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.
Acute Lymphoblastic Leukemia And The Bone Marrow Microenvironment
Funder
National Health and Medical Research Council
Funding Amount
$420,872.00
Summary
This research aims to identify new drugs for the treatment of childhood and adult acute lymphoblastic leukemia (ALL). We have identified drugs that interfere with interactions between the bone marrow and leukemic cells and hypothesise that these will increase the potency of currently used chemotherapy. We will test these agents in animal models of human leukemia. By analysing the effects of these new drugs we will also understand how we can further improve treatments.
The Role Of Cell Cycle Control In Haemopoietic Stem Cell Fate Decisions.
Funder
National Health and Medical Research Council
Funding Amount
$390,974.00
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.
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.
Microenvironmental Impact In The Treatment Of Acute Lymphoblastic Leukemia
Funder
National Health and Medical Research Council
Funding Amount
$621,458.00
Summary
Acute lymphoblastic leukemia remains one of the leading causes of death in children and outcomes for adults with this disease remain poor. This project examines how manipulation of the environment where leukemia arises can be used to therpaeutic advancage. Acute lymphoblastic leukemia cells are highly dependent on the support provided by bone marrow cells but the mechanisms are not well understood. Disrupting signals from the bone marrow cells has potential as a therapeutic strategy.
Manipulation Of Haematopoietic Stem Cell Niches To Improve Therapeutic Outcomes
Funder
National Health and Medical Research Council
Funding Amount
$451,716.00
Summary
My aim is to understand how stem cells are naturally regulated by the body. My central hypothesis is that local environment (niche) factors largely govern stem cell behaviour. Identification and manipulation of these factors will offer a novel therapeutic opportunity to improve the clinical use of normal haematopoietic stem cells to improve transplantation success, as well as sensitise leukaemia cells to chemotherapy.
CXCR4 Antagonists In Acute Lymphoblastic Leukemias In NOD/SCID Mice
Funder
National Health and Medical Research Council
Funding Amount
$505,500.00
Summary
Acute lymphoblastic leukemia (ALL) is the most common form of childhood cancer and a major cause of death in children. Although ALL is usually responsive to chemotherapy, about 25% of children and 65% of adults with ALL develop a relapse of their disease. The majority of these patients will die of leukemia. New approaches to the treatment of ALL are necessary to obtain cures for these patients. We have identified stromal-derived factor (SDF)-1 as a major regulator of ALL cell growth and survival ....Acute lymphoblastic leukemia (ALL) is the most common form of childhood cancer and a major cause of death in children. Although ALL is usually responsive to chemotherapy, about 25% of children and 65% of adults with ALL develop a relapse of their disease. The majority of these patients will die of leukemia. New approaches to the treatment of ALL are necessary to obtain cures for these patients. We have identified stromal-derived factor (SDF)-1 as a major regulator of ALL cell growth and survival. It is currently the only known factor that significantly stimulates the growth-survival of cells from the majority of patients with ALL. Specific antagonists of the SDF-1 receptor, CXCR4, are available. Depriving ALL cells of SDF-1 by the use of these antagonists provides a radically new approach for the treatment of ALL. CXCR4 antagonists also increase the susceptibility of ALL cells to cytotoxic drugs. The mechanisms by which SDF-1 promotes ALL cell growth and survival are not known but appear to be largely due to synergistic interactions with other molecules that have little or no effect on their own. Knowledge of the underlying mechanisms of action of SDF-1 and the factors with which it synergises will facilitate for the further development of this approach. This project will examine the modulation of the expression of proteins that regulate ALL cell growth and survival by CXCR4 antagonists, providing insights into how CXCR4 antagonists work. This project will also extend our encouraging data obtained using tissue culture to an animal model of leukemia. The antagonists will be tested in isolation and in combination with currently used chemotherapy agents. It is expected that CXCR4 antagonists will inhibit the growth of ALL cells and increase their sensitivity to chemotherapy agents in the animal model as we have seen in laboratory culture. The addition of CXCR4 antagonists to current treatment protocols is expected to significantly improve the outcome for patients.Read moreRead less