Blood clotting is the underlying cause of heart attacks and strokes. We have discovered that the protein, ERp5, is essential for normal blood clotting. Our preliminary findings indicate that ERp5 controls the function of blood platelets in clotting. Our overall aim is to elucidate how ERp5 regulates platelet function. It is crucial that we understand how ERp5 functions in blood clotting if we are to effectively target it in disease.
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.
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
The Anti-thrombotic Potential Of Immunoreceptors In Platelet Thrombus Formation
Funder
National Health and Medical Research Council
Funding Amount
$522,773.00
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 immunoreceptors expressed on the surface of platelets modulate th ....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 immunoreceptors expressed on the surface of platelets modulate the function of platelet collagen interactions involving collagen GPVI receptor, the low affinity IgG receptor, FcgammaRIIa and the major platelet integrin, integrin alphaIIbbeta3. The aims of this work will define the role of these receptors in platelet aggregation 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
Tetraspanins Serve As Molecular Facilitators To Regulate Platelet Thrombus Formation
Funder
National Health and Medical Research Council
Funding Amount
$589,544.00
Summary
Platelets are small fragments of megakaryocytes that circulate in the blood stream. They 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. We have discovered that tetraspanins serve to regulate platelet glycoproteins including integrin alphaIIbbeta, P2Y12 and thrombosis.