Interaction Between Moz And PRC1 In Defining Epigenetic States And Gene Expression Patterns
Funder
National Health and Medical Research Council
Funding Amount
$427,271.00
Summary
Regulation of gene expression is implicated in all disease processes. Aberrant gene expression is particularly associated with tumour formation. In this project we determine the relationship between an oncogene MOZ and another oncogene BMI1. Together these proteins regulate one of the most important systems controlling gene expression at the level of chromatin structure.
HEREDITARY ENDOCRINE CANCER: A MODEL BASED ON PHAEOCHROMOCYTOMA- PARAGANGLIOMA SYNDROMES
Funder
National Health and Medical Research Council
Funding Amount
$875,894.00
Summary
Phaeochromocytomas and paragangliomas are tumours remarkable for their very high heritability. They have a high burden of disease themselves, and their associated hereditary syndromes include risks for other malignancies. Our study will rationalize the pathological approach to diagnosing these hereditary syndromes, find new therapeutic targets for metastatic disease, and provide a template for other cancers with high heritable component.
Understanding And Targeting Acquired Chemoresistance In High-grade Serous Ovarian Cancer
Funder
National Health and Medical Research Council
Funding Amount
$527,824.00
Summary
We recently discovered a mutation in recurrent high-grade serous ovarian cancer that causes profound overexpression of the multidrug resistance pump, MDR1 (Patch et al Nature 2015). In this study I will explore approaches to reverse drug resistance caused by this mutation in recurrent ovarian cancer with a view to utilising alternative treatments to improve patient outcomes.
Genome Engineered, Preclinical Models Of Serrated Colorectal Cancer To Fast-track A High Sensitivity, Early Detection Test
Funder
National Health and Medical Research Council
Funding Amount
$593,854.00
Summary
1 in 12 Australians will develop colorectal cancer. Here we use information about changes to the genetic (inherited) material of these cancers to develop new, complex models of this disease. This teaches us about what those changes do, and highlights important targets for future drug therapies. We are also developing a better test to detect hidden pre-cancers that are not well detected by our current population screening strategy, to help reduce deaths from this disease.
Developing Cancer Therapies That Target Chromosomal Instability
Funder
National Health and Medical Research Council
Funding Amount
$644,126.00
Summary
A significant reason why late-stage cancers are hard to treat with drugs is because the tumour cells show genetic variability, always producing new variants that sooner or later get around the drugs. We intend to combat this by targeting the ability of cancer cells to vary genetically - we are discovering ways to specifically kill genetically unstable cells. This prevents the cancer from developing drug resistance as well as having less side effects on the patient's normal cells.
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.
Mab Immunotherapies For Myeloid Leukemia Patients With Germline Or Somatic RUNX1 Mutations.
Funder
National Health and Medical Research Council
Funding Amount
$766,995.00
Summary
This proposal presents preliminary evidence and proposes to confirm that 2 cell surface molecules, CD11a (ITGAL) and IL3RA (CD123) are direct (probably repression) targets of RUNX1 in HSCs, and are dysregulated in RUNX1 mutated AML. Monoclonal antibody therapies that target these two surface molecules have already passed different clinical trial phases for different diseases. We plan to show these antibodies are effective in RUNX1 positive AML in preclinical models and then clinical trials.
Role Of The LIM-only Protein LMO4 In Lung Development And Lung Cancer
Funder
National Health and Medical Research Council
Funding Amount
$490,395.00
Summary
Lung cancer is the leading cause of death in cancer patients in Australia. Although treatments have improved in the past 10 years, new therapeutic strategies are eagerly awaited. Deregulation of molecules driving development of normal tissue is often observed in cancer. Our aim is to identify key regulators of lung development and lung repair after injury. We aim to evaluate the role of these molecules in the initiation and progression of lung cancer to identify new targets for therapies.
The Role Of Centromere Defects In Cancer Formation And Progression
Funder
National Health and Medical Research Council
Funding Amount
$601,386.00
Summary
When cells divide, their DNA must be copied and distributed faultlessly into the new cells. Defects in the factors that control this process will result in serious health problems including cancer. The objective of this project is to identify what these factors are and study how they contribute to cancer. Results gained from this project are expected to significantly increase our understanding of how cancer cells control the replication of their DNA and therefore their own fate.
The Role Of Scube Gene Function In Hedgehog Signal Transduction
Funder
National Health and Medical Research Council
Funding Amount
$547,216.00
Summary
The Hedgehog signaling pathway controls development of the early embryo and is one of the most common pathways mutated in human cancer. Through the use of zebrafish genetics we have identified a new component of this pathway, Scube2 that controls the ability of cells to be activated by Hedgehog signaling. We plan to further investigate how this occurs and design therapeutically relevant peptides based on the scube2 protein that could act as inhibitors of the pathway