Proof-of-concept Studies For A Novel Anti-thrombotic Agent
Funder
National Health and Medical Research Council
Funding Amount
$632,352.00
Summary
Blood clots cause most heart attacks and strokes, and platelets are the blood cells that form these clots. Drugs that block platelet function, such as aspirin, are used to prevent heart attack and stroke but are frequently ineffective. Here, we will develop a new drug that prevents platelet incorporation into blood clots, that will be suitable for the prevention of heart attack and stroke in humans, and that may improve on existing therapies.
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.
Mechanisms Underlying The Effects Of Retinoic Acid Receptor Gamma In Haemopoiesis And Bone Homeostasis
Funder
National Health and Medical Research Council
Funding Amount
$366,801.00
Summary
My recent studies have demonstrated that a model of vitamin A deficiency results in impaired blood cell production and contributes to a blood cell disorder that can progress to leukaemia. There are also reduced numbers of blood stem cells (which give rise to all blood cells) and bone (which helps to regulate blood cell production) in this mouse model. In these studies I seek to understand more on how vitamin A deficiency causes these defects, which may lead to better treatment of such diseases.
Regulating Platelet Thrombus Formation By Inhibitory Co-receptors
Funder
National Health and Medical Research Council
Funding Amount
$441,000.00
Summary
Platelets are a specialised adhesive cell essential for normal blood clotting. Following induction of blood vessel injury, platelets stick to sites of injury and activation mediate platelet spreading, aggregation and stable blood clot formation. Platelet adhesion to components of the blood vessel in flowing blood is central to blood clot formation. We are studying the role of inhibitory receptors that regulate the platelet adhesion phase on the blood vessel surface. We have knockout mice that la ....Platelets are a specialised adhesive cell essential for normal blood clotting. Following induction of blood vessel injury, platelets stick to sites of injury and activation mediate platelet spreading, aggregation and stable blood clot formation. Platelet adhesion to components of the blood vessel in flowing blood is central to blood clot formation. We are studying the role of inhibitory receptors that regulate the platelet adhesion phase on the blood vessel surface. We have knockout mice that lack a specific protein, Platelet Endothelial Cell Adhesion Molecule-1 (PECAM-1) that we can use to study its functional role in blood clot models. We are developing transgenic mice to examine the important structural domains in PECAM-1 that lead to regulation of blood clots. The knowledge gained from this work will help to improve our understanding of the regulatory processes which influence the formation of a stable blood clot. This information is relevant to many human diseases including heart attack and stroke.Read moreRead less
Cytoskeletal Regulation Of Platelet Adhesion And Thrombus Formation
Funder
National Health and Medical Research Council
Funding Amount
$406,527.00
Summary
Platelets are small specialised blood cells that are essential for normal blood clotting and repair of damaged blood vessels following injury. When platelets stick to sites of blood vessel injury they undergo dramatic changes in their shape and internal structure that are necessary for these cells to spread over the damaged surface and facilitate the formation of a stable blood clot. We are studying these changes in the intracellular structure (cytoskeleton) of platelets and how these events mig ....Platelets are small specialised blood cells that are essential for normal blood clotting and repair of damaged blood vessels following injury. When platelets stick to sites of blood vessel injury they undergo dramatic changes in their shape and internal structure that are necessary for these cells to spread over the damaged surface and facilitate the formation of a stable blood clot. We are studying these changes in the intracellular structure (cytoskeleton) of platelets and how these events might regulate the reactivity of platelets and their ability to adhere to blood vessels. An understanding of these processes will add significantly to our knowledge of how blood clots. This information is relevant to many human diseases such as heart attack and stroke.Read moreRead less