Regulation Of Receptors That Control Platelet Function Under Shear Stress
Funder
National Health and Medical Research Council
Funding Amount
$507,273.00
Summary
Specialized human blood cells that control blood loss and clotting (platelets) are currently difficult to test in the clinical laboratory, meaning patients are at risk of excessive bleeding or serious clot formation during disease or treatment. The aim of this proposal is to use our new reagents and assays to develop more reliable methods for evaluating relative bleeding or clotting risk in individuals.
Identification Of A Novel Adhesion Mechanism Regulating Platelet-endothelial Interactions.
Funder
National Health and Medical Research Council
Funding Amount
$501,691.00
Summary
Platelets are important blood cells, stopping bleeding in the event of blood vessel injury. However, platelets can also interact with the blood vessel lining (endothelium) to regulate and in some cases promote inflammation. We have identified a new structure platelets use to stick to endothelium, which under disease states (enhanced oxidative stress), can promote inflammation. We will investigate how tractopods form, and examine their role in the setting of elevated oxidative stress and inflamma ....Platelets are important blood cells, stopping bleeding in the event of blood vessel injury. However, platelets can also interact with the blood vessel lining (endothelium) to regulate and in some cases promote inflammation. We have identified a new structure platelets use to stick to endothelium, which under disease states (enhanced oxidative stress), can promote inflammation. We will investigate how tractopods form, and examine their role in the setting of elevated oxidative stress and inflammatory disease.Read 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 Proinflammatory Function Of Platelets During Ischaemia-reperfusion Injury
Funder
National Health and Medical Research Council
Funding Amount
$552,720.00
Summary
Platelets are important blood cells that stop bleeding. Platelets also regulate inflammation by modulating the function of white blood cells. Excessive stimulation of white cells by platelets may cause tissue damage relevant to a broad of cardiovascular diseases, including heart disease and stroke. This grant application aims to investigate the precise mechanism by which platelets promote inflammation during a heart attack or stroke.
Investigation Of A Novel Mechanism Causing Platelet Hyperactivity In Diabetes
Funder
National Health and Medical Research Council
Funding Amount
$583,015.00
Summary
Diabetes represents a serious global health crisis, set to explode over the next few decades. A large proportion of deaths associated with Diabetes can be attributed to a high incidence of cardiovascular disease, with diabetic platelets shown to be ‘hyperactive’. We have defined a novel pathway sensitive to the shear forces of blood flow, which leads to platelet hyperactivity in diabetics. We will investigate potential ways to dampen this pathway, which may offer promise as novel treatments for ....Diabetes represents a serious global health crisis, set to explode over the next few decades. A large proportion of deaths associated with Diabetes can be attributed to a high incidence of cardiovascular disease, with diabetic platelets shown to be ‘hyperactive’. We have defined a novel pathway sensitive to the shear forces of blood flow, which leads to platelet hyperactivity in diabetics. We will investigate potential ways to dampen this pathway, which may offer promise as novel treatments for diabetic patients.Read moreRead less
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
Therapeutic Approaches To Circumvent NO• Resistance In The Type 2 Diabetic Heart And Vasculature
Funder
National Health and Medical Research Council
Funding Amount
$563,337.00
Summary
Type 2 diabetes (T2D) is Australia’s fastest growing chronic disease, affecting almost 2 million Australians (who face poor cardiovascular health outcomes). We have discovered an exciting new avenue that may potentially more effectively counteract heart and blood vessel disorders in T2D patients in an acute cardiovascular emergency, of substantial clinical importance.
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
Inhibition Of Haemostasis As A Novel Host-directed Therapy For Tuberculosis
Funder
National Health and Medical Research Council
Funding Amount
$528,471.00
Summary
Mycobacterium tuberculosis-induced vasculopathy is an important cause of stroke worldwide, and stroke is a common (~20%) complication of tuberculous meningitis, the most dangerous presentation of tuberculosis. Blood clotting may also speed the growth tuberculosis in the body further worsening the situation. We will use zebrafish find out if clotting can be targeted to slow the growth of mycobacteria and then translate our findings to a mouse model of pulmonary tuberculosis.
The Role Of Duffy And PF4 In The Platelet Killing Of Malaria Parasites.
Funder
National Health and Medical Research Council
Funding Amount
$350,045.00
Summary
Platelets in the blood can kill the Plasmodium parasite, which lives inside red blood cells and causes malaria. Platelets bind parasite-infected red cells and release a molecule that is toxic to the parasite. This project will study why a red cell molecule called Duffy is also needed for this function of platelets. Most Africans carry a gene for Duffy that stops its expression in red cells, and may therefore be more susceptible to malaria because their platelets cannot kill the malaria parasite.