A Tyrosine Phosphatase That Regulates Adherens Junctions, Cell Migration And The Epithelial-mesenchymal Transition
Funder
National Health and Medical Research Council
Funding Amount
$496,500.00
Summary
Cell-cell adhesion which physically glues cells together to form tissues and organs, also controls processes in development, wound healing and cancer progression. I have identified a novel regulator of cell-cell adhesion that regulates cell migration and cell morphology. Since these events are crucial during metastasis (the spread of cancer) and during wound healing, understanding the function of this novel regulator may provide the basis for new approaches to developing therapeutics. Specifical ....Cell-cell adhesion which physically glues cells together to form tissues and organs, also controls processes in development, wound healing and cancer progression. I have identified a novel regulator of cell-cell adhesion that regulates cell migration and cell morphology. Since these events are crucial during metastasis (the spread of cancer) and during wound healing, understanding the function of this novel regulator may provide the basis for new approaches to developing therapeutics. Specifically, in this proposal I aim to further our understanding of the function of this novel regulator in normal physiology and to elucidate how its functions are regulated.Read moreRead less
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.
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.
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.
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.
Microenvironmental Regulation Of The Tissue Regenerative Capacity Of Keratinocyte Stem Cells And Their Progeny.
Funder
National Health and Medical Research Council
Funding Amount
$391,762.00
Summary
The protective outer layers of the skin known as the epidermis belongs to a group of tissues in the body that are turning over at a rapid rate. The majority ofepidermal cells have a lifespan of just 2-3 weeks, and are shed as mature cells from the skin's surface. These cells are replaced by continuous cell regeneration which is dependent on growth factors and adhesive molecules (and other signals). It has recently come to light that the connective tissue of the skin i.e. the dermis, which lies d ....The protective outer layers of the skin known as the epidermis belongs to a group of tissues in the body that are turning over at a rapid rate. The majority ofepidermal cells have a lifespan of just 2-3 weeks, and are shed as mature cells from the skin's surface. These cells are replaced by continuous cell regeneration which is dependent on growth factors and adhesive molecules (and other signals). It has recently come to light that the connective tissue of the skin i.e. the dermis, which lies directly below the epidermal cells has a critical role in providing some of these factors required for their growth and maturation. Indeed, it is becoming increasingly clear that the epidermal and dermal cells co-operate to regulate epidermal proliferation and maturation. Recent work from our laboratory has shown that a newly recognised adhesive protein laminin-10 may be produced as the result of such co-operation and that it stimulates the growth of both normal and tumour epidermal cells. We have also recently identified an interesting subset of dermal cells that may have a role in promoting the growth of the epidermal cells. Thus, the aims of the proposed stuides are to investigate the role of laminin-10 and this specific dermal cell subset in epidermal proliferation and maturation. These studies may also provide an insight into the role of these factors in skin cancers.Read moreRead less
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.
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.
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.