The critical role of the class III histone deacetylase SIRT2 in stabilizing N-Myc oncoprotein. Cancer is the commonest cause of death from disease in children. Neuroblastoma is the commonest solid tumor in early childhood. This project will investigate the critical roles of SIRT2 protein in increasing the expression of N-Myc oncoprotein and consequently inducing neuroblastoma, and SIRT2 inhibitors as anticancer agents.
A new Src, PKCdelta and Akt regulated protease activated receptor system in metastasis. In contrast with localised cancer which can often be cured, curative treatment is generally not possible for cancer that has spread. This project will characterise a protein that drives the spread of cancer and to develop new approaches to treat patients at risk of developing these aggressive tumours that spread to other organs.
Molecular hallmarks of androgen receptor targeting in prostate cancer. There is a critical need in oncology drug development for better biomarkers of response to prostate cancer therapies, clinically to assist with treatment decision making, and pre-clinically to facilitate translation of emerging agents into clinical practice. Using a unique explant culture model, this project will identify protein and lipid markers that can be used to accurately and reliably assess response to androgen recepto ....Molecular hallmarks of androgen receptor targeting in prostate cancer. There is a critical need in oncology drug development for better biomarkers of response to prostate cancer therapies, clinically to assist with treatment decision making, and pre-clinically to facilitate translation of emerging agents into clinical practice. Using a unique explant culture model, this project will identify protein and lipid markers that can be used to accurately and reliably assess response to androgen receptor (AR)-targeting therapies in human prostate tumours. The identification and functional assessment of these biomarkers will identify those that can be used as surrogate endpoints in clinical trials, facilitate earlier approval of investigational agents and lead to improved options for therapeutic management of prostate cancer.Read moreRead less
Crosstalk between breast cancer cells and the microenvironment to promote metastasis. Breast cancer spread (metastasis) to distant tissues is usually fatal. It is now clear that cross-talk between cancer cells and other normal cells is essential for metastasis and previous studies have discovered two key mechanisms: tumour cell suppression of immune defence pathways to escape immune recognition, and activation of proteases to promote invasion and blood vessel growth. Using unique models and cell ....Crosstalk between breast cancer cells and the microenvironment to promote metastasis. Breast cancer spread (metastasis) to distant tissues is usually fatal. It is now clear that cross-talk between cancer cells and other normal cells is essential for metastasis and previous studies have discovered two key mechanisms: tumour cell suppression of immune defence pathways to escape immune recognition, and activation of proteases to promote invasion and blood vessel growth. Using unique models and cellular imaging, this project aims to investigate the cell specific functions of these pathways and the therapeutic potential of altering their expression and function. This project may lead to the development of novel predictors of metastasis in patients and new targeted therapeutics to prevent breast cancer spread.Read moreRead less
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.
Understanding endocrine tumorigenesis - opportunities for new diagnostics and therapies. This project will generate new knowledge significant for improving cancer diagnosis and designing new therapies for cancer patients as we embrace the personalised medicine era. Specific focus is on endocrine tumours. This research has as its aim improved survival for people diagnosed with cancer.
EGFR-directed radioimmunotherapy combined with chemotherapy and DNA repair inhibition: development towards clinical application for aggressive cancers. Pancreatic ductal adenocarcinoma (PDAC) and triple negative breast cancer (TNBC) are aggressive diseases which lack effective therapies in clinical use. A novel and curative therapy was developed against PDAC and TNBC which involves targeted radiotherapy combined with chemotherapy and DNA damage response inhibition. This project will develop a “p ....EGFR-directed radioimmunotherapy combined with chemotherapy and DNA repair inhibition: development towards clinical application for aggressive cancers. Pancreatic ductal adenocarcinoma (PDAC) and triple negative breast cancer (TNBC) are aggressive diseases which lack effective therapies in clinical use. A novel and curative therapy was developed against PDAC and TNBC which involves targeted radiotherapy combined with chemotherapy and DNA damage response inhibition. This project will develop a “preclinical data package” comprising a biological rationale and preclinical evidence of safety and efficacy that together would justify an early phase clinical trial. This package includes the choice of formulations, mechanism of action and safety studies. This development will have an immediate impact for PDAC and TNBC patients and a future impact on other EGFR-positive cancers.Read moreRead less
Defining targets and generating tools/therapeutic agents for prevention, diagnosis and therapy of atherothrombosis. Atherosclerosis and its complications such as myocardial infarction and stroke are a major cause of death and disability in Australia and worldwide. The proposed research program investigates new therapeutic targets and concepts (e.g. targeting of stem cells) to treat atherosclerosis and aims to develop new therapeutic agents using modern biotechnological methods. The project furth ....Defining targets and generating tools/therapeutic agents for prevention, diagnosis and therapy of atherothrombosis. Atherosclerosis and its complications such as myocardial infarction and stroke are a major cause of death and disability in Australia and worldwide. The proposed research program investigates new therapeutic targets and concepts (e.g. targeting of stem cells) to treat atherosclerosis and aims to develop new therapeutic agents using modern biotechnological methods. The project further aims to develop nanoparticle-based diagnostic tools to identify and preventatively treat atherosclerotic plaques that are prone to cause myocardial infarction. The expected outcome will provide direct benefit to patients and create new economic opportunities in Australian bio-/nanotechnology.Read moreRead less
Targeting genes elevated in the athlete's heart to improve function of the failing heart. Cardiovascular disease affects about 3.7 million Australians and heart failure ranks as one of the major killers, representing a huge burden on our health care system and economy. This situation is likely to get worse with an increasing ageing population. Current therapeutics for heart failure patients largely delay disease progression but generally fail in significantly improving heart function and quality ....Targeting genes elevated in the athlete's heart to improve function of the failing heart. Cardiovascular disease affects about 3.7 million Australians and heart failure ranks as one of the major killers, representing a huge burden on our health care system and economy. This situation is likely to get worse with an increasing ageing population. Current therapeutics for heart failure patients largely delay disease progression but generally fail in significantly improving heart function and quality of life. The proposal has focused on targeting the protective effects of 'good' heart growth by identifying genes elevated in the heart in response to exercise. Targeting genes elevated in the athlete's heart to improve function of the failing heart represents a new strategy for the treatment of heart failure.Read moreRead less