Alpha-actinin-4 As An Oncogenic Driver And Therapeutic Target In Melanoma
Funder
National Health and Medical Research Council
Funding Amount
$401,786.00
Summary
Despite the recent advances in targeted therapy and immunotherapy, curative treatment of metastatic melanoma remains an unmet health problem. In this project, we will potentially demonstrate that a protein called ACTN4 is abnormally expressed at high levels in melanoma cells and plays an important role for melanoma cell survival and resistance to treatment, and thus identify inhibition of ACTN4, either alone or in combination with other drugs, as a novel approach in the treatment of melanoma.
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.
Therapeutic Targeting Of Ribosome Biogenesis In Cancer And Ribosomopathies
Funder
National Health and Medical Research Council
Funding Amount
$763,845.00
Summary
My fellowship application will build on my international leadership in understanding growth control in human disease. My vision is to uncover the molecular mechanisms governing the loss of normal control of the synthesis of the molecular machines, termed ribosomes, that are responsible for synthesising all cell proteins. I will translate these findings into new paradigms to treat patients suffering from diseases such as cancer and ribosomopathies, that are associated with ribosome dysfunction.
The Role Of ILK In Hedgehog Signaling And Medulloblastoma.
Funder
National Health and Medical Research Council
Funding Amount
$452,248.00
Summary
Molecular signaling pathways regulate normal embryo development, and deregulated signaling by these pathways causes many cancers. Hedgehog (Hh) is a signalling pathway commonly activated by mutations in specific genes to cause cancer, including medulloblastoma, the most common brain tumour of childhood. We have discovered novel protein interactions in the Hh pathway, and will use animal models of Hh-dependent medulloblastoma to investigate new anti-cancer drugs targetting these proteins.
The Pez-TGFbeta-miR200-ZEB1-2 Axis In Breast Cancer
Funder
National Health and Medical Research Council
Funding Amount
$533,541.00
Summary
A feature of late-stage cancer is metastasis - the dissemination of cancer cells to other tissues. Despite advances in treatment of primary cancers, metastatic disease remains the major cause of death in cancer patients. In metastatic cancers, the cells undergo a change that enables them to initially invade the surrounding tissues. We have discovered a novel regulator of the invasive process in tissue culture and this study aims to substantiate its role in breast cancer.
Inhibiting Mutant FGFR2 In Endometrial Cancer By Extracellular Blockade
Funder
National Health and Medical Research Council
Funding Amount
$354,859.00
Summary
Endometrial cancer is a common gynecological cancer in women and new therapies are required to improve survival rates. We have identified mutations in a key cell membrane protein (FGFR2) and shown that endometrial cancer cells with these mutations have altered growth factor dependence. Inhibiting these mutant proteins can result in cell death. By characterizing these mutations and their cellular effects we will be able to develop specific blocking agents for use as potential novel treatments
I am a cancer biologist determining the mechanisms controlling growth and proliferation of cancer cells and use transgenic models of malignancy and genetic approaches to identify new therapies for targeting growth control in the treatment of cancer.
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.