Overcoming Breast Cancer Heterogeneity And Resistance Using A Novel Therapeutic Approach Targeting The Metastasis Suppressor NDRG1.
Funder
National Health and Medical Research Council
Funding Amount
$431,000.00
Summary
Breast cancer (BrCa) is the leading cause of cancer death in women and current treatments suffer from development of resistance, leading to metastatic progression. I will assess a novel treatment strategy for BrCa, targeting a gene that is able to inhibit multiple key drivers of BrCa, using a novel potent and selective anti-cancer agent. This approach has the potential to overcome resistance to current therapies and alleviate the onset of metastasis, to improve prognosis for BrCa patients.
Acceptance And Commitment Therapy For Medication-resistant Psychosis: A Randomised Controlled Trial
Funder
National Health and Medical Research Council
Funding Amount
$558,200.00
Summary
In spite of advances in medication, approximately one third of people with schizophrenia continue to experience distressing symptoms such as hearing voices and paranoia. Psychological 'talking treatments' are effective in helping people to cope with and be less distressed by these experiences. This study will be the first trial of a new psychological treatment, called Acceptance and Commitment Therapy, which may be more effective, briefer and more easily provided than existing approaches.
TACI: A Novel Immune Checkpoint In Chronic Lymphocytic Leukemia
Funder
National Health and Medical Research Council
Funding Amount
$874,462.00
Summary
Chronic Lymphocytic Leukemia (CLL) is a very common blood cancer. CLL cells actively shut down immune defenses in patients. Moreover, current as well as emerging more targeted therapies suppress immunity and over a quarter of patients will die from an infection despite a good response to cancer treatments. Our laboratory has gained new understanding in the mechanism of action of a new treatment for CLL called Ibrutinib. This information allows us to design improved treatment options for CLL.
The Developmental Hierarchy Of Haemopoietic Lineage Relationships
Funder
National Health and Medical Research Council
Funding Amount
$192,000.00
Summary
The blood cells are all the progeny of a very rare stem cell, that is thought to reside in the bone marrow. The stem cell maintains itself throughout the life span of the individual as well as generating the billions of more mature cell types required in the blood. However the processes and stages that immature cells pass through from the stem cell to ultimately a mature functional blood cell such as a lymphocyte remain disputed. This study aims to determine to relationship of the various blood ....The blood cells are all the progeny of a very rare stem cell, that is thought to reside in the bone marrow. The stem cell maintains itself throughout the life span of the individual as well as generating the billions of more mature cell types required in the blood. However the processes and stages that immature cells pass through from the stem cell to ultimately a mature functional blood cell such as a lymphocyte remain disputed. This study aims to determine to relationship of the various blood cell progeny with each other and thus to provide a lineage map of the system. To do this we will isolate precursors at various stages along the developmental pathways and determine their capabilities to produce the normal range of progeny. We will then use a number of genetically altered mouse strains to assess the genes involved in this process. These studies will help provide an underlying scientific basis to the attempts to development a number of stem cell therapies that are aimed at boosting or directing stem cell production in procedures such as bone marrow transplantation for leukemia and immune deficiency. In addition a number of characterized human blood malignancies seem to have developed along aberrant pathways indicating that inappropriate lineage specification may be a factor in cancer.Read moreRead less
Characterization Of Haemopoietic Lineage Determining Genes
Funder
National Health and Medical Research Council
Funding Amount
$631,021.00
Summary
Haemopoiesis is the process by which blood cells develop from stem cells. This process is tightly regulated and is dependant upon the appropriate expression of genes at each developmental stage within various lineages. Our work focuses on two genes (Mlf1 and Hls5) that are involved in determining lineage commitment and affect the expression of key hemopoietic regulators. If these genes are aberrantly expressed leukemias and other blood disorders can develop.
Characterisation Of Novel Regulators Of The Haemopoeitic System.
Funder
National Health and Medical Research Council
Funding Amount
$381,680.00
Summary
All of the circulating blood cells (including red cells and white cells) develop from a single cell type, called the haemopoietic stem cell (HSC), found in the adult bone marrow. Normally, HSCs are gradually restricted to become only one cell type and once they have started down that pathway can no longer generate cells of another pathway (e.g. once HSC begin to develop into red blood cells, they cannot normally change their direction to become white cells). There are a few examples of mature ce ....All of the circulating blood cells (including red cells and white cells) develop from a single cell type, called the haemopoietic stem cell (HSC), found in the adult bone marrow. Normally, HSCs are gradually restricted to become only one cell type and once they have started down that pathway can no longer generate cells of another pathway (e.g. once HSC begin to develop into red blood cells, they cannot normally change their direction to become white cells). There are a few examples of mature cells, however, that have changed pathways. We have use one of these, the mouse J2E red cell changing into macrophages, to identify the genes involved in this process. Two of the genes we found, HLS5 and HLS7, are potentially important in lineage determination and normal blood development as well as the formation of blood cancers. This project aims to investigate the roles these genes play in blood development. Much of our work to date has focused on HLS7. The human equivalent of HLS7 was found by an American group independently of us as a gene which causes one type of blood cancer. We have shown HLS7 has dramatic effects on normal blood development and, together, these results clearly show the importance of this gene. Through our studies on how HLS7 works, we have identified another gene, M44, which may be important in regulation of HLS7 and also plan to investigate is function. Finally, HLS5 has similarities to a group of molecules called transcription factors which are known to be key regulators blood development. Clearly, analysis of this gene will further our knowledge in this field.Read moreRead less