Regulation Of Normal And Malignant Haematopoiesis By The Bone Marrow Environment
Funder
National Health and Medical Research Council
Funding Amount
$621,458.00
Summary
This project will identify factors within the bone marrow that regulate blood and immune cell formation. These include oxygenation and novel proteins identified in the applicant’s laboratory. How these factors from the bone marrow influence the behaviour of normal blood forming cells (called haematopoietic stem cells), and the progression of leukaemia and the response of leukaemia to chemotherapy treatments will be investigated. New drugs that interfere with these new factors will be tested for ....This project will identify factors within the bone marrow that regulate blood and immune cell formation. These include oxygenation and novel proteins identified in the applicant’s laboratory. How these factors from the bone marrow influence the behaviour of normal blood forming cells (called haematopoietic stem cells), and the progression of leukaemia and the response of leukaemia to chemotherapy treatments will be investigated. New drugs that interfere with these new factors will be tested for their potential to treat leukaemia.Read moreRead less
Do Bone Marrow Macrophages Regulate Leukaemia Stem Cells And Their Response To Treatment?
Funder
National Health and Medical Research Council
Funding Amount
$590,103.00
Summary
This project will investigate the role of population of immune cells called macrophages in promoting resistance of leukaemia cells to chemotherapy treatments. As a high proportion of adult patients with acute leukaemia cannot be cured with current treatments, this project could lead to more efficacious therapies targeting macrophages to sensitise leukaemia cells to chemotherapy treatments.
Recipient Bone Marrow Macrophages Contribute To Haematopoietic Stem Cell Transplantation Success
Funder
National Health and Medical Research Council
Funding Amount
$608,906.00
Summary
We propose an innovative approach to reduce risk and increase success of blood stem cell transplantation. We will determine whether a specialized cell within the transplant patient is required for donor stem cells to successfully take up residence and recreate the blood and immune system. We will test whether fortifying these specialized cells will improve transplantation outcomes, consequently increasing the number of transplants that can proceed and reducing potentially fatal complications.
Stem Cell Niches: Biology And Therapeutic Applications
Funder
National Health and Medical Research Council
Funding Amount
$640,210.00
Summary
This research aims to identify how stem cells are regulated in the body in order to improve therapies for blood disorders and abnormal bone formation after severe traumas. Targeting molecules that deregulate stem cells will lead to improved treatments for diseases with outcomes including improved treatments for blood stem cell transplantation, improved therapy in cancer patients and reduced complications of spinal cord injuries.
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.
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.
The Roles Of Retinoids And Their Receptors In Haemopoiesis
Funder
National Health and Medical Research Council
Funding Amount
$474,750.00
Summary
Haemopoietic stem cells (HSCs) are the most widely studied adult somatic stem cell. HSCs have huge potential, sustaining blood cell production throughout an individual's life. Cancers (leukaemias) and other disorders of the blood are largely treated by transplantation of HSCs. However, due to their rare occurrence, it is often difficult to obtain large numbers of HSCs for transplantation, especially from sources of HSCs such as cord blood. Furthermore, protocols requiring manipulation of HSCs, s ....Haemopoietic stem cells (HSCs) are the most widely studied adult somatic stem cell. HSCs have huge potential, sustaining blood cell production throughout an individual's life. Cancers (leukaemias) and other disorders of the blood are largely treated by transplantation of HSCs. However, due to their rare occurrence, it is often difficult to obtain large numbers of HSCs for transplantation, especially from sources of HSCs such as cord blood. Furthermore, protocols requiring manipulation of HSCs, such as gene therapy, have been largely unsuccessful, in part due to the lack of success in growing HSCs outside of the body. In such situations, therefore, determining culture conditions that would enable us to grow HSCs outside of the body are highly desirable. This application is based on the studies of CIA, who recently made the novel discoveries that the vitamin A derivative, all-trans retinoic acid (ATRA) has different effects in the regulation of blood cell production. ATRA is currently used in the treatment of acute promyelocytic leukaemia, as it enhances the maturation of the leukaemic cells. CIA has demonstrated that ATRA has the opposite effect on HSCs, with recent data strongly suggesting that ATRA induces the expansion of HSCs outside of the body. The studies outlined in this proposal seek to further define the mechanisms involved in these effects of ATRA and other vitamin A derivatives (collectively termed retinoids) in the regulation of blood cell production. The first specific aim will determine how retinoids expand HSCs. The second specific aim will explore the roles of the different RARs in the regulation of blood cell production. These studies have direct clinical relevance in improving protocols for transplantation and gene therapy of HSCs. Furthermore, insight gained into the roles of retinoids in blood cell production may also lead to the improvement of treatments of various types of blood disorders.Read moreRead less