Developmental programming of adult stress responses: early life nutrition permanently alters stress and immune function. Obese children are more likely to grow up to be obese adults than normal-weight children are. Their early life diet may be at least partly to blame. Early life nutrition can also compromise ability to respond to stress or inflammation. This project will investigate how this occurs and if these effects are specific to the developmental period.
How do nutrient-regulated changes in mitochondrial protein acetylation and sirtuin activity affect mitochondrial function and insulin action? Lysine acetylation affects the function of many proteins. This project will examine how excess nutrient availability and altered sirtuin activity affects the acetylation state and function of mitochondrial proteins. This information may identify therapeutic targets to treat diseases associated with mitochondrial dysfunction.
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.
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
Building child health through maternal wellbeing. Chronic diseases partly originate in the health & social circumstances of previous generations, during pregnancy, and in conditions during infancy and childhood. This project will draw from three community studies the researcher established to investigate how aspects of women's health affect their children's health and identify new opportunities for disease prevention.
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
Caged lanthanides for use in photo-dynamic therapy and near infra-red imaging. The early detection and effective treatment of cancer are two critical factors which determine survivability. This project will provide improved drugs for photo-dynamic therapy and develop emissive probes for near infra-red imaging to allow better discrimination between healthy and diseased tissue and improve subsequent treatment.
Can unloading footwear improve clinical care of people with knee osteoarthritis? Osteoarthritis is a public health problem imposing major economic and personal burden. It is the fourth highest cause of morbidity in Australia and national health expenditure in 2007 was $2.03 billion. Footwear can reduce knee load which is linked to disease pathogenesis. Specially-designed unloading shoes will be evaluated in a clinical trial and biomechanical studies to determine their efficacy at reducing sympto ....Can unloading footwear improve clinical care of people with knee osteoarthritis? Osteoarthritis is a public health problem imposing major economic and personal burden. It is the fourth highest cause of morbidity in Australia and national health expenditure in 2007 was $2.03 billion. Footwear can reduce knee load which is linked to disease pathogenesis. Specially-designed unloading shoes will be evaluated in a clinical trial and biomechanical studies to determine their efficacy at reducing symptoms, mechanical mechanism of pain relief, patient sub-groups that best respond to treatment and whether combined treatment with medial arch supports changes knee biomechanics. Outcomes will impact clinical practice and relieve suffering of people with knee osteoarthritis. Findings will also guide future shoe developments for arthritis. Read moreRead less
From causative genes to establishing therapies for patients with neuromuscular diseases. A major focus of this project will be pursuing multiple therapeutic approaches for a class of skeletal muscle diseases, which are most often severe and lethal within the first year of life. It will also hunt down the defective genes in human patients with other neuromuscular diseases and explore how these cause disease.
Inherited determinants of cancer aetiology. Family history of cancer is a strong risk factor for many cancers. This project will aim to identify inherited factors influencing risk of developing cancer and those factors influencing the course of the disease and outcomes.