Investigate The Role Of Platelet Von Willebrand Factor In Initiating Platelet Aggregation Under Flow
Funder
National Health and Medical Research Council
Funding Amount
$307,165.00
Summary
Platelets are small specialised blood cells that are essential for normal blood clotting and repair of damaged blood vessels following injury. We are studying the processes that enable platelets to stick to each other and to other cells to form a stable blood clot at the site of injury. The same processes, unchecked, are involved in the formation of harmful blood clots in the bloodstream that may block blood vessels in the heart or brain and result in a heart attack or stroke. Platelets stick to ....Platelets are small specialised blood cells that are essential for normal blood clotting and repair of damaged blood vessels following injury. We are studying the processes that enable platelets to stick to each other and to other cells to form a stable blood clot at the site of injury. The same processes, unchecked, are involved in the formation of harmful blood clots in the bloodstream that may block blood vessels in the heart or brain and result in a heart attack or stroke. Platelets stick to the blood vessel wall through specialised adhesive proteins. These adhesion proteins are stored within the platelet and expressed on the cell surface when the platelets stick to the blood vessel wall. In conditions such as Gray Platelet Syndrome, the platelets are unable to store adhesion receptors, resulting in impaired blood clot formation. A clearer understanding of how platelets stick to the blood vessel wall will not only increase our knowledge of blood clot formation in health and disease, but also with the potential development of new therapies for the prevention of heart disease and stroke.Read moreRead less
Muscarinic Receptor Signalling, Transglutaminase And Diabetes
Funder
National Health and Medical Research Council
Funding Amount
$518,210.00
Summary
Diabetes is a major and increasing cuase of death and disability in our society. This studies aims to understand the cellular and molecular mechaisms controlling insulin secretion from the pancreas, since defects in this secretion are involved in causing diabetes. The proposed studies are of relevance to both juvenile and adult-onset diabetes, and may lead to new treatment modalities, as well as potentially being relevant to the use of pencreatic islet cell transplantation in the treatment of di ....Diabetes is a major and increasing cuase of death and disability in our society. This studies aims to understand the cellular and molecular mechaisms controlling insulin secretion from the pancreas, since defects in this secretion are involved in causing diabetes. The proposed studies are of relevance to both juvenile and adult-onset diabetes, and may lead to new treatment modalities, as well as potentially being relevant to the use of pencreatic islet cell transplantation in the treatment of diabetes.Read moreRead less
Novel Selective Anti-platelet And Clot-specific Anticoagulant Strategies Targeting Conformational States Of GPIIb/IIIa
Funder
National Health and Medical Research Council
Funding Amount
$496,517.00
Summary
The inhibition of platelets and the inhibition of coagulation factors are among the most widely used drugs in medicine and provide major benefits for numerous patients. Prevention and treatment of thrombosis, emboli, stroke and heart attack are examples of the many diseases where anti-platelet and anticoagulant drugs are administered. However, the downsides of these drugs are bleeding complications, which can result in death or disability. The consequences of these drug-associated bleeding compl ....The inhibition of platelets and the inhibition of coagulation factors are among the most widely used drugs in medicine and provide major benefits for numerous patients. Prevention and treatment of thrombosis, emboli, stroke and heart attack are examples of the many diseases where anti-platelet and anticoagulant drugs are administered. However, the downsides of these drugs are bleeding complications, which can result in death or disability. The consequences of these drug-associated bleeding complications are also a major financal burden for our health care system. Thus, progress towards therapeutic strategies with less bleeding complications is highly sought-after. The proposed project aims to generate new antibody-based agents for platelet inhibition. One group of these agents do only block platelets when they are activated. Furthermore, these agents allow an enrichment of potent inhibitors of coagulation factors at the site of the clot. Thus, these inhibitors should predominatly act at the site where they are needed. At the same time the overall concentration of inhibitors of coagulation factors can be kept low and the functions of non-activated platelet can be left intact. Overall, the proposed project aims for the development of novel anti-platelet and anticoagulant strategies with high anti-thrombotic efficacy and low bleeding risks.Read moreRead less
Integrin-growth Factor Interactions In The Development Of Airway Wall Remodelling
Funder
National Health and Medical Research Council
Funding Amount
$405,300.00
Summary
Asthma is a clinically and socio-economically important disease with prevalence in the Australian population of approximately 13% for adults and approaching 25% for children. Currently, glucocorticoids (GCS) are first line prophylactic therapy for the disease. Despite a wide diversity of precipitating factors, the mechanisms underlying its pathogenesis remain unclear. A marked thickening of the airway wall bought about by excessive deposition of extracellular matrix is a prominent pathological f ....Asthma is a clinically and socio-economically important disease with prevalence in the Australian population of approximately 13% for adults and approaching 25% for children. Currently, glucocorticoids (GCS) are first line prophylactic therapy for the disease. Despite a wide diversity of precipitating factors, the mechanisms underlying its pathogenesis remain unclear. A marked thickening of the airway wall bought about by excessive deposition of extracellular matrix is a prominent pathological feature but why this occurs and how it can be prevented is equally unclear. Recent studies have suggested that interactions between cells and the extracellular matrix influence the airways response to inflammation and modulate the effectiveness of currently available therapies. Indeed, there is mounting evidence to suggest that GCS fail to modulate and indeed in some cases even contribute to structural changes in the remodeled airway wall. The aim of this study is to assess the mechanisms by which cells and the extracellular matrix interact to promote remodelling of the airway wall and to determine whether this association influences the responsiveness to traditional asthma therapies.Read moreRead less