Cancer arises through a combination of common DNA mutations which are associated with very poor survival in certain cancers. However, the cause of these mutations was always believed to be external factors (eg. UV light, toxins), Our exciting preliminary results show internal molecules, called circular RNAs, can drive these mutations and this project will investigate how this occurs and study whether targeting these molecules can reduce the incidence of cancers.
The Role Of Oncogenes, Cell Death Machinery And Novel Players In The Regulation Of Hematopoietic Stem Cells, Leukemogenesis And Hematological Disorders
Funder
National Health and Medical Research Council
Funding Amount
$763,409.00
Summary
This project is focused on the regulation of blood cells and the diseases that arise when they become defective, such as bone marrow failure and leukemia. It will investigate how proteins involved in cell suicide impact on blood cell survival, cancer therapy, and the formation of blood clots. The link between cancer genes and stem cells will be examined. Ultimately, the aims are to identify drug targets in hematological disorders, and develop new drugs to promote the survival of healthy cells.
Screening For Recently Defined Genetic Lesions In Poor Risk Adult And Childhood ALL, And Developing Treatment Approaches To Target Causative Pathways.
Funder
National Health and Medical Research Council
Funding Amount
$744,938.00
Summary
Most adults and 20% of children with ALL relapse and die of their disease. Chromosomal changes resulting in the formation of new proteins have been recently identified in a significant number of cases. Importantly, drugs targeting these proteins are in clinical practice for other diseases. We will develop new tests to rapidly identify these patients at diagnosis, and assess the efficacy of adding these drugs to first line treatment in a clinical trial. The outcome for these patients will likely ....Most adults and 20% of children with ALL relapse and die of their disease. Chromosomal changes resulting in the formation of new proteins have been recently identified in a significant number of cases. Importantly, drugs targeting these proteins are in clinical practice for other diseases. We will develop new tests to rapidly identify these patients at diagnosis, and assess the efficacy of adding these drugs to first line treatment in a clinical trial. The outcome for these patients will likely improve significantly using this approachRead moreRead less
The Role Of The Polarity Protein, Par3, In Haematopoiesis And Leukaemogenesis
Funder
National Health and Medical Research Council
Funding Amount
$589,777.00
Summary
Understanding the factors regulating blood production is critical to understanding how blood cancers occur and for the development of new therapies. Evidence is emerging of a vital role for the evolutionary conserved ‘polarity’ proteins in blood production and leukaemia This project will elucidate the role of the polarity protein, Par3, in normal and malignant blood cells, providing valuable insight into how Par3 regulates blood formation and the onset and severity of leukaemia.
The BHLH Transcription Factor LYL1 In Normal And Leukemic Hematopoiesis
Funder
National Health and Medical Research Council
Funding Amount
$520,945.00
Summary
This project aims to understand how two closely related genes, called SCL and LYL1, work together to control the production of normal red blood cells and when abnormally expressed, cause cancer of the white blood cells. We will specifcially examine how LYL1 causes a specific type of leukemia in children and determine blocking the function of LYL1 will be a useful way to kill leukemia cells.
Myeloproliferative diseases (MPD) and leukemias arise from blood cells with faulty molecular signalling caused by genetic mutations. We are studying MPD and leukemias that carry over-active versions of the JAK2 signalling molecule. We will use human and mouse leukemias and MPD to discover how these diseases develop, and how we can use specific medications to stop these processes. Our goal is to discover new, improved ways to treat leukemias and MPDs.
Understanding The Multistep Pathogenesis Of T-cell Leukaemia
Funder
National Health and Medical Research Council
Funding Amount
$701,992.00
Summary
Lmo2 is a transcription factor whose overexpression is a common cause of T-cell leukaemia. This project seeks to identify downstream targets of Lmo2 that cause T-cell leukemia. In addition, the origins and effects of secondary mutations that collaborate with Lmo2 in causing T-cell leukaemia will be determined. This will improve our understanding of how T-cell leukaemia develops and provide new molecular targets for therapy.
Genetic And Molecular Characterisation Of Erg Function In Normal And Malignant Haemopoiesis
Funder
National Health and Medical Research Council
Funding Amount
$647,631.00
Summary
In the human body, production of blood cells to carry oxygen, stop bleeding and fight infection is highly controlled. The transcription factor Erg is critical in delivering proper instructions so blood cells develop normally. Too much or too little Erg leads to abnormal blood cell development and blood diseases such as seen in children with Down Syndrome or patients who develop acute leukemia. The reasons why this happens will be investigated to allow for better treatment of these conditions.
The Role Of The Homeobox Transcription Factor Hhex In Haematopoiesis And Leukaemia
Funder
National Health and Medical Research Council
Funding Amount
$623,112.00
Summary
We have shown that the Haematopoietically expressed homeobox (Hhex) protein plays important roles in development of immune cells. In addition, Hhex is required for development and maintenance of Acute Myeloid Leukemia (AML). This project will further investigate the requirement of Hhex in human AML, potentially identifying a new therapeutic target in this poor-prognosis cancer subtype. In addition, we will identify critical cofactors and targets of Hhex, revealing new therapeutic strategies.