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
Investigate The Role For Dok Adapter Proteins In Thrombosis And Haemostasis.
Funder
National Health and Medical Research Council
Funding Amount
$161,737.00
Summary
Blood platelets play a key role in blood clot formation, prevention of bleeding and are the principal elements contributing to thrombosis leading to heart attack and stroke. Numerous studies have defined pathways promoting platelet activity, however less is known about their negative regulation. In this fellowship I will examine the role for proteins, Dok2 and Dok1, in the negative regulation of platelets, hoping this leads to development of novel therapeutics for prevention of cardiac disease.
Dissecting FLT3 Signalling In Acute Myeloid Leukaemia
Funder
National Health and Medical Research Council
Funding Amount
$498,328.00
Summary
Each year approximately 6000 Australian adults and children are diagnosed with leukaemia, lymphoma or a related blood disorder, accounting for about 15% of all cancers. Acute Myeloid Leukaemia (AML) is the most common form of leukaemia in adults resulting from an accumulation of immature myeloid cells in the bone marrow and peripheral blood as a result of sustained, abnormal cell growth and survival together with a block in normal blood cell formation. There is still a major research effort aime ....Each year approximately 6000 Australian adults and children are diagnosed with leukaemia, lymphoma or a related blood disorder, accounting for about 15% of all cancers. Acute Myeloid Leukaemia (AML) is the most common form of leukaemia in adults resulting from an accumulation of immature myeloid cells in the bone marrow and peripheral blood as a result of sustained, abnormal cell growth and survival together with a block in normal blood cell formation. There is still a major research effort aimed at understanding the mechanisms that lead to AML formation and it is clear that multiple AML oncogenes and tumour suppressors remain to be identified. Identification of further events involved in AML is important as it will provide avenues for more specific and less toxic treatments. These are needed because current success rates for AML remain relatively poor. It is critical that research into the understanding of the pathways and events involved in AML keeps pace with the rapid development of new approaches for therapeutic agents. Together this will greatly increase the scope for therapeutic intervention over the next decade. In this application we investigate the role of a new molecular pathway in AML. Our studies have identified a gene of particular interest that we propose normally prevents AML formation and therefore is frequently turned off by the cellular changes that lead to AML. We propose that silencing of this gene is particularly important in those AML cases which have mutations in the cell surface receptor FLT3 (about 30% of AML cases). We will use a number of molecular and cell biology approaches to manipulate this gene in mouse cell lines, normal mouse cells and human AML cells. A better understanding of the role of this gene and the associated pathway involving FLT3 may generate new leads for therapeutic approaches.Read moreRead less
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
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.