A Novel Molecular Mechanism Controlling Myelopoiesis
Funder
National Health and Medical Research Council
Funding Amount
$878,439.00
Summary
The immune system is comprised of many different cell types, each with a specialised function. Many are short-lived and must be continually replenished throughout life. Abnormalities in this process underlie many human diseases, including immunodeficiency, autoimmunity and cancer. We have discovered a novel molecular mechanism that is critical for the production of immune cells. This project will investigate how this mechanism is controlled and the impacts on myelodysplastic syndromes.
Co-operation Between GATA2 Mutation Or Expression And RAS Signalling In AML
Funder
National Health and Medical Research Council
Funding Amount
$860,601.00
Summary
We have identified a gene GATA2 which, when mutated, can lead to leukaemia (blood cancer). We will collect samples worldwide from families and individuals that carry GATA2 mutations and have developed leukaemia, and will screen for other genetic changes that contribute to leukaemia. We have also identified a novel group of patients who have a low GATA2 activity and who also have mutations in the RAS gene, a known contributor to leukaemia. We will determine how these cooperate to cause leukaemia.
Identification Of Haematopoietic Stem And Progenitor Cell Subpopulations
Funder
National Health and Medical Research Council
Funding Amount
$873,525.00
Summary
We want to dissect the machinery underlying how each and every individual stem and progenitor cell generates the different blood cell types. We have at our disposal the latest molecular and computational technologies to do this. Knowledge gained from this project could be used for tissue engineering to make blood cells on demand for patients with immune deficiency, or alternatively to treat leukaemia patients where blood cells are overproduced.
Targeting The EGFR And C-Met Tyrosine Kinase Receptors In Myeloproliferative Neoplasms
Funder
National Health and Medical Research Council
Funding Amount
$607,559.00
Summary
We propose that in the blood disorders called Myeloproliferative Neoplasms (MPN) there are important changes that affect the function of receptors expressed on the surface of blood cells. These changes will perturb blood cell production and may be able to be targeted effectively with drugs. We will test this using laboratory-based and mouse models of MPN, together with specific drugs that are currently in the clinic, and that inhibit the activity of the key receptors involved. This approach can ....We propose that in the blood disorders called Myeloproliferative Neoplasms (MPN) there are important changes that affect the function of receptors expressed on the surface of blood cells. These changes will perturb blood cell production and may be able to be targeted effectively with drugs. We will test this using laboratory-based and mouse models of MPN, together with specific drugs that are currently in the clinic, and that inhibit the activity of the key receptors involved. This approach can be rapidly translated to clinical trial.Read moreRead less
Molecular Regulation Of Blood Cell Production And Function
Funder
National Health and Medical Research Council
Funding Amount
$18,330,902.00
Summary
This Program comprises an established team of investigators that have made world-class contributions to the understanding of blood cell formation and function. Research will combine novel multidisciplinary genetic/genomics approaches, expert biochemistry, cell and molecular biological techniques with translational studies in humans to provide new insights into blood cell control and novel avenues for therapies in blood cell diseases such as leukaemia and autoimmune and inflammatory disorders.
As the first recruited cells, neutrophils direct protective responses against infection, but can also mediate destructive responses in inflammatory disease. This project will determine mechanisms driving neutrophil-dependent inflammation in both settings, by examining a specific inflammation-promoting molecular pathway (the ïinflammasomeÍ) in neutrophils. This research will lead to a better understanding of inflammation, and may suggest therapeutics for treating inflammatory disease.
A Comprehensive Analysis Of Myb Target Genes Involved In Myelopoiesis And Myeloid Transformation
Funder
National Health and Medical Research Council
Funding Amount
$511,294.00
Summary
The MYB gene is essential for both normal blood cell formation and the growth of leukaemia cells. It acts by switching other genes (target genes) on and off. This project aims to advance our understanding of how MYB functions, by carrying out a comprehensive search for MYB target genes. In particular it will focus on target genes that help explain MYB's ability to control cellular growth and maturation. Some of these target genes may provide leads for future anti-cancer drug development.
Defining The Leukaemogenic Mechanism For GATA2 T354M, A New Predisposing Mutation In Familial MDS/AML
Funder
National Health and Medical Research Council
Funding Amount
$631,883.00
Summary
A successful approach for identification of cancer genes has been to study the 5-10% of cases occurring in families with inherited predisposition to develop cancer. Unlike solid tumours, few cancer-causing mutations are known for haematological cancers. We have found a new mutation in 3 families in a gene (GATA2) not previously associated with familial acute myeloid leukaemia. We will explore how this mutation causes leukaemia to help better understand the more common non-inherited leukaemias.