This research is directed by a team of medical and basic scientists with expertise in mechanisms of inflammation relevant to human disease. The program will investigate the molecular and cellular events that are responsible for inflammation in the kidneys, joints and blood vessels which lead to diseases such as glomerulonephritis, arthritis and atherosclerosis. The aim of the research is to find new therapeutic targets which may be specific to certain organs or disease processes, in order to dev ....This research is directed by a team of medical and basic scientists with expertise in mechanisms of inflammation relevant to human disease. The program will investigate the molecular and cellular events that are responsible for inflammation in the kidneys, joints and blood vessels which lead to diseases such as glomerulonephritis, arthritis and atherosclerosis. The aim of the research is to find new therapeutic targets which may be specific to certain organs or disease processes, in order to develop more effective and selective treatments ofchronic inflammatory disease in humans.Read moreRead less
Platelet Glycoprotein Proteolysis: Novel Mechanisms And Risk Factors
Funder
National Health and Medical Research Council
Funding Amount
$441,473.00
Summary
Platelets are the richest source of amyloid precursor protein (APP) in the body. Platelet ADAM10 regulates both the expression and function of the major platelet collagen receptor GPVI, and protective APP processing. Coagulation protein Factor X has a role in activation of ADAM10. This activation is disrupted in blood that has been treated with direct oral anticoagulant (DOAC) rivaroxaban. This grant will investigate the implications for people taking rivaroxaban on regulation of APP and GPVI.
Structural And Functional Studies On The Interaction Between Alpha2-Antiplasmin And Plasmin
Funder
National Health and Medical Research Council
Funding Amount
$280,400.00
Summary
Fibrinolysis is the process by which the body dissolves clots. In this proposal we aim to investigate how the fibrinolysis inhibitor alpha2-antiplasmin interacts with the clot dissolving protease enzyme plasmin. These data will be useful for developing new approaches to accelerate plasmin-mediated clot breakdown.
This program of research is firmly focussed on the basic mechanisms involved in normal functioning of cells and tissues, followed by a step by step process to understand the abnormal or the diseased. The disease states we are investigating involve the blood and blood vessels, and when there is malfunction it may contribute to conditions as diverse as atherosclerosis, thrombosis, inflammation and cancer. The program thus addresses the fundamentals of diseases which are responsible for most deaths ....This program of research is firmly focussed on the basic mechanisms involved in normal functioning of cells and tissues, followed by a step by step process to understand the abnormal or the diseased. The disease states we are investigating involve the blood and blood vessels, and when there is malfunction it may contribute to conditions as diverse as atherosclerosis, thrombosis, inflammation and cancer. The program thus addresses the fundamentals of diseases which are responsible for most deaths in our society. We will use technology which is proven to provide precise information, the molecular and biochemical processes responsible for cell function (or malfunction). However in each individual project there will be a clear path to a clinical use, diagnostic or therapeutic. Indeed in a number of the components of the program there are already potential treatments and diagnostics in development and trial.Read moreRead less
Does Fresh Frozen Plasma In Russells Viper Bite Coagulopathy Reduce The Dose And Duration Of Antivenom Therapy?
Funder
National Health and Medical Research Council
Funding Amount
$622,344.00
Summary
This proposal seeks funding to undertake a trial of clotting factor replacement with low dose antivenom therapy in snake bite coagulopathy in Sri Lanka. The aim is to determine if factor replacement will result in a rapid return of clotting function, allow a smaller dose of antivenom and therefore reduce the potential risk of major bleeding and reactions to antivenom. This study will have international implications because globally snakebite coagulopathy is a major cause of morbidity and death .
Sympathetic Control Of Cutaneous Blood Flow And Blood Pressure In Human Spinal Cord Injury
Funder
National Health and Medical Research Council
Funding Amount
$242,002.00
Summary
While spinal cord injury can cause devastating changes in the nervous system paralysis and loss of sensation relatively little is known about changes to the sympathetic nervous system. The sympathetic nervous system is intimately involved in the ongoing control of blood pressure, blood flow and temperature control. Loss of sympathetic control can occur following spinal cord injury. Interruption of descending pathways can result in partial or complete loss of sympathetic outflow from the thoracol ....While spinal cord injury can cause devastating changes in the nervous system paralysis and loss of sensation relatively little is known about changes to the sympathetic nervous system. The sympathetic nervous system is intimately involved in the ongoing control of blood pressure, blood flow and temperature control. Loss of sympathetic control can occur following spinal cord injury. Interruption of descending pathways can result in partial or complete loss of sympathetic outflow from the thoracolumbar segments. Complete decentralization can result in autonomic dysreflexia (autonomic hyperreflexia), in which sensory stimuli originating below the lesion evoke a reflex increase in sympathetic drive to the blood vessels, causing them to constrict. Because of this, blood pressure may rise suddenly and remain at such high levels that stroke and (occassionally) cardiac arrest may occur. This phenomenon, autonomic dysreflexia, is considered a medical emergency. The typical subjective signs of autonomic dysreflexia include a throbbing headache, tingling in the head or nasal congestion; sweating and flushing above the lesion are clinical signs that prompt medical staff to measure blood pressure and to locate the source of sensory irritation (usually a distended bladder or impacted colon, sometimes a pressure sore or ingrown toenail). Commonly, however, subclinical episodes go undetected, and this phenomenon of silent dysreflexia is of increasing concern. This project will develop means of assessing the integrity and state of the sympathetic nervous system below a lesion in patients with spinal cord injury and characterize the firing properties of reflexly activated sympathetic neurones.Read moreRead less
Role Of Resident Endothelial Progenitor Cells In Melanoma Vascularisation And Progression
Funder
National Health and Medical Research Council
Funding Amount
$952,328.00
Summary
Melanoma is one of the most frequent cancers in Australia. Its growth depends on the rpoper delivery of nutrients and oxygen through blood vessels. This requires the formation of new blood vessels as the tumour grows. In this project we intend to understand the origin of the blood vessels that form in tumours and identify the stem cells that support them. We will use proof of principle experiments to determine whether removal of these stem cells allows the regression of melanoma tumours.
Characterisation Of Human Embryonic Stem Cell Differentiation To Haematopoietic Progenitors And Stem Cells
Funder
National Health and Medical Research Council
Funding Amount
$638,856.00
Summary
Blood stem cells, which are found in the bone marrow, are currently used for treating human blood disorders including leukemia and lymphoma. However, for the majority of bone marrow transplant candidates, suitable donors cannot be found. Using embryonic stem cells, this project aims to define the conditions required to generate blood stem cells in the laboratory. The aim of the work is to provide a new source of blood stem cells that could be used in place of donor derived bone marrow.