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
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.
Dissecting the shared genetic architecture of psychiatric and psychological traits with application to prediction of genetic risk. Identification of the early phase of psychiatric disorders is considered critical for early intervention which is the essence of prevention. At present, the main obstacle to targeted early intervention strategies in psychiatric disorders is the non-specific nature of early stage symptoms. Many psychiatric disorders present with symptoms of depressed mood and anxiety ....Dissecting the shared genetic architecture of psychiatric and psychological traits with application to prediction of genetic risk. Identification of the early phase of psychiatric disorders is considered critical for early intervention which is the essence of prevention. At present, the main obstacle to targeted early intervention strategies in psychiatric disorders is the non-specific nature of early stage symptoms. Many psychiatric disorders present with symptoms of depressed mood and anxiety in the early stages, yet best intervention treatments are dependent on the final (unknown) diagnosed disorder. Prediction of genetic risk is likely to make an important contribution for identification of individuals at risk of specific psychiatric disorders so that the best early intervention treatment can be administered. Read moreRead less
Imaging genetics in schizophrenia and bipolar disorder: shared neurocognitive endophenotypes. Combined, schizophrenia and bipolar disorder afflict approximately 506,000 Australians at any one time, and are leading causes of disability and national economic burden. This study will delineate genetic underpinnings for these conditions in association with specific neurocognitive dysfunctions that are common to both disorders. These findings have important implications for the implementation of perso ....Imaging genetics in schizophrenia and bipolar disorder: shared neurocognitive endophenotypes. Combined, schizophrenia and bipolar disorder afflict approximately 506,000 Australians at any one time, and are leading causes of disability and national economic burden. This study will delineate genetic underpinnings for these conditions in association with specific neurocognitive dysfunctions that are common to both disorders. These findings have important implications for the implementation of personalised pharmaceutical treatments on the basis of genotype, and the development of therapeutic agents to target cognitive function. These results will also aid detection of premorbid psychotic illness in young individuals who may benefit from early intervention that may thwart the illness trajectory. Read moreRead less
The development of tools to study carbohydrate-processing enzymes implicated in human disease. Diseases caused by improper function of carbohydrate-processing enzymes are a major health burden. This research aims to find ways to restore the function of these enzymes bringing a better quality of life to people suffering from these diseases.