Platelet Receptor Regulation In Autoimmune Disease
Funder
National Health and Medical Research Council
Funding Amount
$507,536.00
Summary
In response to bleeding, blood platelets use receptors to form a thrombus (blood clot) and block further loss of blood and aid tissue repair. People treated with heparin prior to surgery, can form autoantibodies that attack platelets, leading to thombus and thrombocytopenia (dangerous loss of circulating platelets). This is a significant clinical problem that is difficult to diagnose. We will determine how platelet receptor shedding can aid the diagnosis of heparin-induced thrombocytopenia.
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.
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 Dok2 And Dok1 Adapter Proteins, In The Negative Regulation Of Integrin AIIbb3 Platelet Signalling.
Funder
National Health and Medical Research Council
Funding Amount
$446,831.00
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 grant we 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.
Investigation Of Novel Mechanisms Regulating Platelet Reactivity During Haemostasis And Thrombosis
Funder
National Health and Medical Research Council
Funding Amount
$221,210.00
Summary
Platelets are small specialised blood cells that are critical for normal blood clotting and blood vessel repair following injury. We are studying the processes that enable platelets to stick to the site of vessel injury and to each other to form a stable blood clot. These very processes, when unchecked, are responsible for 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. Many factors control how big ....Platelets are small specialised blood cells that are critical for normal blood clotting and blood vessel repair following injury. We are studying the processes that enable platelets to stick to the site of vessel injury and to each other to form a stable blood clot. These very processes, when unchecked, are responsible for 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. Many factors control how big and how rapidly a blood clot grows and whether it becomes harmful enough to lead to a heart attack or stroke. One of these factors is the level of platelet 'reactivity' or 'stickiness' . We are working towards a better understanding of how platelet reactivity is regulated and how this dictates the potential of a blood clot to become harmful. This knowledge will not only increase our knowledge of blood clot formation in health and disease, but also help in the development of new therapies for the prevention of heart attack and stroke.Read moreRead less
Drug-induced Immune Thrombocytopenia: Understanding The Disease Mechanisms Is The Key To Better Treatment
Funder
National Health and Medical Research Council
Funding Amount
$509,550.00
Summary
Many very commonly used medications cause an allergic reaction in a small number of patients that receive them. The allergic reaction results in platelets being destroyed and puts the patients at risk of bleeding. The patient recovers slowly if the drug is stopped but there is no other treatment and no way to reverse the effect quickly if the patient starts to bleed. This project will try to understand the mechanism of the condition and test a potential treatment.
Regulation Of Platelet Adhesion By The GPIbalpha Cytoplasmic Tail
Funder
National Health and Medical Research Council
Funding Amount
$516,014.00
Summary
Platelets are small blood cells that play an essential role in the normal blood clotting process that stops bleeding following an injury to a blood vessel. In addition to their important role in preventing bleeding, they are also responsible for the development of harmful blood clots which can sometimes result in a fatal outcome in the form of a heart attack or a stroke. When platelets stick to sites of blood vessel injury they must respond very rapidly to ensure the formation of a stable blood ....Platelets are small blood cells that play an essential role in the normal blood clotting process that stops bleeding following an injury to a blood vessel. In addition to their important role in preventing bleeding, they are also responsible for the development of harmful blood clots which can sometimes result in a fatal outcome in the form of a heart attack or a stroke. When platelets stick to sites of blood vessel injury they must respond very rapidly to ensure the formation of a stable blood clot. Our research studies are aimed at understanding more closely the factors that regulate the adhesiveness of platelets, since this is an important deteminant not only in normal blood clot formation but also in the development of harmful blood clots (thrombosis). A better 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.Read moreRead less
Examining novel cell signalling in the regulation of platelet structure and function. Pharmaceutical inhibition of platelet function is the primary therapy for prevention of arterial thrombosis – the most common cause of death and disability in Australia. However, current therapies have limited efficacy. Defining platelet activation mechanisms in order to rationalise more effective antithrombotic approaches is the major focus of this research. This project describes the first studies to examine ....Examining novel cell signalling in the regulation of platelet structure and function. Pharmaceutical inhibition of platelet function is the primary therapy for prevention of arterial thrombosis – the most common cause of death and disability in Australia. However, current therapies have limited efficacy. Defining platelet activation mechanisms in order to rationalise more effective antithrombotic approaches is the major focus of this research. This project describes the first studies to examine the importance of a family of intracellular signalling enzymes, the Class II phosphoinositide 3-kinases, in platelet function. These studies will define the contribution of these enzymes to platelet production and function and will establish whether their inhibition is an attractive strategy for the prevention of arterial thrombosis.Read moreRead less
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