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
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.
Investigation Of Haematopoietic And Leukemia Stem Cell Self-renewal.
Funder
National Health and Medical Research Council
Funding Amount
$415,218.00
Summary
The blood stem cell properties of self-renewal and multipotency allows for the constant replenishment of all blood components. Blood cancer stem cells use self-renewal to propagate disease, and can enter a quiescent-dormant phase to evade treatment. My research focuses on the identification and mechanisms of new genes that govern these unique blood stem cell properties, and to investigate whether these genes are also important in blood cancers.
Determining The Transcriptional Programme Of A Leukaemogenic Transcription Factor In Normal And Leukaemic Cells
Funder
National Health and Medical Research Council
Funding Amount
$643,958.00
Summary
Leukaemic (blood cancer) cells develop from immature blood cells by inappropriate expression of genes. These genes are also those that are required for normal blood production in the embryo. Gene expression during normal blood development is tightly controlled. However in leukaemia, these genes are expressed at inappropriate stages of blood development. We will investigate whether leukaemic cells adopt features of embryonic blood stem cells to express genes that convert normal cells into abnorma ....Leukaemic (blood cancer) cells develop from immature blood cells by inappropriate expression of genes. These genes are also those that are required for normal blood production in the embryo. Gene expression during normal blood development is tightly controlled. However in leukaemia, these genes are expressed at inappropriate stages of blood development. We will investigate whether leukaemic cells adopt features of embryonic blood stem cells to express genes that convert normal cells into abnormal cells.Read moreRead less
Is Hypoxia Inducible Factor 2 The Trigger Of The Angiogenic Switch And A Driver Of Disease Progression In Myeloma?
Funder
National Health and Medical Research Council
Funding Amount
$605,096.00
Summary
Multiple myeloma (MM) is a fatal cancer of plasma cells (PC). PC migrate to the bone marrow, which compared with other organs is low in oxygen (hypoxic). In response to this hypoxia, the cancer cells turn on the expression of genes called hypoxia-inducible factors (HIF). HIFs activate the expression of genes that encourage blood vessel formation, which in turn stimulates greater tumour growth and disease progression. This proposal will investigate the role of HIFs in the progression of MM.
Klf5 Function In Normal And Leukaemic Haemopoiesis
Funder
National Health and Medical Research Council
Funding Amount
$609,924.00
Summary
Acute Myeloid Leukaemia (AML) is a devastating disease that affects both children and adults. New treatments that target particular genetic abnormalities are urgently needed. We have identified KLF5 as a gene that may control blood cell maturation. In AML patient samples we have found alterations of the KLF5 gene that may suppress its activity and contribute to the formation of leukaemia. These leukaemias may be good candidates for treatment with new drugs called methyltransferase inhibitors.
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
A-Prof Roberst is a clinical haematologist caring for patients with blood cancers, who is committed to developing new therapies for currently incurable diseases through laboratory and clinical trial research.
Molecular And Cellular Mechanisms Of Skeletal Disease Mediated By Plasma Cell Dyscrasias
Funder
National Health and Medical Research Council
Funding Amount
$432,750.00
Summary
Osteolytic and osteosclerotic lesions of bone are common sequelae of primary and secondary bone cancers, including cancers of hematological origin. There is now strong evidence that tumor cells perturb the local balance between bone resorption and formation, and in cases of osteolysis, cause increased osteoclast (OC)-mediated bone resorption without a matching amount of bone formation. This proposal arises from our extensive clinical and basic science experience with multiple myeloma (MM) in add ....Osteolytic and osteosclerotic lesions of bone are common sequelae of primary and secondary bone cancers, including cancers of hematological origin. There is now strong evidence that tumor cells perturb the local balance between bone resorption and formation, and in cases of osteolysis, cause increased osteoclast (OC)-mediated bone resorption without a matching amount of bone formation. This proposal arises from our extensive clinical and basic science experience with multiple myeloma (MM) in addition to other skeletal tumors, and our strong background in both OC and osteoblast biology. MM is a hematological malignancy characterised by plasma cell dyscrasia, which typically causes progressive and severe destruction of the skeleton, with accompanying bone pain, fracture and finally, hypercalcaemia of malignancy. Two related diseases, MGUS and POEMS, have been chosen for study because of their key similarities and differences with MM, and are likely to shed new light on the activities of MM in the bone. MGUS does not cause identifiable bone defects, whereas POEMS can give rise to both osteolytic and osteosclerotic lesions. Comparison of these conditions will uniquely enable us to examine why these seemingly related neoplasms are able to mediate disparate skeletal disease states. Primarily, and since there are few curative therapies for MM at present, our proposed studies are designed to identify targets for therapy that will treat the most serious manifestation of this disease, namely its destruction of bone tissue.Read moreRead less