Antigen Receptor As Oncogene: Understanding CARD11 Mutations In B Cell Malignancy
Funder
National Health and Medical Research Council
Funding Amount
$607,395.00
Summary
More than 5000 Australians are newly diagnosed as lymphomas. Recent technology identified many candidate genes for lymphomas, however it still remains unclear how each mutated gene distorts signalling molecules inside tumours cells. By introducing one of recurrent mutated genes, CARD11 into mouse B cells, we will examine how this mutation affects normal signalling pathways and B cell functions. We hope this project will provide a guidance to use forthcoming drugs to target specific molecules.
Therapeutic Targeting Of MYCN Oncoprotein Stability In Neuroblastoma
Funder
National Health and Medical Research Council
Funding Amount
$590,206.00
Summary
A high level of MYCN protein is a major indicator of aggressive neuroblastoma (NB) but unfortunately there have been many barriers to the design of targeted therapies. We have identified a protein called PA2G4 which is a cofactor for MYCN in promoting cancer cell growth. We have developed a compound which inhibits PA2G4 and MYCN protein levels and reduces tumour growth. We will examine how PA2G4 cause aggressive tumour characteristics and test new methods to block PA2G4.
A Novel Molecular Target Capable Of Abrogating Neuroblastoma Development
Funder
National Health and Medical Research Council
Funding Amount
$802,499.00
Summary
Although modern chemotherapy has significantly improved survival rates for many childhood cancers, the outlook remains dismal for children with advanced staged neuroblastoma. These patients frequently have alterations in the cancer-causing gene called MYCN. Using pre-clinical models of MYCN-driven neuroblastoma and genome sequencing we have discovered a gene that can completely block the action of MYCN and prevent neuroblastoma growth. This work will characterize the function of this novel gene.
Targeting The Oncoprotein MDMX As A Novel Treatment For Triple Negative Breast Cancer
Funder
National Health and Medical Research Council
Funding Amount
$561,672.00
Summary
Breast cancer (BrCa) is a leading cause of cancer death in women worldwide. BrCas unable to respond to current therapies have the worst outcomes. We propose a novel strategy to treat these cancers, based on our new findings. Our two protein targets are: (1) MDMX, that we found drives BrCa with its partner, (2) mutant p53, which causes cancer spread. We plan to directly target these drivers of aggressive BrCas, using new drugs that individually show great promise in trials in a number of cance
Determinants Of Progression Of Actinic Keratoses To Squamous Cancer
Funder
National Health and Medical Research Council
Funding Amount
$1,188,498.00
Summary
Sunspots can progress to skin cancers, but often go away on their own. Knowing which ones will go away would make management of sun damaged skin easier, and might let us develop new treatments. This grant will examine why some sunspots progress and others don't.
Consequences Of MYD88 Mutations Commonly Found In Human B Cell Malignancies
Funder
National Health and Medical Research Council
Funding Amount
$442,583.00
Summary
MYD88 is one of the most recurrently mutated genes in B cell malignancies, such as diffuse-large B cell lymphoma and Waldenström macroglobulinemia. This project will characterise oncogenic MYD88 mutations by introducing the mutations into normal mouse B cells. It will examine how the mutations disrupt signalling pathways and B cell functions and how the mutations respond to new lymphoma drugs. We hope this project will provide information for lymphoma pathogenesis and rational drug selection.
Impact Of Aberrant Branchpoint Selection In Myelodysplasia And Chronic Lymphocytic Leukaemia.
Funder
National Health and Medical Research Council
Funding Amount
$605,326.00
Summary
Most human genes are spliced together from smaller exon parts. CIA Mercer has found that if splicing proceeds incorrectly backwards, small circular RNAs and incomplete genes are built. The splicing machinery responsible for this process is recurrently mutated in blood disorders, notably Myelodysplasia and Chronic Lymphocytic Leukaemia. We propose that these mutations cause backwards splicing of key genes responsible for these disorders, representing a major new pathway to cancer.
Cell survival and death are controlled by two processes known as apoptosis and autophagy. Apoptosis eliminates damaged cells whereas autophagy gets rid of faulty components in the cell. The Bcl-2 proteins regulate both processes. It is well established that dysfunctional Bcl-2 regulation leads to cancer. In this project, we aim to investigate if deregulated Bcl-2 control of autophagy also has a key role in cancer progression and to obtain a molecular picture of how this control is exerted.