Investigate Novel Functional Roles For PI 3-kinases In Platelets.
Funder
National Health and Medical Research Council
Funding Amount
$537,215.00
Summary
Platelets are small blood cells which have a well defined role in blood clotting. There is a growing body of evidence that platelets play an important role in a broad range of inflammatory diseases, and we have identified a key role for the platelet PI3K enzyme in controlling the pro-inflammatory function of platelets. This grant will examine the importance of PI3K in health and disease, and examine the potential therapeutic benefits of inhibiting platelet PI3K.
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
Zbtb11 is a druggable protein that is mis-expressed in blood cancers - second biggest cause of cancer death in Australia - and liver cancer, third leading cause of death from cancer worldwide. We have found that it interacts with 2 other proteins with potential roles in these diseases. Our studies examine the nature of these Zbtb11-partner interactions and their particular consequences for blood disorders. Zbtb11 contributions to disease development will be a target for novel disease therapy.
We want to understand more about the control of blood cell formation and the development of leukaemia. We have discovered one gene that is very important in both these processes. It is the most common genetic abnormality involved in causing human T-cell leukaemia and we have recently shown that it is absolutely required for the development of all blood cells within an animal. We wish to take these observations further so that we can ultimately understand how a gene important in blood cell format ....We want to understand more about the control of blood cell formation and the development of leukaemia. We have discovered one gene that is very important in both these processes. It is the most common genetic abnormality involved in causing human T-cell leukaemia and we have recently shown that it is absolutely required for the development of all blood cells within an animal. We wish to take these observations further so that we can ultimately understand how a gene important in blood cell formation can also be important in causing leukaemia. To address this we will generate new models of blood cell development.Read moreRead less
Investigating The Gene And Gene Expression Differences In The Cells That Drive Leukemia Development And Relapse In Children With AML
Funder
National Health and Medical Research Council
Funding Amount
$388,612.00
Summary
Current treatments for AML are initially effective at killing the majority of leukemic cells, but the disease often comes back (relapses) due to rare cells that escape treatment and can regenerate the cancer (called leukemic stem cells or LSC for short). This project aims to determine if an individual patient has one, or many kinds of LSC and which kind of LSC is most likely to cause relapse. We believe that this knowledge will lead to new treatments that can target the cells that cause relapse.
Investigate The Role Of PAF And CD40 Ligand In Regulating The Proinflammatory Properties Of Platelets
Funder
National Health and Medical Research Council
Funding Amount
$507,270.00
Summary
The cells of the blood play an important role in maintaining healthy blood vessels. We are interested in two types of blood cells, platelets and leukocytes, which together play a key role in vessel maintenance, by promoting blood clot formation and vessel wall repair following injury. However, while critical for normal blood vessel maintenance, these cells have also been demonstrated to contribute to disease states including atherosclerosis, thrombosis and inflammatory airway diseases. Underlyin ....The cells of the blood play an important role in maintaining healthy blood vessels. We are interested in two types of blood cells, platelets and leukocytes, which together play a key role in vessel maintenance, by promoting blood clot formation and vessel wall repair following injury. However, while critical for normal blood vessel maintenance, these cells have also been demonstrated to contribute to disease states including atherosclerosis, thrombosis and inflammatory airway diseases. Underlying the function of both blood cell types is their ability to stick (or adhere) to each other. However the way in which they coordinate this adhesion is very complex. New information from our laboratory has demonstrated that the sticky behaviour of each cell type is spatially and temporally regulated, and may involve may factors both inside and outside of the cells themselves. Our studies aim to define the key components regulating the 'stickiness' of these blood cells, in order to undertand how they contribute to maintaining healthy vessel walls, but also how their stickiness may also contribute to the promotion of diseased vessels. This information will not only increase our knowledge of the factors that regulate blood clot formation, but may also assist in the development of new therapies to prevent and-or treat vessel disease.Read moreRead less
A Phase I Study Of Autologous CD19 Specific Chimeric Antigen Receptor T-cells For Therapy Of Relapsed And Refractory B-cell Leukaemia And Lymphoma (The Auto-CAR19 Trial).
Funder
National Health and Medical Research Council
Funding Amount
$584,666.00
Summary
Most people with leukaemia and lymphoma who relapse early after chemotherapy die of their disease. Inserting special genes into immune cells can enable them to kill leukaemia and lymphoma and has led to dramatic cures, but the cost of the viral vectors used to make these cells is prohibitively expensive. We will make leukaemia and lymphoma specific immune cells from patients using an inexpensive non-viral system, then administer the immune cells to patients to assess their safety and efficacy.