potent stroke therapy. This project will investigate how GSIs protect against ischaemic stroke at the molecular level.
I am a neuroscientist using robust statistical methods to identify effective neuroprotectants for stroke. I am examining the use of neuroprotection and novel imaging approaches to extend the utility of thrombolysis, and testing the hypothesis that neuropr
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.
Superoxide And The Nitric Oxide-peroxynitrite Pathway In Renal Ischaemia-reperfusion Injury
Funder
National Health and Medical Research Council
Funding Amount
$202,755.00
Summary
Acute renal failure is common and has 50% mortality. Free radicals are vey reactive, unstable molecules that alter normal metabolic reactions. The study aims to determine the role of oxygen-derived free radicals and nitric oxide and their interaction in renal ischaemic injury. The balance between the positive effects of nitric oxide on blood flow and the damaging effects of by-products of the reaction of nitric oxide with superoxide radical (peroxynitrite) on renal tubules may determine the exte ....Acute renal failure is common and has 50% mortality. Free radicals are vey reactive, unstable molecules that alter normal metabolic reactions. The study aims to determine the role of oxygen-derived free radicals and nitric oxide and their interaction in renal ischaemic injury. The balance between the positive effects of nitric oxide on blood flow and the damaging effects of by-products of the reaction of nitric oxide with superoxide radical (peroxynitrite) on renal tubules may determine the extent of cell damage and hence recovery from ischaemic and hypoxic renal injury. Modulation of these opposing forces may lead to strategies to protect and improve renal function in acute renal failure in man.Read moreRead less
HYPOXIA AND THE TRANSCRIPTIONAL REGULATION OF CYP GENES IN CELLS
Funder
National Health and Medical Research Council
Funding Amount
$211,527.00
Summary
Hypoxia, or oxygen deprivation caused by the decreased supply of blood to cells, is a component of ischaemic injury of the cardiovascular system (as in angina or atherosclerosis) and numerous other organs (e.g. in cancer and chemical-mediated injury). It is now known that the content of certain proteins that activate specialised target genes is increased rapidly in cells in response to oxygen deprivation. Some of the most important of these proteins are hypoxia-inducible factor-1 (or HIF-1) and ....Hypoxia, or oxygen deprivation caused by the decreased supply of blood to cells, is a component of ischaemic injury of the cardiovascular system (as in angina or atherosclerosis) and numerous other organs (e.g. in cancer and chemical-mediated injury). It is now known that the content of certain proteins that activate specialised target genes is increased rapidly in cells in response to oxygen deprivation. Some of the most important of these proteins are hypoxia-inducible factor-1 (or HIF-1) and activator protein-1 (or AP-1). We have identified a novel target gene that is activated in hypoxia. This gene produces an enzyme, termed cytochrome P450 2J2, that acts on fatty acids which are present in cell membranes and converts them into molecules that control the flow of potassium and calcium ions into cells. Alterations in the flow of such ions into cells have been observed previously in hypoxia but the mechanism of this effect is unclear. Thus, cytochrome P450 2J2 is switched on in hypoxia and generates fatty acid metabolites that control protective ion fluxes in cells.Read moreRead less