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.
Improving Patient Outcomes In Leukaemia By Targeting Cancer Stem Cells
Funder
National Health and Medical Research Council
Funding Amount
$294,763.00
Summary
Blood cancers such as acute myeloid leukaemia (AML) are among the most deadly types of cancer and new treatments are desperately needed to improve patient’s survival in these diseases. AML cancer-causing stem cells survive by turning on immortalization programs and we hope to specifically kill these AML stem cells by blocking these crucial pathways. This includes things that control the way the cells divide and the way they respond to genetic damage as well as other novel pathways.
Understanding Autophagy In Haematopoiesis And Leukaemia
Funder
National Health and Medical Research Council
Funding Amount
$500,813.00
Summary
Blood cancers such as leukaemia are among the most deadly types of cancer and new treatments are desperately needed to improve survival. We have identified a new pathway that is activated when cells undergo stress. This pathway controls the survival of normal blood cells and also appears to be very important in the way cancer cells respond to chemotherapy. We will characterize this pathway in normal blood cells and use this information to develop new treatments to target and eliminate the leukae ....Blood cancers such as leukaemia are among the most deadly types of cancer and new treatments are desperately needed to improve survival. We have identified a new pathway that is activated when cells undergo stress. This pathway controls the survival of normal blood cells and also appears to be very important in the way cancer cells respond to chemotherapy. We will characterize this pathway in normal blood cells and use this information to develop new treatments to target and eliminate the leukaemia cells.Read moreRead less
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.
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 Evolution Of Acute Myeloid Leukaemia By In Situ Transformation Of Haematopoietic Stem Cells
Funder
National Health and Medical Research Council
Funding Amount
$646,966.00
Summary
Acute myeloid leukaemia (AML) is a devastating form of blood cancer that can affect people of any age. The survival of patients with AML is poor and this is because the disease usually comes back after chemotherapy (this is called relapse). Fewer than half of all patients with AML can be cured. We have recently developed a new, and improved, model of AML in the lab, which we will use to test an exciting new treatment for patients with AML.
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.
Genetic Fate Mapping Of Mesenchymal Stem Cell Origins And Investigating Their Contribution To Developmental Haematopoiesis
Funder
National Health and Medical Research Council
Funding Amount
$611,525.00
Summary
Mesenchymal stem cells are a population of cells that reside in various organs in the body and are thought to contribute to tissue repair. However little is known about the developmental origins and identity of these cells. I will investigate where these cells originate from, their molecular identity and how they relate to blood development. These findings will help in developing protocols to manipulate these cells to repair damaged organs. This study will also inform current attempts to generat ....Mesenchymal stem cells are a population of cells that reside in various organs in the body and are thought to contribute to tissue repair. However little is known about the developmental origins and identity of these cells. I will investigate where these cells originate from, their molecular identity and how they relate to blood development. These findings will help in developing protocols to manipulate these cells to repair damaged organs. This study will also inform current attempts to generate blood stem cells.Read moreRead less
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.