The Role Of Clathrin In The Spindle Assembly Checkpoint And As An Anti-cancer Target
Funder
National Health and Medical Research Council
Funding Amount
$651,768.00
Summary
Cell division produces two daughter cells. Incorrect localisation and modification of proteins that regulate mitosis cause errors that can lead to cancer. As well as using a unique machinery mitosis uses proteins involved in non-cell cycle pathways. This project investigates the role during mitosis of one such protein: clathrin. We will identify lead clathrin inhibitory compounds, pitstops, that have potential anti-cancer properties, ultimately to be used as a chemotherapy agent.
Cellular And Molecular Mechanisms Of Hedgehog Signaling In Breast Cancer
Funder
National Health and Medical Research Council
Funding Amount
$551,937.00
Summary
Breast cancer cells create the conditions for their own survival by communicating their needs to the healthy cells that surround them. We have previously shown that a molecule known as ‘hedgehog’ transmits biochemical signals between breast cancer cells and healthy cells. When hedgehog is ‘silenced’, tumours shrink and stop their spread. In this application, we will identify the cells receiving the hedgehog signal and identify how they support the growth and spread of breast cancers.
The behaviour of prostate cancer cells is regulated by their surrounding environment known as the stroma. The stroma has been proposed as a therapeutic target, but it is a diverse mix of cells that needs to be specifically targeted. Not all stromal cells are equal; cells surrounding tumours have different features from cells in normal tissue. Therefore, the goal of this project is to directly isolate cancer-associated stromal cells from patient tissue and study their role in cancer progression.
Determination Of The Cellular Origins Of Breast Cancer
Funder
National Health and Medical Research Council
Funding Amount
$705,563.00
Summary
Breast cancer is a highly heterogeneous disease with multiple molecular and histological subtypes. We propose to use novel genetically engineered mice to understand breast inter-tumoral heterogeneity by dissecting the cells of origin of breast cancer in vivo. Initially, we will examine whether long-lived stem or progenitor cells are the targets of breast carcinogenesis induced by a progesterone derivative using our state-of-the-art multi-coloured reporter models to track the cells in vivo.
Apoptosis And Stem Cells In Cancer Development And Therapy
Funder
National Health and Medical Research Council
Funding Amount
$22,852,198.00
Summary
To improve cancer therapy, we are studying two cancer hallmarks: enhanced cell survival and stem cell-like behaviour. As we discovered, cell death is often blocked in cancer cells. Hence, we are attempting to develop drugs that flip the natural ‘cell death switch’. Stem cells are rare cells that generate entire tissues, as we showed for the breast. Certain cancers may be driven by ‘rogue’ stem cells. If so, eradication of these rare cells within the bulk tumour may require novel therapies.
Deciphering Breast Cancer Heterogeneity To Improve Breast Cancer Outcomes
Funder
National Health and Medical Research Council
Funding Amount
$851,980.00
Summary
Breast cancer is a very heterogeneous disease. Patients are often treated in a ‘one size fits all’ approach, but response to therapy remains quite disparate. To better personalise therapy, there is a pressing need to define the precise cell types and initiating genetic events that give rise to breast cancer. This application is focussed on understanding the molecular and cellular origins of breast cancer, with the potential of identifying new prognostic markers and therapeutic targets.
Prof Lindeman's laboratory, co-headed with Dr Visvader, has played an influential role in the identification of mammary stem and progenitor cells, elucidation of the mammary epithelial cell hierarchy and gaining insights into how female hormones regulate mammary gland development and cancer. In parallel, I have established translational research platforms such as patient-derived tumour xenograft (PDX) models, which offer powerful preclinical models to test new drugs.
The Microniche: A Novel In-vitro And In-vivo Prostate Cancer Model System
Funder
National Health and Medical Research Council
Funding Amount
$561,012.00
Summary
Maintaining primary prostate cancer cells (PCa) in vitro remains an enormous challenge for the field, and this obstructs efforts to systematically characterize cell behaviour and quantify drug response. Our group recently developed a 3-demsensional (3D) organoid culture system that does maintain PCa in vitro, and here we will integrate this technology with our 3D bone maorrow niche model system to better characterize PCa bone metastases and identify new clinical treatment regimes.
Restoration Of P53 Activity In Tumours: A New Approach Involving The P53 Coactivator ANKRD11.
Funder
National Health and Medical Research Council
Funding Amount
$465,990.00
Summary
p53 is an important protein that functions as the body�s defence mechanism against cancer. Mutation of p53 is observed in over half of all tumours. Not only do these cancer mutations abolish the ability of p53 to protect against cancer, but it also endows the tumours with an ability to spread throughout the body, or metastasize. In this research project, we will identify and develop targets that will not only prevent the spread of new tumours, but it will also re-activate the anti-cancer functio ....p53 is an important protein that functions as the body�s defence mechanism against cancer. Mutation of p53 is observed in over half of all tumours. Not only do these cancer mutations abolish the ability of p53 to protect against cancer, but it also endows the tumours with an ability to spread throughout the body, or metastasize. In this research project, we will identify and develop targets that will not only prevent the spread of new tumours, but it will also re-activate the anti-cancer function in mutant p53 leading to tumour regression.Read moreRead less