The Anti-thrombotic Potential Of Immunoreceptors In Platelet Thrombus Formation
Funder
National Health and Medical Research Council
Funding Amount
$522,773.00
Summary
Platelets are small cells in the blood stream that play an important role in preventing excessive blood loss at sites of tissue injury by sticking together and forming a haemostatic plug. Excessive platelet clumping in diseased blood vessels can lead to blockages and cause thrombotic diseases such as heart attack and stroke, two of the biggest killers of humans in the western world. In this proposal, we will seek to understand how immunoreceptors expressed on the surface of platelets modulate th ....Platelets are small cells in the blood stream that play an important role in preventing excessive blood loss at sites of tissue injury by sticking together and forming a haemostatic plug. Excessive platelet clumping in diseased blood vessels can lead to blockages and cause thrombotic diseases such as heart attack and stroke, two of the biggest killers of humans in the western world. In this proposal, we will seek to understand how immunoreceptors expressed on the surface of platelets modulate the function of platelet collagen interactions involving collagen GPVI receptor, the low affinity IgG receptor, FcgammaRIIa and the major platelet integrin, integrin alphaIIbbeta3. The aims of this work will define the role of these receptors in platelet aggregation both in cell-based assays and in mouse models of thrombosis. This work could lead to new strategies for therapeutic management of thrombotic disorders.Read moreRead less
A Newly Identified Role For 14-3-3zeta Protein In Thrombosis And Platelet Procoagulant Activity
Funder
National Health and Medical Research Council
Funding Amount
$556,327.00
Summary
Cardiovascular disease, including heart attack and stroke is the major cause of death globally, and is responsible for the death of 50,000 Australians each year. Platelet activation and blood coagulation play an important role in these diseases and we have discovered that a protein called 14-3-3 zeta is important in the processes that result in thrombosis. We are studying the mechanisms by which this protein contributes to life-threatening platelet activation with the aim of developing new and m ....Cardiovascular disease, including heart attack and stroke is the major cause of death globally, and is responsible for the death of 50,000 Australians each year. Platelet activation and blood coagulation play an important role in these diseases and we have discovered that a protein called 14-3-3 zeta is important in the processes that result in thrombosis. We are studying the mechanisms by which this protein contributes to life-threatening platelet activation with the aim of developing new and more effective anti-thrombotic drugs.Read moreRead less
Regulating Platelet Thrombus Formation By Inhibitory Co-receptors
Funder
National Health and Medical Research Council
Funding Amount
$441,000.00
Summary
Platelets are a specialised adhesive cell essential for normal blood clotting. Following induction of blood vessel injury, platelets stick to sites of injury and activation mediate platelet spreading, aggregation and stable blood clot formation. Platelet adhesion to components of the blood vessel in flowing blood is central to blood clot formation. We are studying the role of inhibitory receptors that regulate the platelet adhesion phase on the blood vessel surface. We have knockout mice that la ....Platelets are a specialised adhesive cell essential for normal blood clotting. Following induction of blood vessel injury, platelets stick to sites of injury and activation mediate platelet spreading, aggregation and stable blood clot formation. Platelet adhesion to components of the blood vessel in flowing blood is central to blood clot formation. We are studying the role of inhibitory receptors that regulate the platelet adhesion phase on the blood vessel surface. We have knockout mice that lack a specific protein, Platelet Endothelial Cell Adhesion Molecule-1 (PECAM-1) that we can use to study its functional role in blood clot models. We are developing transgenic mice to examine the important structural domains in PECAM-1 that lead to regulation of blood clots. The knowledge gained from this work will help to improve our understanding of the regulatory processes which influence the formation of a stable blood clot. This information is relevant to many human diseases including heart attack and stroke.Read moreRead less
Investigation Of A Novel Role For Factor XIII In Regulating The Adhesive Function Of Platelets
Funder
National Health and Medical Research Council
Funding Amount
$243,000.00
Summary
Platelets are small specialised blood cells that are extremely important for the normal formation of blood clots and for the repair of injured blood vessels. We are studying the processes that allow platelets to stick to the site of vessel injury and to each other to form stable blood clots. If this process proceeds unchecked, harmful blood clots can form which block blood vessels and cause heart attacks and strokes. There are many factors, both inside and outside platelets, which control how bi ....Platelets are small specialised blood cells that are extremely important for the normal formation of blood clots and for the repair of injured blood vessels. We are studying the processes that allow platelets to stick to the site of vessel injury and to each other to form stable blood clots. If this process proceeds unchecked, harmful blood clots can form which block blood vessels and cause heart attacks and strokes. There are many factors, both inside and outside platelets, which control how big and how fast a blood clot grows and whether it becomes harmful enough to cause a blood vessel blockage. One of these factors is the level of platelet 'stickiness' or 'reactivity'. We are working towards a better understanding of how platelet reactivity is regulated. Specifically, we believe we have identified a new factor which keeps blood clots at a size that is not harmful to cause blood vessel blockade. This information will not only increase our knowledge of blood clot formation in health and disease but also may help in the development of new therapies for the prevention of heart attack and stroke.Read moreRead less
Investigate Novel Functional Roles For PI 3-kinases In Platelets.
