New Insights Into The Mechanisms Of Thrombogenesis In Atrial Fibrillation
Funder
National Health and Medical Research Council
Funding Amount
$443,946.00
Summary
Atrial fibrillation (AF) is the most common heart rhythm disturbance (arrhythmia), which is associated with a high risk of stroke due to clot formation within the left atria. At present we still only have a limited understanding of the mechanism of clot formation in AF. The aim of this study is to determine the critical mechanisms that contribute to clot formation within the left atria in AF. This knowledge is fundamental to the development of more successful interventional approaches.
An Investigation Of The Involvement Of Clotting Factors In Abdominal Aortic Aneurysm (AAA) Progression Within A Mouse Model
Funder
National Health and Medical Research Council
Funding Amount
$189,401.00
Summary
Early stage weakening of the main abdominal artery is present in ~100,000 Australians and currently has no accepted therapy. Development of drug therapies which limit progression of the weakening process is urgently needed. In this study involvement of the clotting cascade in artery weakening will be investigated. The study have been planned in order to identify new strategies which can be developed as treatments for artery weakening in patients.
Molecular Imaging And Therapy Of Cardiac Fibrosis In Atrial Fibrillation And Heart Failure
Funder
National Health and Medical Research Council
Funding Amount
$1,021,656.00
Summary
Cardiac fibrosis is a serious medical condition which can lead to an irregular heart beat and heart failure. We will develop novel diagnostic agents which are more sensitive and able to detect fibrosis of the heart at an earlier time point. This would allow timely initiation of therapy. In addition, we will investigate novel targeted anti-fibrotic agents to treat this devastating disease condition more effectively and with less adverse effects.
Preventing Stroke From Arteriovenous Malformations Using Precision Thrombosis
Funder
National Health and Medical Research Council
Funding Amount
$993,866.00
Summary
Brain arteriovenous malformations are rupture-prone blood vessels that cause stroke in children and young adults. One third of patients have no current treatment options. We aim to develop new medicines that cause blockage of the abnormal vessels, thus preventing them from bleeding and causing stroke. Focused radiation is used to produce molecular changes in the abnormal vessels; these molecules are then the target for the new medicines. We will develop several new drugs for clinical testing.
Understanding How Tetraspanin Superfamily Members Modulate Platelet Function
Funder
National Health and Medical Research Council
Funding Amount
$469,500.00
Summary
Platelets are small cells in the blood stream that play an important role in preventing excessive blood loss at sites of tissue injury by sticking together and forming a haemostatic plug. Excessive platelet clumping in diseased blood vessels can lead to blockages and cause thrombotic diseases such as heart attack and stroke, two of the biggest killers of humans in the western world. In this proposal, we will seek to understand how tetraspanin superfamily members expressed on the surface of plate ....Platelets are small cells in the blood stream that play an important role in preventing excessive blood loss at sites of tissue injury by sticking together and forming a haemostatic plug. Excessive platelet clumping in diseased blood vessels can lead to blockages and cause thrombotic diseases such as heart attack and stroke, two of the biggest killers of humans in the western world. In this proposal, we will seek to understand how tetraspanin superfamily members expressed on the surface of platelets modulate the function of the major platelet integrin, integrin alphaIIbbeta3 and the low-affinity IgG receptor, FcgammaRIIa. This aims of this work will define the roles of these receptors in platelet clumping both in cell-based assays and in mouse models of thrombosis. This work could lead to new strategies for therapeutic management of thrombotic disorders.Read moreRead less
Investigation Of A New Platelet Contractile Mechanism Regulating Thrombus Stability
Funder
National Health and Medical Research Council
Funding Amount
$499,670.00
Summary
Platelets are small blood cells that form clots to stop bleeding. We have found a new contraction process that causes tight packing of platelets in a clot, enabling the clot to avoid detachment under blood flow. We will study this process and explore the possibility that its inhibition may provide a new way in which to loosen clots, promoting their removal. These studies will provide new insight into clot stability, and may provide clinical benefit in the delivery of clot dissolving agents .
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