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.
The BHLH Transcription Factor LYL1 In Normal And Leukemic Hematopoiesis
Funder
National Health and Medical Research Council
Funding Amount
$520,945.00
Summary
This project aims to understand how two closely related genes, called SCL and LYL1, work together to control the production of normal red blood cells and when abnormally expressed, cause cancer of the white blood cells. We will specifcially examine how LYL1 causes a specific type of leukemia in children and determine blocking the function of LYL1 will be a useful way to kill leukemia cells.
The Roles Of Retinoic Acid Receptors In Regulating Haemopoiesis And Bone
Funder
National Health and Medical Research Council
Funding Amount
$601,484.00
Summary
My research has shown that vitamin A is very important to the normal function of blood and bone cells. I will further explore the uses of vitamin A products to improve the treatment of patients with a range of different blood and bone diseases. These studies may lead to better treatments of patients with a wide range of blood cell diseases. It may also reveal better treatments for patients with bone diseases such as cancer and osteoporosis.
Endocytosis And Asymmetric Cell Division In Leukemia.
Funder
National Health and Medical Research Council
Funding Amount
$548,258.00
Summary
Self-renewal allows normal haematopoeitic stem cells to constantly replenish the blood system. Conversely, leukemia stem cells use self-renewal to propagate the disease, and utilise the quiescence phase to evade treatment eradication. We identified that the endocytic gene, Ap2a2 enhances haematopoeitic stem cell self-renewal. Through Ap2a2, we are now investigating the role of endocytosis and self-renewal in leukemia and ex vivo expansion of human haematopoietic stem cells.
Role Of Zeb2/Sip1 In Leukaemic Stem Cell Formation And Cancer Progression
Funder
National Health and Medical Research Council
Funding Amount
$655,174.00
Summary
T-cell acute lymphoblastic leukaemia (T-ALL) results from the abnormal development of T cells that are an important cell type in the body's immune system. Although the prognosis for T-ALL has improved remarkably over the last decade, for one out of five T-ALL cases the underlying genetic defects remain unresolved and are refractory to current therapies. This project aims to use both novel mouse models and human patient cell lines to better understand this disease and discover novel targets for f ....T-cell acute lymphoblastic leukaemia (T-ALL) results from the abnormal development of T cells that are an important cell type in the body's immune system. Although the prognosis for T-ALL has improved remarkably over the last decade, for one out of five T-ALL cases the underlying genetic defects remain unresolved and are refractory to current therapies. This project aims to use both novel mouse models and human patient cell lines to better understand this disease and discover novel targets for fighting this disease.Read moreRead less
Investigating The Gene And Gene Expression Differences In The Cells That Drive Leukemia Development And Relapse In Children With AML
Funder
National Health and Medical Research Council
Funding Amount
$388,612.00
Summary
Current treatments for AML are initially effective at killing the majority of leukemic cells, but the disease often comes back (relapses) due to rare cells that escape treatment and can regenerate the cancer (called leukemic stem cells or LSC for short). This project aims to determine if an individual patient has one, or many kinds of LSC and which kind of LSC is most likely to cause relapse. We believe that this knowledge will lead to new treatments that can target the cells that cause relapse.
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.
The Role Of Intracellular Uptake And Retention Of Abl Kinase Inhibitors In Modifying Clinical Response In CML
Funder
National Health and Medical Research Council
Funding Amount
$465,210.00
Summary
Imatinib is one of the first targeted anticancer drugs to be clinically developed. It is designed to inhibit the kinase activity of BCR-ABL, a mutant protein found in some cases of leukaemia, particularly chronic myeloid leukaemia. Blocking the kinase activity of BCR-ABL has proven to be highly effective therapy for most patients, achieving prolonged remissions and significantly improving survival. However resistance to imatinib is a problem, including failure to respond to imatinib, loss of res ....Imatinib is one of the first targeted anticancer drugs to be clinically developed. It is designed to inhibit the kinase activity of BCR-ABL, a mutant protein found in some cases of leukaemia, particularly chronic myeloid leukaemia. Blocking the kinase activity of BCR-ABL has proven to be highly effective therapy for most patients, achieving prolonged remissions and significantly improving survival. However resistance to imatinib is a problem, including failure to respond to imatinib, loss of response, and long term persistence of low levels of leukaemia. New ABL kinase inhibitors (AKIs) have been developed that are more potent than imatinib, but they also appear to be prone to resistance. One potentially important cause of resistance to AKIs is the ability of some leukaemic cells to modify their cellular pathways to reduce the effective concentration of the drug by either reducing its movement into the cell (influx) or increasing its movement out (efflux). We will investigate the mechanisms used by resistant leukaemic cells to reduce intracellular drug levels of these AKIs and test ways of countering these effects by blocking the proteins responsible for drug efflux or promoting drug influx. These studies will use our stored collections of leukaemic cells from responsive and resistant patients to determine the importance of specific influx and efflux pumps. It will help to identify patients where this form of resistance is limiting response. This may allow us to develop more effective AKIs that are less prone to these forms of drug resistance. We will also test whether other anti-cancer drugs have an impact on AKI drug transport because this could reduce the effectiveness of combination treatment. The effects on drug transport of concomitant administration of commonly used drugs together with AKIs will also be studied because this can reduce the effectiveness of AKis or in some cases improve their effectiveness by increasing their uptake and retention.Read moreRead less
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.