Regulation Of Receptors That Control Platelet Function Under Shear Stress
Funder
National Health and Medical Research Council
Funding Amount
$507,273.00
Summary
Specialized human blood cells that control blood loss and clotting (platelets) are currently difficult to test in the clinical laboratory, meaning patients are at risk of excessive bleeding or serious clot formation during disease or treatment. The aim of this proposal is to use our new reagents and assays to develop more reliable methods for evaluating relative bleeding or clotting risk in individuals.
Autoimmune-based thrombocytopenia can be a life-threatening adverse event associated with viral load, surgery, drug therapies or the use of the anticoagulant, heparin. This grant will define mechanisms of anti-platelet antibody-dependent platelet activation and assess shedding of platelet-specific glycoprotein (GP)VI as an immediate consequence of this activation, provide a new strategy for evaluating risk of thrombosis in HIT.
Platelets are key blood elements that are essential for the prevention of bleeding in response to injury or infection. Overactive or spontaneously active platelets cause thrombosis and blood clot formation. My laboratory has identified new physiological pathways of activation of platelet metalloproteinases, the enzymes that regulate surface levels of the prothrombotic platelet receptors. By understanding this mechanism of receptor regulation, we can uniquely target platelet receptors in people w ....Platelets are key blood elements that are essential for the prevention of bleeding in response to injury or infection. Overactive or spontaneously active platelets cause thrombosis and blood clot formation. My laboratory has identified new physiological pathways of activation of platelet metalloproteinases, the enzymes that regulate surface levels of the prothrombotic platelet receptors. By understanding this mechanism of receptor regulation, we can uniquely target platelet receptors in people with prothrombotic pathologies.Read moreRead less
The Role Of Duffy And PF4 In The Platelet Killing Of Malaria Parasites.
Funder
National Health and Medical Research Council
Funding Amount
$350,045.00
Summary
Platelets in the blood can kill the Plasmodium parasite, which lives inside red blood cells and causes malaria. Platelets bind parasite-infected red cells and release a molecule that is toxic to the parasite. This project will study why a red cell molecule called Duffy is also needed for this function of platelets. Most Africans carry a gene for Duffy that stops its expression in red cells, and may therefore be more susceptible to malaria because their platelets cannot kill the malaria parasite.
Mechanisms And Therapies In Cardiovascular Disease
Funder
National Health and Medical Research Council
Funding Amount
$8,360,700.00
Summary
Cardiovascular disease (CVD) claims 1 person every 10 min in Australia and causes 1 in 3 deaths worldwide. The molecular and cellular processes underlying atherosclerosis, vascular injury and thrombosis are highly complex and not well understood. A multifaceted approach is needed to effectively address these key challenges. This Program brings together world experts in these areas to interrogate gaps in our basic understanding of CVD, and to develop novel therapies for CVD patients by exploiting ....Cardiovascular disease (CVD) claims 1 person every 10 min in Australia and causes 1 in 3 deaths worldwide. The molecular and cellular processes underlying atherosclerosis, vascular injury and thrombosis are highly complex and not well understood. A multifaceted approach is needed to effectively address these key challenges. This Program brings together world experts in these areas to interrogate gaps in our basic understanding of CVD, and to develop novel therapies for CVD patients by exploiting new knowledge through integrated research.Read moreRead less
Investigating The Link Between Oxidative Stress And Biomechanical Integrin Activation In Diabetes
Funder
National Health and Medical Research Council
Funding Amount
$653,742.00
Summary
Diabetes represents a serious healthcare problem globally. A large proportion of deaths associated with diabetes can be attributed to the development of blood clots in the circulation of the heart and brain (heart attack/stroke). The blood clotting mechanism is ‘hyperactive’ in diabetes, although the reason for this is not well defined. In this proposal we will investigate a new mechanism promoting blood clots, and will investigate innovative approaches to reduce this clotting mechanism.
