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
Cell Therapy To Prevent And Treat Graft-versus-host Disease After Allogeneic Haematopoietic Stem Cell Transplantation
Funder
National Health and Medical Research Council
Funding Amount
$260,302.00
Summary
In bone marrow transplantation, donor immunity can fight the cancer but can also attack healthy tissues, causing graft-versus-host disease (GVHD). We will use two types of cell therapy to treat GVHD. The first study will use a safety switch called inducible capase 9 (iCasp9) to enable the donor immune cells to be rapidly eliminated if GVHD occurs. The second study will use regulatory T cells to treat patients with chronic GVHD. If successful, these treatment approaches will make transplantation ....In bone marrow transplantation, donor immunity can fight the cancer but can also attack healthy tissues, causing graft-versus-host disease (GVHD). We will use two types of cell therapy to treat GVHD. The first study will use a safety switch called inducible capase 9 (iCasp9) to enable the donor immune cells to be rapidly eliminated if GVHD occurs. The second study will use regulatory T cells to treat patients with chronic GVHD. If successful, these treatment approaches will make transplantation safer.Read 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.
Molecular And Cellular Mechanisms Of Skeletal Disease Mediated By Plasma Cell Dyscrasias
Funder
National Health and Medical Research Council
Funding Amount
$432,750.00
Summary
Osteolytic and osteosclerotic lesions of bone are common sequelae of primary and secondary bone cancers, including cancers of hematological origin. There is now strong evidence that tumor cells perturb the local balance between bone resorption and formation, and in cases of osteolysis, cause increased osteoclast (OC)-mediated bone resorption without a matching amount of bone formation. This proposal arises from our extensive clinical and basic science experience with multiple myeloma (MM) in add ....Osteolytic and osteosclerotic lesions of bone are common sequelae of primary and secondary bone cancers, including cancers of hematological origin. There is now strong evidence that tumor cells perturb the local balance between bone resorption and formation, and in cases of osteolysis, cause increased osteoclast (OC)-mediated bone resorption without a matching amount of bone formation. This proposal arises from our extensive clinical and basic science experience with multiple myeloma (MM) in addition to other skeletal tumors, and our strong background in both OC and osteoblast biology. MM is a hematological malignancy characterised by plasma cell dyscrasia, which typically causes progressive and severe destruction of the skeleton, with accompanying bone pain, fracture and finally, hypercalcaemia of malignancy. Two related diseases, MGUS and POEMS, have been chosen for study because of their key similarities and differences with MM, and are likely to shed new light on the activities of MM in the bone. MGUS does not cause identifiable bone defects, whereas POEMS can give rise to both osteolytic and osteosclerotic lesions. Comparison of these conditions will uniquely enable us to examine why these seemingly related neoplasms are able to mediate disparate skeletal disease states. Primarily, and since there are few curative therapies for MM at present, our proposed studies are designed to identify targets for therapy that will treat the most serious manifestation of this disease, namely its destruction of bone tissue.Read moreRead less