The mechanisms regulating expression and function of surface receptors on blood platelets are critical for understanding cardiovascular diseases involving aberrant platelet function, not only thrombotic diseases such as heart attack or stroke, but other pathology involving platelets including coagulopathy and autoimmune thrombocytopenia caused by anti-platelet antibodies. Improved diagnosis and therapeutic targeting of platelet-specific receptors mediating arterial thrombosis can save many lives ....The mechanisms regulating expression and function of surface receptors on blood platelets are critical for understanding cardiovascular diseases involving aberrant platelet function, not only thrombotic diseases such as heart attack or stroke, but other pathology involving platelets including coagulopathy and autoimmune thrombocytopenia caused by anti-platelet antibodies. Improved diagnosis and therapeutic targeting of platelet-specific receptors mediating arterial thrombosis can save many lives given the prevalence and severity of disease.Read moreRead less
Investigating The Contribution Of Distinct Mitochondrial Cell Death Pathways To Platelet Survival And Function
Funder
National Health and Medical Research Council
Funding Amount
$635,247.00
Summary
Platelets are small blood cells that form clots to stop bleeding. We have found new and unexpected roles for 2 distinct pathways that regulate cell death in the process of blood clot formation. We will study the precise role of these pathways in blood clot formation, and determine whether they may also regulate the survival of platelets stored by the blood bank for transfusion. These studies will provide new insight into the role of cell death pathways in blood clot formation, and may help to im ....Platelets are small blood cells that form clots to stop bleeding. We have found new and unexpected roles for 2 distinct pathways that regulate cell death in the process of blood clot formation. We will study the precise role of these pathways in blood clot formation, and determine whether they may also regulate the survival of platelets stored by the blood bank for transfusion. These studies will provide new insight into the role of cell death pathways in blood clot formation, and may help to improve current protocols for storing plateletsRead moreRead less
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.
Investigation Of The Role For GPVI In Platelet Function And Thrombosis
Funder
National Health and Medical Research Council
Funding Amount
$542,772.00
Summary
Blood cells play an important role in maintaining healthy blood vessels. We are studying the role of platelets in blood clots following vessel injury. However, while critical for normal blood vessel maintenance, these cells also contribute to diseases including thrombosis. We will examine how an important platelet receptor called GPVI promotes blood clot formation, and examine whether combining anticoagulant drugs with GPVI deficient platelets leads to a more effective anticlotting approach.
Investigating A Potential New Treatment For Stroke
Funder
National Health and Medical Research Council
Funding Amount
$878,522.00
Summary
Blood clots blocking blood flow to the brain (stroke) are a major cause of death and disability. Safety concerns limit approved therapies to a small subset of patients, highlighting an urgent need for safer, more effective drugs. Our studies show that inhibitors of the enzyme PI3Kbeta increase blood clot permeability, increasing clot ‘dissolvability’, without increased bleeding. This raises the possibility that PI3Kbeta inhibitors may represent a safe and effective adjuvant therapy for stroke.
Investigating A Novel Role For The Haemopoietic Growth Factor Receptor, C-Mpl, In Regulating Shear-dependent Platelet Adhesive Function
Funder
National Health and Medical Research Council
Funding Amount
$570,294.00
Summary
Platelets play a critical role in blood clot formation, with low platelet numbers leading to bleeding while excessive clot formation can cause heart attack and stroke. Platelets must ‘stick’ to injured blood vessels under blood flow (shear). We have discovered that the growth factor, c-Mpl, can regulate shear-dependent platelet sticking by controlling receptor ‘shedding’ from the cell surface. We will investigate how c-Mpl performs this new role, and examine platelet function in patients with my ....Platelets play a critical role in blood clot formation, with low platelet numbers leading to bleeding while excessive clot formation can cause heart attack and stroke. Platelets must ‘stick’ to injured blood vessels under blood flow (shear). We have discovered that the growth factor, c-Mpl, can regulate shear-dependent platelet sticking by controlling receptor ‘shedding’ from the cell surface. We will investigate how c-Mpl performs this new role, and examine platelet function in patients with myeloproliferative disease who have reduced c-Mpl.Read moreRead less
Seminal findings within our laboratory have demonstrated that disturbances of blood flow are an important trigger for blood clot formation, promoting heart attacks and stroke. Our studies have demonstrated that specialised blood cells, termed platelets, respond rapidly to local changes in blood flow in diseased blood vessels. In the present proposal we aim to identify the mechanisms by which platelets sense and respond to blood flow disturbances with the aim of identifying new approaches to prev ....Seminal findings within our laboratory have demonstrated that disturbances of blood flow are an important trigger for blood clot formation, promoting heart attacks and stroke. Our studies have demonstrated that specialised blood cells, termed platelets, respond rapidly to local changes in blood flow in diseased blood vessels. In the present proposal we aim to identify the mechanisms by which platelets sense and respond to blood flow disturbances with the aim of identifying new approaches to prevent disease-causing blood clots.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