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The Australasian Leukaemia And Lymphoma Group (ALLG) Trial Centre
Funder
National Health and Medical Research Council
Funding Amount
$790,000.00
Summary
Lymphoma, leukaemia and related cancers of the blood affect thousands of Australians, including children. The Australasian Leukaemia and Lymphoma Group, a network of clinical and laboratory haematologists, will integrate laboratory research to discover new approaches to treatment, with clinical trials to test the safety and effectiveness of the new treatments. This approach should accelerate the research and maximise patient and community benefits.
We are studying stem cells and their utility for transplantation into several organ systems including blood, neural and liver. We are also determining the relevance of epigenetic changes in transplanted cells that may interfere with normal function and could be the basis for disease.
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.
The Clinical Value Of Serology And Molecular Tests For Diagnosing Invasive Aspergillosis In At-risk Hematology Patients
Funder
National Health and Medical Research Council
Funding Amount
$1,095,500.00
Summary
Aspergillus is a fungus found in soil, on farms and on construction sites. In those whose immune system is impaired it causes severe infection. The people who are particularly at high-risk of Aspergillus infection (called Invasive Aspergillosis) are those with acute leukaemia on chemotherapy or post bone marrow transplantation. Currently 15% of those at high-risk get Invasive Aspergillosis and 58-93% of those infected die. The main reason for this high death rate is that our current diagnostic t ....Aspergillus is a fungus found in soil, on farms and on construction sites. In those whose immune system is impaired it causes severe infection. The people who are particularly at high-risk of Aspergillus infection (called Invasive Aspergillosis) are those with acute leukaemia on chemotherapy or post bone marrow transplantation. Currently 15% of those at high-risk get Invasive Aspergillosis and 58-93% of those infected die. The main reason for this high death rate is that our current diagnostic tests are not good at detecting infection or often only detect the infection at advanced stages when treatment is ineffective. Because of the limitations of current diagnostic tests the current practice is to give empiric antifungal therapy (EAFT) early to treat Invasive Aspergillosis. However studies have demonstrated that this therapy has only resulted in a minor reduction in the mortality rates and it causes significant drug toxicity. It is a suboptimal treatment modality. New tests have been developed to diagnose Invasive Aspergillosis. These tests are for the detection of an Aspergillus protein in blood and for the detection of Aspergillus DNA in the blood. Available data suggests that these new tests are sensitive in the detection of Invasive Aspergillosis. Also other studies suggest that these new tests make an early diagnosis and seem to be able to monitor responses to treatment. However no study has been performed to date which demonstrates that the use of these tests can impact on important patient outcomes. This trial is designed to determine whether the use of the new tests to guide therapy will help improve treatment of Invasive Aspergillosis, reduce drug toxicity and reduce the death rate in the high-risk patients as compared with the current standard method of diagnosis and treatment with EAFT. If the trial is successful then this represents a significant advancement in the treatment and survival of leukaemic and bone marrow transplantation patients.Read moreRead less
Approaches To Allogeneic Chimerism For The Induction Of Transplantation Tolerance
Funder
National Health and Medical Research Council
Funding Amount
$212,036.00
Summary
All patients with organ failure who receive a transplant require lifelong immunosuppressive medications to prevent the body from rejecting the foreign tissue. Indefinite immunosuppressive therapy is associated with significant side-effects which include infections and cancers. In addition, long-term loss of the transplants due to slow rejection (chronic rejection) remains high. Achieving a state of immunological tolerance in which transplanted tissue is regarded as self, but reactivity to all ot ....All patients with organ failure who receive a transplant require lifelong immunosuppressive medications to prevent the body from rejecting the foreign tissue. Indefinite immunosuppressive therapy is associated with significant side-effects which include infections and cancers. In addition, long-term loss of the transplants due to slow rejection (chronic rejection) remains high. Achieving a state of immunological tolerance in which transplanted tissue is regarded as self, but reactivity to all other foreign tissues (e.g. harmful viruses, bacteria) remain normal, would solve all these problems. Tolerance would eliminate the need for immunosuppressive medications and prevent rejection of transplanted organs. The production of mixed bone marrow chimerism is a potent method of inducing tolerance. Chimerism is a state in which bone marrow tissue from two genetically different individuals coexists in one person. This can be achieved by bone marrow transplantation from a specific donor, and if chimerism is achieved, the recipient will accept all tissues from the bone marrow donor without the need for ongoing immunosuppressive therapy. This study will attempt to examine the use of different therapeutic reagents (e.g. antibodies alone or antibodies linked to idarubicin, a drug which prevent cells dividing) to develop safe protocols for the production of bone marrow chimerism and tolerance for routine clinical use in humans. The study will also examine different cellular components of the donor bone marrow which may induce tolerance.Read moreRead less
Cell Cycle Regulation, Haemopoietic Stem Cells And Myeloproliferation.
