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
Platelet And Endothelial Function In Atrial Fibrillation
Funder
National Health and Medical Research Council
Funding Amount
$105,825.00
Summary
Atrial fibrillation is the most common heart rhythm disturbance in the adult population and leads to substantial increased death and disability from stroke. In this research scheme, we will study the contribution of platelet (clot forming cells) and endothelial (lining of blood vessels) dysfunction in atrial fibrillation. The successful outcome of this project will lead to a better understanding of the underlying mechanisms of clot formation and may lead to a better target for future drugs.
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
Investigation Of The Role Of Type II PI 3-kinases In Platelet Function
Funder
National Health and Medical Research Council
Funding Amount
$444,973.00
Summary
Inappropriate blood clot formation is the cause of most heart attacks and strokes, and platelets are the blood cells which form these clots. Current therapies that interfere with platelet function are used to prevent heart attack and stroke but are frequently ineffective. We will study the signals which control platelet incorporation into clots in order to discover improved therapeutic strategies for heart attack and stroke prevention.
Microfluidic Device Fo The Quantitative Assessment Of Blood Platelet Aggregation Behaviour
Funder
National Health and Medical Research Council
Funding Amount
$270,114.00
Summary
This project will develop a low-cost microfluidic chip which utilises dynamic shear stress to assess the propensity of blood clotting. This tool will analyze a tiny sample of blood and will predict excessive or ineffective clotting. The project will develop the chip and a low-cost 'chip reader' such that the tool can be operated at the point of care with only basic training.