MicroRNAs are small molecules that modulate the expression of most genes and so affect nearly every biological process and pathology although, they were only discovered in humans less than 10 years ago. The bottleneck in discovering the functions of miRNAs is in identifying their molecular targets, the majority of which remain unknown. We aim to comprehensively identify direct target genes of epithelial-specific microRNAs and to confirm a number of them by gene target validation approaches.
This work will analyse how cells, the building blocks of tissues, are organized together to form functioning organs. It focuses on the adhesion molecules that allow cells to recognize one another, which cooperate with the internal skeleton of cells to link them together. We aim to understand how these cellular systems work normally and how they are targeted to disrupt tissue integrity in diseases like cancer and inflammation.
Aberrant Mesenchymal-epithelial Transition: A Pathogenic Mechanism In Tissue Maintenance And Differentiation
Funder
National Health and Medical Research Council
Funding Amount
$522,299.00
Summary
The causative genetic factors associated with aberrant changes of cellular properties are identified by analysing the profile and the control mechanism of gene expression. Specifically,this project will reveal how the transition of different patterns of tissue organization may be manifested in birth defects and malignant diseases.
Role Of The MiR-200 Target Quaking In Alternative Splicing During EMT And Cancer Progression
Funder
National Health and Medical Research Council
Funding Amount
$443,160.00
Summary
The spread of cancer to other organs involves cancer cells changing to a more aggressive state and is a major cause of cancer related death. MicroRNAs are a class of genes that control whether cancer cells become more aggressive by regulating other genes. In this project we will examine the function of a new microRNA target which controls the cancer cell aggression. The outcome will be a better understanding of how cancers spread and the identification of new therapeutic targets.
Preventing Kidney Fibrosis By Targeting Matrix Metalloproteinase-9 In Chronic Kidney Disease
Funder
National Health and Medical Research Council
Funding Amount
$516,972.00
Summary
More than 2300 Australians commence kidney replacement therapy each year and many more die of kidney failure or its complications. Kidney fibrosis is the final pathway of damage in all chronic kidney diseases. Our data demonstrates that a matrix enzyme MMP-9 is likely to be an important cause of kidney fibrosis. We aim to investigate mechanisms by which MMP-9 causes kidney fibrosis, and develop strategies involving inhibition of MMP-9 to prevent kidney fibrosis.
REVERSING EPITHELIAL TO MESENCHYMAL TRANSITION BY TARGETED EPIGENETIC EDITING IN BREAST CANCER
Funder
National Health and Medical Research Council
Funding Amount
$1,352,322.00
Summary
Cancer cell spread around the body involves changes in the cells which allow them to migrate into blood vessels, travel and then invade other organs, a process called epithelial mesenchymal transition (EMT). EMT also makes cells less sensitive to our best treatments. EMT involves switching on genes that activate these changes and switching off genes that silence them. We will develop therapy that will reverse this process, both reducing cancer spread and making cancer treatment more effective.
Targeting MicroRNA-driven Mesenchymal To Epithelial Transition To Suppress Prostate Cancer Metastasis
Funder
National Health and Medical Research Council
Funding Amount
$741,831.00
Summary
Prostate cancer kills ~3,000 men per year in Australia. The development of metastasis is the major cause of prostate cancer-associated death and has limited treatment options. In this study, we will characterise the role of a group of molecules, termed microRNAs, in prostate cancer metastasis. We will also test whether targeting microRNAs using novel drugs termed antagomiRs is an effective strategy to inhibit metastasis and thereby improve prostate cancer mortality.
Idiopathic pulmonary fibrosis (IPF) is a fatal disease of unknown cause which is unresponsive to current therapy. This study builds on recent work by this group highlighting the importance of a cell signalling molecule called STAT3 in the development of this disease. In particular, two cell types that utilise STAT3 signalling, epithelial cells and B cells, will be examined to see if blocking their STAT3 responses could be a novel therapeutic approach.
Genetic Programs Orchestrated By AP-1 Transcription Factors In Colorectal Cancer Progression
Funder
National Health and Medical Research Council
Funding Amount
$599,941.00
Summary
Colorectal cancer (CRC) is the third most common cancer worldwide. About half of all patients diagnosed with the disease die as a result of its spread in the body. This project will investigate the role that a specific DNA-binding protein plays in orchestrating gene expression programs required for CRCs to spread. The research will provide new insights into underlying mechanisms of CRC progression as well as identify new therapeutic targets for aggressive forms of the disease.
Identification Of PACE-1 As A Novel Therapeutic Target For The Treatment Of Prostate Cancer
Funder
National Health and Medical Research Council
Funding Amount
$606,144.00
Summary
Advanced prostate cancer (PCa) remains the major therapeutic challenge since neither surgery nor systemic therapies are effective at this stage. Recently, we identified a protein called PACE-1 that is essential for PCa cell survival. We plan to investigate the roles of PACE-1 in the development and progression of prostate cancer. We will then test if PACE-1 inactivation alone or in combination with systemic cancer therapies will inhibit prostate tumor growth and disease progression.