Funder
National Health and Medical Research Council
Funding Amount
$579,138.00
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.
The Molecular Mechanisms Controlling Maintenance Of Osteogenic Precursor Cells And Skeletal Tissue Regeneration
Funder
National Health and Medical Research Council
Funding Amount
$234,750.00
Summary
Within human bone marrow there exists a rare population of bone marrow stromal stem cells (BMSSCs) able to develop into the different cell types that form haematopoietic supportive stroma and surrounding skeletal tissue. There has been alot of interest of late in the potential of BMSSCs as a cellular based therapy to treat and manage bone fractures or bone loss caused by disease. Increasing evidence suggests that decreased bone mass due to osteoporosis dos not purely result in an increase of bon ....Within human bone marrow there exists a rare population of bone marrow stromal stem cells (BMSSCs) able to develop into the different cell types that form haematopoietic supportive stroma and surrounding skeletal tissue. There has been alot of interest of late in the potential of BMSSCs as a cellular based therapy to treat and manage bone fractures or bone loss caused by disease. Increasing evidence suggests that decreased bone mass due to osteoporosis dos not purely result in an increase of bone resorption by osteoclasts, but may also occur through a decline in the number of bone forming cells called osteoblasts or their progenitors. Fracture non-union, prosthetic loosening and the replacement of large defects in bone are common and difficult problems. The use of autologous bone cells generated from isolated BMSSCs in combination with bio-compatible implant materials would provide a novel solution for the treatment of these problems, avoiding the use of autografts and allografts of bone with all their associated difficulties. However, large numbers of ex vivo expanded BMSSCs are currently required to heal even small bone defects in animal models. This is compounded by the decline in proliferation rates and bone forming capacity of BMSSCs during prolonged expansion in culture. An improved understanding of the genes that regulate the proliferation and differentiation of BMSSCs in vitro is therefore an essential prerequisite for the effective management of bone fracture and bone loss. We propose to genetically manipulate the expression of genes in BMSSCs, that are known to regulate cellular growth and development inorder to maintain the growth of stem cell populations in vitro and to extend their capacity to form bone when transplanted in vivo.Read moreRead less
Where It All Begins- Exploring Dendritic Cell Control Of Viral Infection And Cell Development In The Bone Marrow Of Mice And Man.
Funder
National Health and Medical Research Council
Funding Amount
$96,335.00
Summary
The bone marrow (bm) is the birthplace of all blood cells that fight infection in the body. Dendritic cells (DC), essential for starting immune responses, are found in the bm but the exact types and their functions are unknown. I plan to investigate the DC types that reside in the bm and explore their role in inducing immune responses and in influencing the development of cells from the bm with potential attributable benefits for stem cell transplant and vaccine design.
Activated Dendritic Cell Monoclonal Antibodies As Therapeutics To Prevent Graft Versus Host Disease
Funder
National Health and Medical Research Council
Funding Amount
$432,750.00
Summary
A New Therapy to Prevent Graft versus Host Disease in Bone Marrow Transplantation Bone marrow transplants often fail due to the immune reaction of the grafted donor cells against the patient (graft versus host disease). Current treatments to prevent this do not always work and have serious side-effects or other disadvantages.The immune reaction is induced by activated dendritic cells which are the primary stimulators of the body's defences against foreign invaders. We have developed antibodies i ....A New Therapy to Prevent Graft versus Host Disease in Bone Marrow Transplantation Bone marrow transplants often fail due to the immune reaction of the grafted donor cells against the patient (graft versus host disease). Current treatments to prevent this do not always work and have serious side-effects or other disadvantages.The immune reaction is induced by activated dendritic cells which are the primary stimulators of the body's defences against foreign invaders. We have developed antibodies in mice that react with human activated dendritic cells and prevent them from inducing immune responses in the test-tube. These antibodies are also likely to be effective in patients, but cannot be used in their present form because mouse antibodies induce an undesirable immune response in humans. We therefore plan to convert them to resemble human antibodies (antibody engineering). Antibodies that react with other types of cell in the body are already used to treat or prevent a variety of conditions, including graft versus host disease, but no one has developed a therapeutic antibody against activated dendritic cells. We are applying to the NHMRC for funding to engineer our antibodies and to test them in test tube experiments and also in mouse models of graft versus host disease. We also plan to study the changes in blood levels of activated dendritic cells in bone marrow transplnt patients. This will provide information on the best time to use our new therapeutic antibodies to prevent graft versus host disease. The aim of this grant application will have been achieved if, after three years, we have a new antibody ready for testing in bone marrow transplant patients.Read moreRead less