Funder
National Health and Medical Research Council
Funding Amount
$537,215.00
Summary
Platelets are small blood cells which have a well defined role in blood clotting. There is a growing body of evidence that platelets play an important role in a broad range of inflammatory diseases, and we have identified a key role for the platelet PI3K enzyme in controlling the pro-inflammatory function of platelets. This grant will examine the importance of PI3K in health and disease, and examine the potential therapeutic benefits of inhibiting platelet PI3K.
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.
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.
Identification Of A Novel Adhesion Mechanism Regulating Platelet-endothelial Interactions.
Funder
National Health and Medical Research Council
Funding Amount
$501,691.00
Summary
Platelets are important blood cells, stopping bleeding in the event of blood vessel injury. However, platelets can also interact with the blood vessel lining (endothelium) to regulate and in some cases promote inflammation. We have identified a new structure platelets use to stick to endothelium, which under disease states (enhanced oxidative stress), can promote inflammation. We will investigate how tractopods form, and examine their role in the setting of elevated oxidative stress and inflamma ....Platelets are important blood cells, stopping bleeding in the event of blood vessel injury. However, platelets can also interact with the blood vessel lining (endothelium) to regulate and in some cases promote inflammation. We have identified a new structure platelets use to stick to endothelium, which under disease states (enhanced oxidative stress), can promote inflammation. We will investigate how tractopods form, and examine their role in the setting of elevated oxidative stress and inflammatory disease.Read moreRead less
Investigate The Role Of PAF And CD40 Ligand In Regulating The Proinflammatory Properties Of Platelets
Funder
National Health and Medical Research Council
Funding Amount
$507,270.00
Summary
The cells of the blood play an important role in maintaining healthy blood vessels. We are interested in two types of blood cells, platelets and leukocytes, which together play a key role in vessel maintenance, by promoting blood clot formation and vessel wall repair following injury. However, while critical for normal blood vessel maintenance, these cells have also been demonstrated to contribute to disease states including atherosclerosis, thrombosis and inflammatory airway diseases. Underlyin ....The cells of the blood play an important role in maintaining healthy blood vessels. We are interested in two types of blood cells, platelets and leukocytes, which together play a key role in vessel maintenance, by promoting blood clot formation and vessel wall repair following injury. However, while critical for normal blood vessel maintenance, these cells have also been demonstrated to contribute to disease states including atherosclerosis, thrombosis and inflammatory airway diseases. Underlying the function of both blood cell types is their ability to stick (or adhere) to each other. However the way in which they coordinate this adhesion is very complex. New information from our laboratory has demonstrated that the sticky behaviour of each cell type is spatially and temporally regulated, and may involve may factors both inside and outside of the cells themselves. Our studies aim to define the key components regulating the 'stickiness' of these blood cells, in order to undertand how they contribute to maintaining healthy vessel walls, but also how their stickiness may also contribute to the promotion of diseased vessels. This information will not only increase our knowledge of the factors that regulate blood clot formation, but may also assist in the development of new therapies to prevent and-or treat vessel disease.Read moreRead less