Investigate The Role Of Ectoenzymes In Regulating The Haemostatic Function Of Human Platelets
Funder
National Health and Medical Research Council
Funding Amount
$215,882.00
Summary
Platelets are cells found in the blood that are essential for stopping bleeding after injury. These cells stick to the blood vessel wall and initiate the formation of a blood clot which plugs the injured blood vessel. Similiar processes are involved in the formation of harmful blood clots that block blood vessels in the heart or brain, causing heart attacks and stroks, respectively. Platelets stick to the blood vessel wall through proteins called receptors, which are located on the platelet surf ....Platelets are cells found in the blood that are essential for stopping bleeding after injury. These cells stick to the blood vessel wall and initiate the formation of a blood clot which plugs the injured blood vessel. Similiar processes are involved in the formation of harmful blood clots that block blood vessels in the heart or brain, causing heart attacks and stroks, respectively. Platelets stick to the blood vessel wall through proteins called receptors, which are located on the platelet surface. We are investigating the processes that naturally regulate these receptors and therefore modulate the adhesive properties of platelets. We have found that a group of enzymes, also located on the platelet surface, remove these receptors, thereby limiting the ability of these cells to stick to blood vessels and form clots. Unravelling these processes will not only help with our understanding of clot formation in health and disease, but also with the potential development of new therapies for the prevention of heart disease and stroke.Read moreRead less
Investigate The Role Of Platelet Von Willebrand Factor In Initiating Platelet Aggregation Under Flow
Funder
National Health and Medical Research Council
Funding Amount
$307,165.00
Summary
Platelets are small specialised blood cells that are essential for normal blood clotting and repair of damaged blood vessels following injury. We are studying the processes that enable platelets to stick to each other and to other cells to form a stable blood clot at the site of injury. The same processes, unchecked, are involved in the formation of harmful blood clots in the bloodstream that may block blood vessels in the heart or brain and result in a heart attack or stroke. Platelets stick to ....Platelets are small specialised blood cells that are essential for normal blood clotting and repair of damaged blood vessels following injury. We are studying the processes that enable platelets to stick to each other and to other cells to form a stable blood clot at the site of injury. The same processes, unchecked, are involved in the formation of harmful blood clots in the bloodstream that may block blood vessels in the heart or brain and result in a heart attack or stroke. Platelets stick to the blood vessel wall through specialised adhesive proteins. These adhesion proteins are stored within the platelet and expressed on the cell surface when the platelets stick to the blood vessel wall. In conditions such as Gray Platelet Syndrome, the platelets are unable to store adhesion receptors, resulting in impaired blood clot formation. A clearer understanding of how platelets stick to the blood vessel wall will not only increase our knowledge of blood clot formation in health and disease, but also with the potential development of new therapies for the prevention of heart disease and stroke.Read moreRead less
Investigation Of Shear-sensitive Signalling Pathways In Human Platelets
Funder
National Health and Medical Research Council
Funding Amount
$196,527.00
Summary
Platelets are extremely important cells that control bleeding by sticking to injured blood vessels to form a blood clot. Excessive clotting can lead to fatal vascular events such as heart attacks and strokes. On the other hand, defects in blood clotting can result in life threatening bleeding problems. Platelets stick to the wall of a blood vessel when receptors on the surface of these cells interact with materials (ligands) that are exposed when the vessel wall is injured. The stickiness or adh ....Platelets are extremely important cells that control bleeding by sticking to injured blood vessels to form a blood clot. Excessive clotting can lead to fatal vascular events such as heart attacks and strokes. On the other hand, defects in blood clotting can result in life threatening bleeding problems. Platelets stick to the wall of a blood vessel when receptors on the surface of these cells interact with materials (ligands) that are exposed when the vessel wall is injured. The stickiness or adhesive behaviour of platelets is controlled by many proteins (enzymes) which are contained inside these cells. These enzymes transmit messages from platelet receptors on the surface into the cell interior, thereby controlling platelet behaviour. We are in the process of identifying several types of enzymes which are responsible for controlling platelet stickiness. Our research will provide a better understanding of the complicated pathways regulating platelet stickiness and clot formation. The knowledge gained from these studies may ultimately asssist in the design of specific drugs for the prevention and-or treatment of heart attacks and strokes.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.
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