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
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
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
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
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.
The Role Of The Platelet Glycoprotein Ib Alpha Cytoplasmic Domain In Thrombosis
Funder
National Health and Medical Research Council
Funding Amount
$600,230.00
Summary
Our studies aim to provide a better understanding of the factors that make platelets sticky, because this is important not only for normal blood clot formation but also in the development of harmful blood clots (thrombosis). Improving our understanding of these processes will add significantly to our knowledge of how blood clotting is controlled. This information is relevant to many human diseases including heart attack and stroke and will help us to develop drugs to prevent these diseases.