Identification Of A New Thrombosis Mechanism Triggered By Dying Platelets
Funder
National Health and Medical Research Council
Funding Amount
$608,742.00
Summary
A severe reduction in blood flow (ischemia) to the intestines can trigger blood clot formation (thrombosis) in multiple organs, including the lungs. We have identified a new thrombosis mechanism that is triggered by the clumping of white blood cells in the intestines, leading to widespread thrombosis in the lung. Here we will investigate the mechanisms triggering this thrombosis mechanism with the ultimate aim of identifying more effective antithrombotic approaches.
Intravascular Leukocyte Trafficking During Thromboinflammation
Funder
National Health and Medical Research Council
Funding Amount
$668,742.00
Summary
Unblocking blood vessels to treat heart attack and stroke can unfortunately cause a paradoxical worsening of organ damage, due to increased inflammation upon blood flow restoration. We have identified a novel way in which this side-effect is regulated by the small blood clotting cells platelets, and the protein fibrin. We will investigate ways to reduce the pro-inflammatory role for platelets, and define safer clot busting treatments.
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.
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.
Heparin-induced Thrombocytopenia And Thrombosis: Better Understanding Of Pathogenesis And Improving Diagnosis And Treatment
Funder
National Health and Medical Research Council
Funding Amount
$653,137.00
Summary
Heparin, a widely used drug, can cause an adverse effect which results in a fall of the platelet count and the development of serious thrombosis. This drug complication is mediated by an immune mechanism. This proposal aims to provide a better understanding of the disease mechanism. It also aims to develop a new test that will improve the diagnosis, and to produce a novel drug that will effectively suppress the immune reaction and improve the treatment.
Targeting A Novel Anti-platelet Mechanism For Improved Anti-thrombotic Therapy
Funder
National Health and Medical Research Council
Funding Amount
$985,938.00
Summary
Blood clots cause heart attacks and most strokes, which are the most common cause of death in the world. Platelets are the cells in the blood that form these clots, and drugs that prevent platelet function are the major approach for heart attack and stroke prevention. However, many patients are resistant to the effects of existing therapies. These studies will develop a unique approach to prevent platelet function that may help overcome the limitations of current drugs.
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
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