Myelodysplastic Syndrome And The Bone Marrow Microenvironment
Funder
National Health and Medical Research Council
Funding Amount
$562,654.00
Summary
We are interested in how myelodysplastic syndrome (MDS) affects the function of the bone marrow. We believe that changes associated with anaemia of MDS cause the bone marrow to be altered. This proposal addresses this question and explores new treatment approaches
Targeting Tumour Angiogenesis In Breast Cancer By Altering MicroRNA Signalling
Funder
National Health and Medical Research Council
Funding Amount
$660,151.00
Summary
Despite advances in treatment, breast cancer remains one of the leading underlying causes of death and disability in Australia. Preventing cancer spread therefore has the potential for enormous economic and social outcomes. Small RNAs have recently been identified as key regulators of cancer cell biology. This project seeks to take a leadership role in the area of small RNA biology by targeting small RNAs implicated in blood vessel formation as a means of suppressing breast cancer spread.
Piezo2 And Pain - Is There A Role For Piezo2 In Mechanically Induced Bone Pain?
Funder
National Health and Medical Research Council
Funding Amount
$543,848.00
Summary
Pain associated with bone marrow edema, osteoarthritis, bone cancer and fracture puts a significant burden on individuals, society, and the health care system in Australia. A dominant feature of these includes mechanical disturbances of the bone, and this is a trigger for the pain. In this study, we will determine if a newly discovered mechanically gated ion channel (Piezo2) is a key contributor to mechanically induced bone pain and could be a target for development of drugs to treat it.
Bone Marrow Macrophages: “Resident Evil” In The Establishment And Progression Of Multiple Myeloma
Funder
National Health and Medical Research Council
Funding Amount
$570,585.00
Summary
Multiple myeloma (MM) is a cancer that develops within the bone marrow (BM). To date, which cells of the BM stroma are required for the support of MM growth remains unknown. Our preliminary data suggest BM resident macrophages, expressing CD169 and CX3CR1, are essential for MM growth. Using innovative and elegant animal models of MM, we will define the role of these macrophages in MM growth and determine if macrophage-targeted therapies can delay MM growth in the relapsed disease setting.
Reconstitution Of B-cell Ontogeny In Btk-deficient Patient-derived CD34+ Cells In A Humanised Mouse Model: The Foundations For An Australian XLA Gene Therapy Trial
Funder
National Health and Medical Research Council
Funding Amount
$678,652.00
Summary
Gene therapy targeting the bone marrow has broad therapeutic potential in the management of genetic diseases, viral infections and cancers involving blood cells. In this proposal we plan to obtain bone marrow cells from patients with X-linked agammaglobulinaemia and show that their cells can be genetically repaired in the test tube and, when transferred back into a specialised mouse models, reconstitute the immune system. The results have the potential to underpin a human clinical trial.
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.
Why Is The Bone Marrow A “hot-spot” For Myeloma Plasma Cell Metastasis: Are There Gremlins In The System?
Funder
National Health and Medical Research Council
Funding Amount
$651,979.00
Summary
Most cancer patients die because their cancer spreads from a primary site to other tissues in the body. Once escaping the primary site, 70% of all tumours will spread to bone. This raises the question, why is bone a preferred destination for cancer cells? We provide evidence that Gremlin1, made by non-cancer cells within bone, is a key protein that supports cancer growth. This study will examine whether inhibiting Gremlin1 is a potential therapy to inhibit cancer spreading to bone.
Increasing Haematopoietic Stem Cell Mobilisation By Targeting A Novel Niche Factor
Funder
National Health and Medical Research Council
Funding Amount
$707,218.00
Summary
Transplantation of patients’ own blood stem cells is used to treat many blood cancers. It increases the chance of cure. However the damage caused by chemotherapies used to combat the cancer can compromise stem cell collection and transplantation. Without transplant, these patients are less likely to be cured. This project is to test new drugs that enhance the harvest of blood stem cells for transplantation. These will increase the success rates of transplants and cure in these cancer patients.
Effective Therapies To Treat Viral Infections And Their Complications In Transplantation
Funder
National Health and Medical Research Council
Funding Amount
$1,100,450.00
Summary
Viral infections are a common life threatening complication in transplant recipients, for which there are limited treatment options. We have developed several pre-clinical models that we are using to determine how the treatment of viral infections that occur after transplantation can be improved.
Developing Bone Marrow Transplant And Novel Therapeutic Vectors To Treat Friedreich Ataxia
Funder
National Health and Medical Research Council
Funding Amount
$598,163.00
Summary
We aim to develop effective therapies for the neuromuscular disease Friedreich ataxia (FRDA). The neurodegeneration inherent to FRDA slowly robs a person of the ability to move freely and care for themselves. It needs life-long medical support and there is no cure. FRDA lowers frataxin, a critical mitochondrial protein. Evidence indicates increasing frataxin can be beneficial. Using disease models, we will determine if increasing frataxin via bone marrow transplant or gene therapy improves FRDA.