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.
A Novel Protease And Growth Factor Regulated Signalling System In Ovarian Cancer
Funder
National Health and Medical Research Council
Funding Amount
$856,743.00
Summary
Ovarian cancer is the leading cause of gynaecologic cancer death. Our project focuses on the role in ovarian cancer of a cellular receptor called CDCP1. We have previously shown that CDCP1 promotes growth and spread of ovarian tumours. Recently we have generated new data indicating that CDCP1’s activity is markedly increased by other proteins called proteases and growth factors. In this project we will define how these new pathways function, and if their blockade impedes ovarian cancer.
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.
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.
Targeting Homeobox Genes In Acute Myeloid Leukaemia
Funder
National Health and Medical Research Council
Funding Amount
$658,739.00
Summary
Acute myeloid leukaemia (AML) is a common blood cancer with dire clinical prognosis due to a lack of targeted molecular therapies. In this proposal we will identify new ways of targeting transcription factor proteins that are overexpressed in AML and promote leukaemia by repressing normal cellular growth controls. This may lead to novel methods to target leukaemic stem cells to specifically eliminate myeloid leukemia
How Does The Tumour Suppressor: Nerfin-1 Prevent Dietary Dependent Tumour Growth?
Funder
National Health and Medical Research Council
Funding Amount
$630,942.00
Summary
The influence of diet has been linked to tumour growth for decades, however, there is little scientific evidence to support or disprove this. In this study, we will assess the effect of diet on tumours in fruit flies. The metabolic genes which regulate the growth of fly tumours will then be studied in human brain tumours. Our studies will ultimately shed light on how tissue growth is controlled by dietary intake, and have the potential to inform the way that we treat and manage human cancers.