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.
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.
Investigation Into The Intervention Of Arterial Thrombosis And Atherosclerosis Using Shear Sensitive Nanoparticle Drug Delivery
Funder
National Health and Medical Research Council
Funding Amount
$462,601.00
Summary
In this project we aim to provide a targeted therapy that inhibits atherosclerosis, in-stent restenosis and thrombosis; pathologies characterized by high shear stress due to a reduction in the vessel lumen. We will apply microfluidic technology to characterize lipid nano-capsules that are tagged with antibodies against activated platelets or VCAM-1, loaded with anti-platelet or immune suppressive drugs and are prone to rupture specifically under high shear stress conditions.
Blood clotting is the underlying cause of heart attacks and strokes. We have discovered that the protein, ERp5, is essential for normal blood clotting. Our preliminary findings indicate that ERp5 controls the function of blood platelets in clotting. Our overall aim is to elucidate how ERp5 regulates platelet function. It is crucial that we understand how ERp5 functions in blood clotting if we are to effectively target it in disease.
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
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.
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
Astrocytes, Mutant TDP-43 And Non-cell Autonomous Injury Of Motoneurons
Funder
National Health and Medical Research Council
Funding Amount
$626,492.00
Summary
Motor neuron disease (MND) leads to death of nerve cells, paralysis and death. There is no cure. Mutations in the protein TDP43 cause MND. In this study we will investigate the underlying mechanisms of which these mutations cause disease. We will also investigate how these mutations affect astrocytes, a cell type that maintains normal function and survival of nerve cells and determine if the mutations affect the important interactions that normally takes place between these cell types.
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.