The Aboriginal Cardiovascular Omega-3 Randomised Controlled Trial
Funder
National Health and Medical Research Council
Funding Amount
$1,090,119.00
Summary
CVD is the primary contributor to life expectancy differentials between Indigenous and non-Indigenous Australians. Even when cardioprotective therapies are optimally used, residual risk of adverse events is often observed. Testing of additional therapies that improve survival among Indigenous people with CVD is required. Omega 3 fatty acids can improve multiple atherogenic pathways. This trial will assess the impact of Omega 3 in Aboriginal patients with CVD.
The Identification Of Thoracic Targets For Prevention And Intervention In Bronchopulmonary Dysplasia
Funder
National Health and Medical Research Council
Funding Amount
$316,449.00
Summary
The persistence of breathing problems from infancy to later life is a complication of premature birth with lifelong consequences. Breathing problems often occur together with lung disease, but prematurity can also affect heart and blood vessel development, and weakness of the main breathing muscle. We will find out how much the heart, lungs and diaphragm contribute to breathing problems in babies; helping us to better predict, diagnose and treat severe breathing problems in babies born preterm.
The Structural Basis For Glutamate Transporter Function
Funder
National Health and Medical Research Council
Funding Amount
$373,144.00
Summary
Glutamate transporters are vacuum cleaners in the brain that suck the neurotransmitter glutamate into cells. When the glutamate vacuum breaks down or becomes blocked, glutamate levels outside cells increase, leading to cell death in the brain. This process underlies the damage in many brain diseases including Alzheimer’s disease and stroke. The aim of this project is to understand the mechanism of the glutamate vacuum cleaner so we can develop therapeutics to fix it when it breaks down.
External Therapeutic Device To Support Rehabilitation Of The Hand Following Trauma Or Surgery
Funder
National Health and Medical Research Council
Funding Amount
$175,000.00
Summary
The loss of hand function will affect every aspect of an individual’s life. This includes the ability to feed and care for themselves and the ability to work and participate in family life. For people recovering from problems such as trauma, burns or surgery affecting the hand, careful management of hand rehabilitation can influence the outcome for the patient significantly. In order to reduce the possibility of mobility difficulties occurring, including loss of joint range of motion, muscle and ....The loss of hand function will affect every aspect of an individual’s life. This includes the ability to feed and care for themselves and the ability to work and participate in family life. For people recovering from problems such as trauma, burns or surgery affecting the hand, careful management of hand rehabilitation can influence the outcome for the patient significantly. In order to reduce the possibility of mobility difficulties occurring, including loss of joint range of motion, muscle and tendon sheath adhesions or non-functional scar tissue formation, continuous passive motion (CPM) is often indicated. Additionally, for people with reduced mobility of the hand due to upper limb paralysis, such as those with cervical spinal cord injury, stroke, cerebral palsy or peripheral nerve injury, disregard for management of the maintenance of the joint range of motion of the effected hand will result in contracture and limited joint range of motion. Such syndromes will reduce hand function, which is already limited by paralysis, and will negatively affect potential outcomes for aggressive rehabilitation techniques, such as tendon transfer surgery and functional neuromuscular stimulation. Therefore, in such cases, CPM is also indicated. Current devices applying CPM have shown to be effective in minimising the syndromes indicated above and these results are summarised in the Background and Research Plan attached to this proposal. Unfortunately, the use of such devices is not always prescribed by clinicians. This is due, mainly, to the limitations of these devices that are in the marketplace. These limitations include lack of secure finger placement, lack of portability, the inability to provide specialised therapy to specific joints and inflexible programming. This proposal introduces an improved device to be developed and these improvements form the proposal aims below. Given such an improved device, which can overcome many of the problems with current CPM machines, it is likely that that the clinical application of CPM will achieve the greater degree of prescription and application in hand rehabilitation. These improvements should overcome the clinical reticence to use these devices and restore a balance by increasing their use to the level that the scientific literature indicates they should have. The overall aim of the proposal is to take the device to a stage where it is ready for clinical trial.Read moreRead less