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.
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
Investigate Novel Functional Roles For PI 3-kinases In Platelets.
Funder
National Health and Medical Research Council
Funding Amount
$537,215.00
Summary
Platelets are small blood cells which have a well defined role in blood clotting. There is a growing body of evidence that platelets play an important role in a broad range of inflammatory diseases, and we have identified a key role for the platelet PI3K enzyme in controlling the pro-inflammatory function of platelets. This grant will examine the importance of PI3K in health and disease, and examine the potential therapeutic benefits of inhibiting platelet PI3K.
Investigation Of Mechanotransduction Mechanisms In Platelets
Funder
National Health and Medical Research Council
Funding Amount
$481,500.00
Summary
Platelets are extremely important cells that stop bleeding by sticking to injured blood vessel walls, forming blood clots. Excessive clotting can lead to fatal vascular events such as heart attack and stroke. On the other hand, defects in blood clotting can result in life threatening bleeding problems. Platelets stick to sites of vessel wall injury through the interaction between cell surface receptors and sticky materials (proteins) that become exposed to the blood flow when the vessel wall is ....Platelets are extremely important cells that stop bleeding by sticking to injured blood vessel walls, forming blood clots. Excessive clotting can lead to fatal vascular events such as heart attack and stroke. On the other hand, defects in blood clotting can result in life threatening bleeding problems. Platelets stick to sites of vessel wall injury through the interaction between cell surface receptors and sticky materials (proteins) that become exposed to the blood flow when the vessel wall is damaged. The stickiness of platelets is controlled by many proteins (and-or enzymes) inside these blood cells. These proteins transmit messages from platelet receptors on the surface into the cell interior, thereby controlling platelet behaviour. We are in the process of identifying several types of proteins-enzymes which are responsible for controlling platelet stickiness. The studies proposed in this application will provide better understanding of the complicated pathways regulating platelet stickiness and clot formation. The knowledge gained may utimately assist in the design of specific drugs for the prevention and-or treatment of heart attacks and strokes.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.
Investigation Of A New Rheology Dependent Platelet Aggregation Mechanism
Funder
National Health and Medical Research Council
Funding Amount
$509,447.00
Summary
We plan to examine a new mechanism promoting blood clot formation that involves the clumping (aggregation) of blood platelets. Our central hypothesis is that disturbances of blood flow, as occurs in diseased arteries, activates this clotting mechanism through a unique platelet activation process. Defining this new activation mechanism has the potential to lead to new approaches to prevent blood clot formation in patients with heart disease.
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.