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Heparin Induced Thrombocytopenia (HIT): Further Characterization Of Disease Mechanism Will Improve Patient Treatment
Funder
National Health and Medical Research Council
Funding Amount
$456,484.00
Summary
Thrombus formation occurs as a side effect of heparin treatment in many patients. This condition is called Heparin Induced Thrombocytopenia (HIT). The clots may be stabilised by secretions from cells called neutrophils. In this project we will study this possibility using a mouse model of HIT and will explore therapeutic approaches to inhibit clot stabilisation.
Optimising Transfusion Support In Critical Illness And Haematological Malignancies
Funder
National Health and Medical Research Council
Funding Amount
$262,251.00
Summary
Blood transfusion is commonly used for patient care. Improving our understanding about how to best use blood and blood products and finding ways to reduce the need for transfusion have been identified as important areas of national research. This fellowship aims to investigate interventions to reduce bleeding and the need for transfusion and improve the use of blood transfusion in two patients groups who are major users of blood: critically ill patients and patients with blood cancers.
The mechanisms regulating expression and function of surface receptors on blood platelets are critical for understanding cardiovascular diseases involving aberrant platelet function, not only thrombotic diseases such as heart attack or stroke, but other pathology involving platelets including coagulopathy and autoimmune thrombocytopenia caused by anti-platelet antibodies. Improved diagnosis and therapeutic targeting of platelet-specific receptors mediating arterial thrombosis can save many lives ....The mechanisms regulating expression and function of surface receptors on blood platelets are critical for understanding cardiovascular diseases involving aberrant platelet function, not only thrombotic diseases such as heart attack or stroke, but other pathology involving platelets including coagulopathy and autoimmune thrombocytopenia caused by anti-platelet antibodies. Improved diagnosis and therapeutic targeting of platelet-specific receptors mediating arterial thrombosis can save many lives given the prevalence and severity of disease.Read moreRead less
The Function Of BHLH Factors In Adult Haemopoiseis
Funder
National Health and Medical Research Council
Funding Amount
$595,353.00
Summary
Understanding how genes control the behaviour of bone marrow stem cells is currently needed for improving recovery after chemotherapy or bone marrow transplantation and in the future, will aid the application of new stem cell-based therapies for human diseases such as leukaemia. This research will examine how 2 closely related genes control bone marrow stem cell growth and the decision between beocoming a red cell or a white cell.
Platelets are key blood elements that are essential for the prevention of bleeding in response to injury or infection. Overactive or spontaneously active platelets cause thrombosis and blood clot formation. My laboratory has identified new physiological pathways of activation of platelet metalloproteinases, the enzymes that regulate surface levels of the prothrombotic platelet receptors. By understanding this mechanism of receptor regulation, we can uniquely target platelet receptors in people w ....Platelets are key blood elements that are essential for the prevention of bleeding in response to injury or infection. Overactive or spontaneously active platelets cause thrombosis and blood clot formation. My laboratory has identified new physiological pathways of activation of platelet metalloproteinases, the enzymes that regulate surface levels of the prothrombotic platelet receptors. By understanding this mechanism of receptor regulation, we can uniquely target platelet receptors in people with prothrombotic pathologies.Read moreRead less
Blood clotting is dependent upon platelets. A decline in platelet number, or thrombocytopenia, is a life threatening condition that can result from various diseases or importantly as a side effect of chemotherapy. We are investigating the control of platelet production. A long term goal is to stimulate platelet production in patients by boosting the natural pathways or to generate platelet producing cells for transfusion from a patient's own skin cells by genetic reprogramming.
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.
Heparin-induced Thrombocytopenia And Thrombosis: Better Understanding Of Pathogenesis And Improving Diagnosis And Treatment
Funder
National Health and Medical Research Council
Funding Amount
$653,137.00
Summary
Heparin, a widely used drug, can cause an adverse effect which results in a fall of the platelet count and the development of serious thrombosis. This drug complication is mediated by an immune mechanism. This proposal aims to provide a better understanding of the disease mechanism. It also aims to develop a new test that will improve the diagnosis, and to produce a novel drug that will effectively suppress the immune reaction and improve the treatment.
The Regulation Of PI 3-kinase Second Messenger Molecules, PtdIns(3,4)P2 And PtdIns 3-P.
Funder
National Health and Medical Research Council
Funding Amount
$406,980.00
Summary
Cells respond to the external environment, hormones, and growth factors by generating messages inside the cell that send a signal to the nucleus that stimulates cell growth. One such signalling network is that produced by membrane lipids known as phosphoinositides. Enzymes that produce these signals are known as kinases. There has been considerable interest in the PI 3-kinase as the signals generated by this enzyme are increased in many human cancers. Inherited cancer syndromes have been describ ....Cells respond to the external environment, hormones, and growth factors by generating messages inside the cell that send a signal to the nucleus that stimulates cell growth. One such signalling network is that produced by membrane lipids known as phosphoinositides. Enzymes that produce these signals are known as kinases. There has been considerable interest in the PI 3-kinase as the signals generated by this enzyme are increased in many human cancers. Inherited cancer syndromes have been described that have lost the ability to switch off PI 3-kinase signals. The current project aims to investigate a recently identified enzyme called the 4-phosphatase that has the ability to terminate PI 3-kinase signals. Recent studies have shown this enzyme regulates cell growth. In addition key experiments have shown the enzyme is important as it may regulate certain strains of bacterial infection. This research proposal aims to investigate how the enzyme works to regulate these growth promoting signals. This may help us develop novel therapeutic strategies to control cell growth.Read moreRead less