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 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.
Role Of The Hypoxia-inducible Transcription Factor HIF-1a In Controlling Haematopoietic Stem Cell Fate
Funder
National Health and Medical Research Council
Funding Amount
$586,428.00
Summary
Haematopoietic stem cells (HSCs) reside in the bone marrow (BM) and make all immune and blood cells. We have found that, in the areas of the BM where HSC normally live, the level of oxygen is very low (hypoxia) and decreases even further when HSC are forced to move into the blood in order to be collected for transplantation. This project is to better understand how oxygenation of the BM controls HSC behaviour and properties, and to evaluate its impact on HSC transplantation.
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.
Targeting Disease-initiating Cells In Myeloproliferative Neoplasms
Funder
National Health and Medical Research Council
Funding Amount
$477,170.00
Summary
The myeloproliferative neoplasms (MPN) are a related group of blood disorders. Despite the advent of targeted therapies, patients have significant ongoing morbidity, mortality and financial cost. A key reason underlying the persistence of disease is the presence of a stem cell pool that is resistant to targeted therapy. Clinical data has suggested that interferon may target these disease stem cells. We propose to use in vivo, validated disease models to investigate the role of interferon in MPN.
Mechanisms By Which Endothelial Selectins Regulate Normal And Malignant Stem Cell Fate
Funder
National Health and Medical Research Council
Funding Amount
$708,742.00
Summary
Hematopoietic stem and progenitor cells (HSPC) reside in the bone marrow (BM) and make all the cells of the blood system. We have found a molecule in the BM which when increased during inflammation, awakens normal HSPC. We previously showed this molecule also helps leukaemia and other cancer stem cells resist chemotherapy. We have now identified the mechanism why. These proposed studies open new therapeutic avenues to sensitise cancer stem cells to therapy enabling long-term cure.
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.
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.
Recipient Bone Marrow Macrophages Contribute To Haematopoietic Stem Cell Transplantation Success
Funder
National Health and Medical Research Council
Funding Amount
$608,906.00
Summary
We propose an innovative approach to reduce risk and increase success of blood stem cell transplantation. We will determine whether a specialized cell within the transplant patient is required for donor stem cells to successfully take up residence and recreate the blood and immune system. We will test whether fortifying these specialized cells will improve transplantation outcomes, consequently increasing the number of transplants that can proceed and reducing potentially fatal complications.