Deciphering The Function Of Caspase-2 In DNA Damage Response And Tumour Suppression
Funder
National Health and Medical Research Council
Funding Amount
$808,007.00
Summary
Aberrant cell death and DNA damage response (DDR) are hallmarks of tumourigenesis. Recently we have discovered that an enzyme, caspase-2, previously implicated in cell death execution, also works in DDR and acts as a tumour suppressor. We now wish to validate these finding in preclinical models of cancer and understand precisely how caspase-2 safeguards against cancer development. These studies will help better understand tumourigenesis and may lead to the discovery of new drug targets.
The Role Of Sidt2 In Cell Proliferation And Tumour Suppression
Funder
National Health and Medical Research Council
Funding Amount
$531,053.00
Summary
This project seeks to understand the function of a gene known as Sidt2. Our preliminary results suggest that Sidt2 not only controls how normal cells divide but also prevents cancer cell growth. We have now engineered mice that lack Sidt2, and will study the cellular and molecular pathways that are disrupted following loss of Sidt2. This work should provide important insights into how both normal and cancer cells grow, and will hopefully identify new targets for anti-cancer treatment.
LRH-1 is a protein that is inappropriately present in cancers of the breast and other tissues. It causes cancer cells to divide and multiply, and therefore it is important to block its activity. There are, however, no treatments available that block LRH-1. This proposal brings together a team of researchers with broad experience. We will use high throughput technologies to identify and characterize novel LRH-1 inhibitors, and demonstrate their efficacy in reducing the growth of cancer cells.
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.
Cell Cycle Tracking Of B Cell Differentiation And Mutation
Funder
National Health and Medical Research Council
Funding Amount
$719,666.00
Summary
Antibody-mediated immunity to infectious diseases requires the proliferation of infection-specific antibody-producing B cells. The fate of responding B cells is linked to this proliferation according to a poorly understood division-based “map”. This project will track B cell fates in vivo using advanced imaging techniques. We will define differences between B cells from young versus old individuals that may explain why the effectiveness of the immune system declines with age.
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.
EAR2: A Novel Driver Of Breast Cancer Proliferation
Funder
National Health and Medical Research Council
Funding Amount
$725,476.00
Summary
Drugs that block oestrogen are effective breast cancer treatments, but many patients are resistant to their effects. This research addresses a protein known as EAR2, that is elevated in breast cancer tissue compared to normal breast. We hypothesise that EAR2 drives breast cancer cell proliferation, and will test this using cell lines and mouse models. We will validate EAR2 as a new therapeutic target, benefitting patients underserved by current hormone therapies.
Role Of The Drug Metabolising Enzyme Arylamine N-acetyltransferase 1 In Breast Cancer
Funder
National Health and Medical Research Council
Funding Amount
$600,196.00
Summary
The current project will identify the molecular mechanism(s) that underpins the significant changes in phenotype seen in a range of human cancer cells. The expected outcomes will be to demonstrate that NAT1 is critical for the clearance of pABG in cancer cells. The results will be important in the context of understanding this family of intracellular enzymes and will change the current thinking on the function of the arylamine N-acetyltransferase in normal and cancer cells.
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.
Understanding The Regulation Of Kidney Morphogenesis In Order To Improve Renal Development
Funder
National Health and Medical Research Council
Funding Amount
$683,040.00
Summary
Chronic kidney disease is a growing burden to the health system. The long term health of your kidneys is influenced by the number of functional units, nephrons, present in each kidney, a feature that is determined before birth. If we could influence this number, we may be able to reduce the risk of kidney disease in later life for at risk populations, including the Aboriginal community. This study will investigate the stem cells that form the nephrons, how the process occurs and how it can be in ....Chronic kidney disease is a growing burden to the health system. The long term health of your kidneys is influenced by the number of functional units, nephrons, present in each kidney, a feature that is determined before birth. If we could influence this number, we may be able to reduce the risk of kidney disease in later life for at risk populations, including the Aboriginal community. This study will investigate the stem cells that form the nephrons, how the process occurs and how it can be influenced.Read moreRead less