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Allogeneic stem cell transplantation (SCT) remains the most effect curative treatment for patients with a number of malignant conditions, especially leukemia. The ability to cure leukemia by this procedure relates to a process known as Graft-versus-Leukaemia effects (GVL) which ocurrs when the newly transplanted stem cells (which includes the immune system) recognises the leukemia as foreign and mounts an immune attack against it. These studies will focus on the effect of a cellular pathway invi ....Allogeneic stem cell transplantation (SCT) remains the most effect curative treatment for patients with a number of malignant conditions, especially leukemia. The ability to cure leukemia by this procedure relates to a process known as Graft-versus-Leukaemia effects (GVL) which ocurrs when the newly transplanted stem cells (which includes the immune system) recognises the leukemia as foreign and mounts an immune attack against it. These studies will focus on the effect of a cellular pathway invilving NKT cells that preliminary data suggests is critical to the development of GVL. Methods to augment this activation pathway will be studied in preclinical models that may then be studied in clinical trials with the aim of improving the outcome of patients transplanted for leukemias.Read moreRead less
Regulatory Dendritic Cells For The Prevention And Treatment Of Graft-versus-Host Disease.
Funder
National Health and Medical Research Council
Funding Amount
$165,250.00
Summary
Allogeneic bone marrow transplantation (BMT) remains the most effect curative treatment for patients with a number of malignant conditions, especially leukemia. Graft-versus-Host Disease (GVHD) ocurrs when the newly transplanted bone marrow (which includes the immune system) recognises the transplant recipient as foreign and mounts an immune attack against patient tissues. GVHD is the major complication of BMT and is responsible for the death of up to half of the patients who receive this proced ....Allogeneic bone marrow transplantation (BMT) remains the most effect curative treatment for patients with a number of malignant conditions, especially leukemia. Graft-versus-Host Disease (GVHD) ocurrs when the newly transplanted bone marrow (which includes the immune system) recognises the transplant recipient as foreign and mounts an immune attack against patient tissues. GVHD is the major complication of BMT and is responsible for the death of up to half of the patients who receive this procedure. These studies will focus on the ability of a newly defined type of white blood called a regulatory dendritic cell to prevent this complication and avoid the requirement for BMT patients to take drugs that suppress their immune system.Read moreRead less
Neural Transplantation Of Human Bone Marrow Stromal Cells To Replace Oligodendrocytes Lost In Multiple Sclerosis
Funder
National Health and Medical Research Council
Funding Amount
$249,750.00
Summary
Multiple sclerosis is a disease of the central nervous system in which myelin (an insulative coating around the axons of neurons) and oligodendrocytes (the cells that produce myelin) are attacked and damaged by an unknown process. This damage is referred to as demyelination and results in a blocking or weakening of nerve signal conduction. Some of the symptoms of multiple sclerosis are weakness, tingling or numbness of limbs, and double vision or visual loss. One strategy to repair the demyelina ....Multiple sclerosis is a disease of the central nervous system in which myelin (an insulative coating around the axons of neurons) and oligodendrocytes (the cells that produce myelin) are attacked and damaged by an unknown process. This damage is referred to as demyelination and results in a blocking or weakening of nerve signal conduction. Some of the symptoms of multiple sclerosis are weakness, tingling or numbness of limbs, and double vision or visual loss. One strategy to repair the demyelination is to transplant cells into the damaged brain that can replace the damaged oligodendrocytes and remyelinate. Studies have shown that oligodendrocyte progenitor cells and neural stem cells transplanted into the brain can mature into oligodendrocytes and myelinate axons. However these cells are very difficult to obtain, the best source is foetal terminations but the use of such tissue raises ethical and practical problems. Recently cells found in adult bone marrow, called marrow stromal cells, have been shown to differentiate into neural cells when transplanted into the brain. This raises the possibility that sufferers of multiple sclerosis may be able to have marrow stromal cells taken from their bone marrow and then transplanted into their brains to replace their damaged oligodendrocytes. Our study will investigate the differentiation of marrow stromal cells into oligodendrocytes and determine if marrow stromal cells transplanted into demyelinated mouse brain can replace damaged oligodendrocytes and remyelinate areas of damage.Read moreRead less
Haematopoietic Stem Cells From Human Pluripotent Stem Cells: The Future Of Bone Marrow Transplantation
Funder
National Health and Medical Research Council
Funding Amount
$763,845.00
Summary
Blood stem cell transplantation is a vital therapy for patients with leukaemia following chemotherapy or for patients with bone marrow failure. Because many patients lack a donor, there is a need for an alternate source of stem cells. My laboratory will make blood stem cells from human pluripotent stem cells that will treat patients needing a transplant and will be a useful research tool to help us to understand what goes wrong in the blood system in a range of illnesses.
The Role Of Ap2a2 In Self-renewal Of Haematopoietic And Leukemic Stem Cells
Funder
National Health and Medical Research Council
Funding Amount
$579,171.00
Summary
The daily replenishment of the blood system is dependent on the blood stem cell. A unique property of these stem cells is self-renewal where the stem cell function is preserved, whilst other daughter cells continue to divide. Our research investigates the molecular mechanisms that regulate stem cell self-renewal. This work has potential clinical application on at least two levels: expansion of stem cells for transplantation, and for attacking abnormal cancer cell self-renewal pathways.
Haematopoietic Stem Cell Glycome Regulates Outcome Of Niche Interactions
Funder
National Health and Medical Research Council
Funding Amount
$913,729.00
Summary
Hematopoietic stem cells (HSC) reside in the bone marrow (BM) and make all the cells of the blood system. We have found a factor in the BM which when blocked, puts normal HSC to sleep helping them survive chemotherapy. This means cancer patients should suffer less side-effects from their therapy. This factor also helps leukaemia stem cells (LSC) resist chemotherapy. Inhibitors may a) reduce patient mortality caused by chemotherapy and b) sensitise LSC to chemotherapy enabling long-term cure.
The Role Of Oligodendrocytes In Frontotemporal Dementia
Funder
National Health and Medical Research Council
Funding Amount
$625,292.00
Summary
Dementia affects 35.6 million people world-wide; this number is projected to double every 20 years. Frontotemporal dementia (FTD) is the second most common type and has been found to have similar cause and pathology to common neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS). We ultimately require treatments to slow, stop and repair the damaged brain of FTD patients and this is only possible by understanding the mechanisms involved in the onset and progression of disease.
Hematopoietic Transplants From Autologous Pluripotent Cell Sources
Funder
National Health and Medical Research Council
Summary
This proposal investigates the utility of two types of patient-derived stem cells for transplantation into blood. These are induced pluripotent stem cells that are reprogrammed from specialized tissues such as skin cells, and stem cells derived using the genetic material of oocytes or sperm only ( one-parent embryos). Using the mouse, we are looking at the ability of these cells to form normal blood lineages after transplantation, and to repair blood in a mouse model for beta-thalassemia.