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 Novel Mechanisms Regulating Platelet Reactivity During Haemostasis And Thrombosis
Funder
National Health and Medical Research Council
Funding Amount
$221,210.00
Summary
Platelets are small specialised blood cells that are critical for normal blood clotting and blood vessel repair following injury. We are studying the processes that enable platelets to stick to the site of vessel injury and to each other to form a stable blood clot. These very processes, when unchecked, are responsible for 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. Many factors control how big ....Platelets are small specialised blood cells that are critical for normal blood clotting and blood vessel repair following injury. We are studying the processes that enable platelets to stick to the site of vessel injury and to each other to form a stable blood clot. These very processes, when unchecked, are responsible for 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. Many factors control how big and how rapidly a blood clot grows and whether it becomes harmful enough to lead to a heart attack or stroke. One of these factors is the level of platelet 'reactivity' or 'stickiness' . We are working towards a better understanding of how platelet reactivity is regulated and how this dictates the potential of a blood clot to become harmful. This knowledge will not only increase our knowledge of blood clot formation in health and disease, but also help in the development of new therapies for the prevention of heart attack 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 Negative Signalling Mechanisms In Platelets
Funder
National Health and Medical Research Council
Funding Amount
$292,500.00
Summary
Platelets are specialised blood cells essential for normal blood clotting. We are studying the processes that control platelets sticking to the exposed vessel wall, to each other and to other cells to form a stable blood clot at the site of injury to stop bleeding. The same processes, when unchecked, could lead to the formation of harmful large blood clots that may block blood vessels in the heart or brain, resulting in heart attack or stroke. Platelets stick to the blood vessel wall and each ot ....Platelets are specialised blood cells essential for normal blood clotting. We are studying the processes that control platelets sticking to the exposed vessel wall, to each other and to other cells to form a stable blood clot at the site of injury to stop bleeding. The same processes, when unchecked, could lead to the formation of harmful large blood clots that may block blood vessels in the heart or brain, resulting in heart attack or stroke. Platelets stick to the blood vessel wall and each other through sticky proteins called receptors on the cell surface. Receptors are able to bind to their specific ligands such as von Willebrand factor (vWf) and collagen which become exposed following vessel wall damage. The interaction between the ligands and receptors will trigger many biochemical changes within platelets, called signal transduction, that control platelet stickiness. The aim of this research project is to investigate the signalling processes that are utilised by the major platelet receptor called integrin alpha IIb beta 3. We are particularly interested in identifying the negative signalling process utilised by this receptor to dampen the positive signals required for platelet stickiness, to achieve a balanced clotting process. The identification of these specific signalling pathways will not only increase our knowledge of blood clot formation in health and disease, but also help develop potential new therapies for the prevention of heart diseases and strokes.Read moreRead less
Molecular Pathways Mediating Quiescence And Resistance In Leukaemia Stem Cells In Acute Myeloid Leukaemia.
Funder
National Health and Medical Research Council
Funding Amount
$100,381.00
Summary
Acute myeloid leukaemia (AML) is a devastating cancer of the blood and bone marrow which is rapidly fatal unless effectively treated with chemotherapy. AML is caused by genetic events that alter normal blood stem cells to give them a growth and survival advantage and also may confer resistance to chemotherapy in some cases. We will evaluate and target the mechanism of this resistance in laboratory models. This information can then be used to design new treatments to improve outcomes in AML.