Investigating The Link Between Oxidative Stress And Biomechanical Integrin Activation In Diabetes
Funder
National Health and Medical Research Council
Funding Amount
$653,742.00
Summary
Diabetes represents a serious healthcare problem globally. A large proportion of deaths associated with diabetes can be attributed to the development of blood clots in the circulation of the heart and brain (heart attack/stroke). The blood clotting mechanism is ‘hyperactive’ in diabetes, although the reason for this is not well defined. In this proposal we will investigate a new mechanism promoting blood clots, and will investigate innovative approaches to reduce this clotting mechanism.
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.
Investigating A Potential New Treatment For Stroke
Funder
National Health and Medical Research Council
Funding Amount
$878,522.00
Summary
Blood clots blocking blood flow to the brain (stroke) are a major cause of death and disability. Safety concerns limit approved therapies to a small subset of patients, highlighting an urgent need for safer, more effective drugs. Our studies show that inhibitors of the enzyme PI3Kbeta increase blood clot permeability, increasing clot ‘dissolvability’, without increased bleeding. This raises the possibility that PI3Kbeta inhibitors may represent a safe and effective adjuvant therapy for stroke.
Investigating A Novel Role For The Haemopoietic Growth Factor Receptor, C-Mpl, In Regulating Shear-dependent Platelet Adhesive Function
Funder
National Health and Medical Research Council
Funding Amount
$570,294.00
Summary
Platelets play a critical role in blood clot formation, with low platelet numbers leading to bleeding while excessive clot formation can cause heart attack and stroke. Platelets must ‘stick’ to injured blood vessels under blood flow (shear). We have discovered that the growth factor, c-Mpl, can regulate shear-dependent platelet sticking by controlling receptor ‘shedding’ from the cell surface. We will investigate how c-Mpl performs this new role, and examine platelet function in patients with my ....Platelets play a critical role in blood clot formation, with low platelet numbers leading to bleeding while excessive clot formation can cause heart attack and stroke. Platelets must ‘stick’ to injured blood vessels under blood flow (shear). We have discovered that the growth factor, c-Mpl, can regulate shear-dependent platelet sticking by controlling receptor ‘shedding’ from the cell surface. We will investigate how c-Mpl performs this new role, and examine platelet function in patients with myeloproliferative disease who have reduced c-Mpl.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
Investigation Of Activating Signals Transmitted During Platelet Aggregation
Funder
National Health and Medical Research Council
Funding Amount
$267,750.00
Summary
The blood platelet is a specialized adhesive cell that plays a critical role in the normal blood clotting process through its ability to rapidly adhere to sites of vascular damage. Upon injury to a blood vessel, platelets undergo a number of internal signalling process and strucural changes that allow them to rapidly adhere to the area of damage. Following this initial adhesion process, platelet-platelet interactions occur leading to the development of a stable blood clot. Our research studies a ....The blood platelet is a specialized adhesive cell that plays a critical role in the normal blood clotting process through its ability to rapidly adhere to sites of vascular damage. Upon injury to a blood vessel, platelets undergo a number of internal signalling process and strucural changes that allow them to rapidly adhere to the area of damage. Following this initial adhesion process, platelet-platelet interactions occur leading to the development of a stable blood clot. Our research studies are aimed at understanding more closely the factors that regulate platelet-platelet interactions during the course of blood clot formation, since this is an important determinant not only of normal clot formation, but also in the development of harmful blood clots (thrombi) associated with the onset of diseases such as heart attack and stroke. Our particular focus is on the way in which platelets communicate to one another during the course of platelet thrombus development. Particulary, we are interested in the role of calcium as a signal mediating platelet-platelet communication. We believe that the transmission of these calcium signals may be the key signaling mediator of blood clot formation and normal haemostasis.Read moreRead less
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 The Role Of The GPIb/V/IX-filamin-1 Interaction In Regulating Platelet Function In Vivo
Funder
National Health and Medical Research Council
Funding Amount
$267,750.00
Summary
Platelets play an essential role in blood clotting and blod vessel repair. Upon injury to a blood vessel, platelets rapidly adhere to the area of damage where they undergo dramatic changes in their shape and internal structure that facilitates spreading over the area of injury and subsequent 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 determinant not only in norm ....Platelets play an essential role in blood clotting and blod vessel repair. Upon injury to a blood vessel, platelets rapidly adhere to the area of damage where they undergo dramatic changes in their shape and internal structure that facilitates spreading over the area of injury and subsequent 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 determinant not only in normal blood clot formation but also in the development of harmful blood clots (thrombosis) associated with the development of diseases such as heart attack and stroke. Our particular focus is on the interaction between adhesion receptors on the surface of the platelet and components of the intracellular platelet structure referred to as the cytoskeleton and how this interaction might regulate the reactivity of platelets and their ability to adhere to blood vessels. We believe this may be an important mechanism that regulates platelet adhesion and notmal blood clotting.Read moreRead less
Redefining The Pro-thrombotic Mechanism Of Von Willebrand Factor
Funder
National Health and Medical Research Council
Funding Amount
$750,005.00
Summary
Blood clotting is the underlying cause of heart attacks and strokes. The blood protein, von Willebrand factor, is a critical player in blood clotting and impairment of its function is life threatening. We have discovered that there are three forms of VWF in human blood that have different functions in blood clotting. Characterisation of these different forms will likely lead to new blood clotting diagnostics and improved therapies.
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