An exciting area of drug discovery involves targeting Hippo pathway proteins, particularly one called YAP, which were discovered by members of our research team and which are highly active in some cancer cells, making them grow and spread. We will test whether YAP is a potential drug target to prevent or treat melanoma, a deadly type of cancer that usually arises in the skin but also internal organs and the eye. If so, we would fast-track these drugs for testing in patients via clinical trials.
Defining The Role Of Microphthalmia-associated Transcription Factor (MITF) In Melanoma Heterogeneity By Real-time Cell Cycle Imaging
Funder
National Health and Medical Research Council
Funding Amount
$613,705.00
Summary
Metastatic melanoma is highly therapy-resistant. Modern targeted therapy is promising but suffers from rapid onset of drug resistance. Tumours consist of zones of fast growing cells next to zones of dormant cells. This tumour heterogeneity is one of the reasons for cancer drug resistance, as cells in different growth states respond differently to drugs. By understanding the causes of tumour heterogeneity we will set the basis for innovative clinical approaches against this devastating disease.
Pyk2: A Central Mediator Of Gonadotropin Action In Ovarian Cancer
Funder
National Health and Medical Research Council
Funding Amount
$334,053.00
Summary
Ovarian cancer generally presents at an advanced stage where 5 yr survival is less than 25%. Elevated levels of specific hormones after menopause may increase the risk of this cancer. We have shown that a protein called Pyk2 is activated in response to these hormones and may have significant roles in ovarian cancer cell migration, invasion and proliferation. This project will investigate the role of this protein, with the goal of improved therapeutics for women with ovarian cancer.
Targeting mitochondria with mitocans to treat cancer: mechanistic aspects. Mitochondria are the power-house of the cell and also the reservoir of proteins causing the demise of cancer cells, therefore suppressing tumour progression. This project proposes a novel way to modify certain compounds, increasing their level in mitochondria in order to maximise their anti-cancer effect.
I am a cell biologist/geneticist focusing on understanding tumourigenesis. Cancer is a multigenic and complicated disease, involving interactions between the tumour and normal tissue. I use the genetically tractable model organism, the vinegar fly, Drosophila, to model cancer in situ and identify novel genes that drive cancer. My 5 year career plan is to use the Drosophila system to model cooperative tumourigenesis in epithelial and brain tissues and translate this to human cancer.
Telomere Structural Abnormalities In Cells Using Alternative Lengthening Of Telomeres
Funder
National Health and Medical Research Council
Funding Amount
$522,122.00
Summary
The continuing growth of cancers depends on their cells being able to prevent shortening of chromosome ends (telomeres). Some cancers, including very aggressive brain and connective tissue tumours, achieve this via the Alternative Lengthening of Telomeres (ALT) process. We have evidence that the telomere structure of normal cells prevents ALT. Here we will examine how the telomere structure of ALT-positive cancer cells is changed, and whether reversing these changes inhibits ALT.
Characterisation Of A Novel PI3-kinase Signal Terminating Enzyme In Breast Cancer.
Funder
National Health and Medical Research Council
Funding Amount
$633,512.00
Summary
Breast cancer is the most common malignancy among females, affecting 1 in 9 women before the age of 85. Normally cells divide only when they receive a stimulus from a hormone or growth factor. The PI3K pathway which responds to these stimuli has been implicated in cancer where cells divide uncontrollably and invade surrounding tissue. We have identified a potential cancer suppressing gene, PIPP, which turns off PI3K growth signals. We aim to characterize the role of PIPP in breast cancer.
Characterisation Of The Tumour Suppressor Function Of Caspase-2
Funder
National Health and Medical Research Council
Funding Amount
$605,096.00
Summary
Aberrant cell death (apoptosis) is associated with many diseases including cancer. Apoptosis is mediated by a group of enzymes called caspases. Recently we have discovered that one of these enzymes, caspase-2, acts as a tumour suppressor. We now wish to validate this finding in several preclinical models of cancer and understand precisely how caspase-2 works to safeguard cells against cancer development. These studies will help better understand cancer and ways to treat it.
How do mechanical cues regulate tissue renewal and tumour progression? Imbalances between cell production and cell death in tissues can be catastrophic, leading to major global health issues such as cancer. This project will use modified mice and protein-protein interaction based techniques to identify how changes in the mechanical properties of tissues regulate the balance between cell production and cell death.
Role of endocytic mechanisms in mammalian cytokinesis. Cell division requires endocytic proteins and failed cell division can contribute to cancer. This project aims to understand how endocytic proteins function to complete cell division successfully and has implications for the development of chemotherapeutic agents to treat cancer.