Investigating The Contribution Of Distinct Mitochondrial Cell Death Pathways To Platelet Survival And Function
Funder
National Health and Medical Research Council
Funding Amount
$635,247.00
Summary
Platelets are small blood cells that form clots to stop bleeding. We have found new and unexpected roles for 2 distinct pathways that regulate cell death in the process of blood clot formation. We will study the precise role of these pathways in blood clot formation, and determine whether they may also regulate the survival of platelets stored by the blood bank for transfusion. These studies will provide new insight into the role of cell death pathways in blood clot formation, and may help to im ....Platelets are small blood cells that form clots to stop bleeding. We have found new and unexpected roles for 2 distinct pathways that regulate cell death in the process of blood clot formation. We will study the precise role of these pathways in blood clot formation, and determine whether they may also regulate the survival of platelets stored by the blood bank for transfusion. These studies will provide new insight into the role of cell death pathways in blood clot formation, and may help to improve current protocols for storing plateletsRead moreRead less
Regulatory T Cell Therapy For Prevention Of Graft Versus Host Disease
Funder
National Health and Medical Research Council
Funding Amount
$765,299.00
Summary
Graft versus host disease (GVHD) is a potentially fatal complication of bone marrow stem cell transplantation for leukaemia and lymphoma. In an animal model of GVHD, we have recently shown 100% effectiveness of treatment with a donor immune cell population, regulatory T cells. We will determine how this therapy works in the animal model. We will use a new technique, mass cytometry, to analyse patient blood samples in preparation for developing regulatory T cell therapy for GVHD.
Microenvironmental Regulation Of Blood Cells By Retinoic Acid Receptor Gamma.
Funder
National Health and Medical Research Council
Funding Amount
$958,428.00
Summary
Vitamin A deficiency causes profound effects in humans, with anaemia and an inability to fight infection being consequences of vitamin A deficiency on blood cells. We have evidence that these effects of vitamin A deficiency occur via one of the receptors for vitamin A. Furthermore, these effects are due to changes in the non-blood cells that help to make blood cells. By understanding how this occurs we may identify better treatments for patients with impaired immune systems.
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.
IL-6 As The Key Inflammatory Mediator Controlling GVHD
Funder
National Health and Medical Research Council
Funding Amount
$592,049.00
Summary
Allogeneic haematopoietic stem cell transplantation (SCT) is a curative treatment for blood cancers. Graft-versus-host disease (GVHD) is a major limitation which occurs when the newly transplanted immune system mounts a rejection response against the recipient and is responsible for the death of up to 40% of transplant recipients. These studies will optimize a new approach to prevent GVHD focusing on a protein called interleukin-6. Ultimately, it is anticipated such approaches will improve the o ....Allogeneic haematopoietic stem cell transplantation (SCT) is a curative treatment for blood cancers. Graft-versus-host disease (GVHD) is a major limitation which occurs when the newly transplanted immune system mounts a rejection response against the recipient and is responsible for the death of up to 40% of transplant recipients. These studies will optimize a new approach to prevent GVHD focusing on a protein called interleukin-6. Ultimately, it is anticipated such approaches will improve the overall survival of patients with blood cancers.Read moreRead less
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
A Newly Identified Role For 14-3-3zeta Protein In Thrombosis And Platelet Procoagulant Activity
Funder
National Health and Medical Research Council
Funding Amount
$556,327.00
Summary
Cardiovascular disease, including heart attack and stroke is the major cause of death globally, and is responsible for the death of 50,000 Australians each year. Platelet activation and blood coagulation play an important role in these diseases and we have discovered that a protein called 14-3-3 zeta is important in the processes that result in thrombosis. We are studying the mechanisms by which this protein contributes to life-threatening platelet activation with the aim of developing new and m ....Cardiovascular disease, including heart attack and stroke is the major cause of death globally, and is responsible for the death of 50,000 Australians each year. Platelet activation and blood coagulation play an important role in these diseases and we have discovered that a protein called 14-3-3 zeta is important in the processes that result in thrombosis. We are studying the mechanisms by which this protein contributes to life-threatening platelet activation with the aim of developing new and more effective anti-thrombotic drugs.Read moreRead less
The Role Of Autophagy In Stem Cell Transplantation
Funder
National Health and Medical Research Council
Funding Amount
$956,055.00
Summary
Hematopoietic stem cell transplantation (SCT) is the only curative therapy for most blood cancers. The curative property of SCT relates to the graft-versus-leukaemia effect, which eradicates any remaining cancer after SCT. Unfortunately the success of SCT is significantly limited by three procedural complications: GVHD, graft failure, and infection. Our research aims to improve our understanding how these complications arise to develop new therapies that can be translated to clinical practice.
The Interplay Between IL-6 And GVHD On Anti-viral And Anti-leukaemic Immunity
Funder
National Health and Medical Research Council
Funding Amount
$489,376.00
Summary
Bone marrow transplantation can cure leukaemia but infection, graft-versus-host disease (GVHD) and leukaemia relapse remain challenging problems. We recently completed an early phase clinical study on GVHD prevention using interleukin-6 blockade. Interestingly, the rate of virus reactivation was also lower. This project will use a newly developed mouse model and stored clinical samples to understand the underlying mechanism and whether it also has an impact on anti-leukaemic immunity.
Redirecting T-cells For Immunotherapy Of Leukaemia And Lymphoma By The Expression Of A CD19-specific Chimeric Antigen Receptor Using The PiggyBac Transposon Gene Modification System
Funder
National Health and Medical Research Council
Funding Amount
$374,876.00
Summary
Most lymphomas respond to therapy but then relapse. Immune cells can attack and kill virus related lymphomas. However, most lymphomas are NOT virus related. We will create immune cells targeting these virus negative lymphomas by inserting artificial receptors into the immune cells. These receptors attach to the lymphoma and activate the immune cells. The immune cells will home to the lymphoma, kill lymphoma cells and persist in the body for many years, preventing lymphoma relapse.