A Virtual Map Of Haematopoiesis Using Cellular Barcoding
Funder
National Health and Medical Research Council
Funding Amount
$329,149.00
Summary
We have different types of infection-fighting white blood - the soliders of the immune system. They can all grow from a single stem cell like a seed grows into a tree. So, by understanding this complex process, new and better therapies for cancer, organ transplantation and infectious disease are constantly emerging. I aim to use a cutting-edge technology called ‘cellular barcoding’ to answer some of the age-old questions about how stem cells grow into white blood cells.
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.
Antibody-mediated Dendritic Cell Depletion To Attenuate GVHD
Funder
National Health and Medical Research Council
Funding Amount
$434,510.00
Summary
Not all patients with leukemia will be cured by chemotherapy. Stem cell transplantation improves their chances of survival. Stem cell transplantation requires intensive chemotherapy and radiotherapy to eradicate the underlying disease and infusion of healthy stem cells to provide an anti-leukemic effect and normal blood cells. Recovery from transplantation is not straightforward. Recovery can be hampered by the immunological reaction of the donor cells against the patient (Graft versus Host Dise ....Not all patients with leukemia will be cured by chemotherapy. Stem cell transplantation improves their chances of survival. Stem cell transplantation requires intensive chemotherapy and radiotherapy to eradicate the underlying disease and infusion of healthy stem cells to provide an anti-leukemic effect and normal blood cells. Recovery from transplantation is not straightforward. Recovery can be hampered by the immunological reaction of the donor cells against the patient (Graft versus Host Disease [GVHD]), despite immunosuppression. GVHD produces serious damage to the internal organs and lining of the mouth and gut. Recovery can also be circumvented by leukemic relapse. GVHD is associated with an increased risk of death and dying after transplantation. To date therapy for GVHD has relied on eliminating the T cells that cause the disease. However for T cells to cause damage they must first be primed with antigen presented on activated dendritic cells. The intensive conditioning therapy required to eradicate the underlying disease before transplantation also activates dendritic cells. Our project seeks to investigate the effects of lethal and non-lethal conditioning on dendritic cells with the aim of validating the use of antibodies designed to deplete activated dendritic cells as therapy for graft versus host disease.Read moreRead less
The Translation Of Dendritic Cell Biology Into Clinical Practice
Funder
National Health and Medical Research Council
Funding Amount
$3,674,406.00
Summary
This Program combines world recognized expertise in the science of immunology and the blood system, with top Australian expertise in the practice of bone marrow transplantation and the treatment of hematological malignancies. Its vision is to study the biology of dendritic cells, which are the specialized white cells that initiate the immune response, and then, to apply this knowledge to the design and introduction of novel diagnostic and therapeutic immune strategies, to improve the survival of ....This Program combines world recognized expertise in the science of immunology and the blood system, with top Australian expertise in the practice of bone marrow transplantation and the treatment of hematological malignancies. Its vision is to study the biology of dendritic cells, which are the specialized white cells that initiate the immune response, and then, to apply this knowledge to the design and introduction of novel diagnostic and therapeutic immune strategies, to improve the survival of patients with leukaemia, lymphoma and multiple myeloma.Read moreRead less
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.
Characterization Of HOXA-expressing Human Haematopoietic Cells Generated From Embryonic Stem Cells
Funder
National Health and Medical Research Council
Funding Amount
$622,464.00
Summary
Blood stem cell transplants are used for treating a range of human blood disorders such as leukaemias. However, for many patients, suitable donors cannot be found. We are searching for ways in which embryonic stem cells can be turned into blood stem cells in the laboratory to provide a new source of these cells that could then be used to treat patients.
Production Of Large Scale Erythroid Progenitor Cultures From Human Embryonic Stem Cells
Funder
National Health and Medical Research Council
Funding Amount
$396,718.00
Summary
Transfusion of fresh red blood cell units of the correct blood type into patients can be life saving. However, access to units of the correct blood type is often limited due to limited supply of donor blood and its short shelf life creating the need for a constant donor blood supply. We propose to develop a system that allows us to generate unlimited numbers of human red blood cells in a culture dish which we will derive from differentiating human embryonic stem cell lines.
I am a hematologist with expertise in the science of immunology and clinical experience in bone marrow transplantation and the treatment of hematological malignancies. My vision is to study the biology of dendritic cells, which are the specialized white cells that initiate the immune response, and then, to apply this knowledge to the design and introduction of novel diagnostic and therapeutic immune strategies, to improve the survival of patients with leukemia, lymphoma and multiple myeloma.
Bone Marrow Endothelial Stem Cells Have The Capacity To Form Both The Endothelial And Haemopoietic Hierarchies
Funder
National Health and Medical Research Council
Funding Amount
$1,452,856.00
Summary
Blood cell formation is hierarchically organised; with hemopoietic stem cells (HSC) responsible for producing mature circulating blood cells. HSC reside in marrow near blood vessel cells. Although these play a key role in HSC regulation their origin in adults is poorly understood. We have demonstrated the existence of adult marrow vessel stem cells at the apex of a parallel hierarchy. Our objective is to characterise these in mice and humans and determine their role in blood malignancies.
Role Of The Ets-family Transcription Factor Erg In Haematopoiesis
Funder
National Health and Medical Research Council
Funding Amount
$100,621.00
Summary
Development of blood cells is controlled by specific molecules called transcription factors. Transcription factors are important in developing mature white cells, red cells and platelets from blood stem cells. We have discovered that a transcription factor, Erg, is important in control of blood stem cells and blood cell development as well as being implicated in human cancers, including acute leukaemia. This project will characterise how this molecule is involved in these specific processes.