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.
Transcriptional Regulation Of Haematopoietic Stem Cell Development
Funder
National Health and Medical Research Council
Funding Amount
$566,470.00
Summary
Cancer initiating cells acquire stem cell characteristics and self renew within a supportive environment that helps maintain and propagate malignant tumours. Identifying the normal hierarchy of gene regulation within blood stem cells and designing therapies that target key transcription factors (proteins that control other genes) that are over expressed in cancer stem cells is the ultimate goal.
Manipulation Of Haematopoietic Stem Cell Niches To Improve Their Clinical Use
Funder
National Health and Medical Research Council
Funding Amount
$434,883.00
Summary
Haematopoietic stem cells (HSC) reside in adult bone marrow (BM) and make all blood and immune cells. HSCs can be damaged by chemotherapy leading to blood and BM failure. We have identified an adhesion molecule in the BM which regulates HSC behaviour. We anticipate that inhibiting this molecule will i) help minimise HSC damage during chemotherapy and ii) enhance the success of BM transplantation.
Cell Cycle Regulation, Haemopoietic Stem Cells And Myeloproliferation.
Funder
National Health and Medical Research Council
Funding Amount
$579,138.00
Summary
My research has focused on understanding how the process of cell division can result in different outcomes for adult blood stem cells. I am interested in determining the role of bone and blood vessels in the regulation of blood stem cells and in the development of blood diseases (myeloprolifertive disease). I will also determine the effects of changing the cell cycle with drugs to improve transplantation of blood stem cells.
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.
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 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.
Using Direct Reprogramming To Generate And Rejuvenate Haematopoietic Stem Cells
Funder
National Health and Medical Research Council
Funding Amount
$1,026,313.00
Summary
One of the greatest promises of regenerative medicine lies in our ability to reprogram any cell type of the body into any other cell type. Transdifferentiation is the conversion of one adult cell type to another and it is believed to be the next frontier in regenerative medicine therapies since it can be used in vivo for the direct conversion of one cell type into another. The outcomes of this grant will push the limits of these technologies to generate new regenerative medicine strategies.
Dementias affect a large number of Australians each year with the number of patients expected to triple by 2050. As such, there is need to develop a better model of this debilitating disorder to provide improved treatments. Mesenchymal stem cells, are relatively easy to obtain and grow, and are able to produce the key cell types in the brain. We can use these cells to identify the processes that control the production of brain cells, which will likely provide better treatment of this disease.