GENETIC PREDICTION OF FRACTURE IN A RISK-STRATIFIED POPULATION
Funder
National Health and Medical Research Council
Funding Amount
$363,000.00
Summary
Osteoporosis is a condition characterised by excessive bone loss and impaired bone quality, which ultimately results in fracture with minimal trauma. Osteoporosis affects 27% of women and 11% of men aged 60 years or above in the community, and costs Australia around $7 billion each year. Individuals with low bone mineral density (BMD) have a significantly higher risk of fracture than those with normal BMD. In the long-term (14-year) Dubbo Osteoporosis Epidemiology Study, more than half of indivi ....Osteoporosis is a condition characterised by excessive bone loss and impaired bone quality, which ultimately results in fracture with minimal trauma. Osteoporosis affects 27% of women and 11% of men aged 60 years or above in the community, and costs Australia around $7 billion each year. Individuals with low bone mineral density (BMD) have a significantly higher risk of fracture than those with normal BMD. In the long-term (14-year) Dubbo Osteoporosis Epidemiology Study, more than half of individuals with osteoporosis (e.g., low BMD) did not sustain a fracture, while approximately 60% of fracture cases had BMD above the high risk levels. Thus, BMD alone is not a good discriminant of fracture versus non-fracture cases. It is widely known that the liability to fracture is determined in part by genes. Previous studies, including from our group, have suggested a number of candidate genes that are associated with fracture risk. The fundamental issue that this study is concerned is that how and whether genetic markers could be used to facilitate case finding. It is proposed that common variations of certain genes are associated with fracture risk independent of BMD. That is, they can identify individuals at relatively high and low fracture risk after stratification for BMD. Hence, some markers may identify those individuals likely (and unlikely) to fracture even with low (osteoporotic) BMD. Similarly, some, possibly the same, markers may identify individuals at high risk of fracture despite relatively good (ie non-osteoporotic) BMD. It is further proposed that no single gene will achieve this outcome, but rather a small set of such gene polymorphisms will provide clinically useful risk information. This effect is entirely analogous to the use of clinical risk indicators (eg, age, weight, sex, family history, etc) to assess the risk of future fracture.Read moreRead less
Myeloma Plasma Cell Dormancy - 'Eradicating The Sleeping Giant'
Funder
National Health and Medical Research Council
Funding Amount
$834,428.00
Summary
Multiple myeloma is a fatal cancer that develops in the skeleton. Current therapies are initially effective, but patients develop resistance and the disease returns. This makes the search for drugs to overcome resistance a priority. Myeloma cells can hide in bone in a dormant state where they are insensitive to chemotherapy. We have identified new drug targets in dormant cells. We are investigating whether these new targets can be used eradicate myeloma cells and cure the disease.
The Role Of Force-sensing Ion Channels In Melanoma Migration
Funder
National Health and Medical Research Council
Funding Amount
$553,848.00
Summary
Metastasis of melanoma cells away from the primary tumour site carries a very poor patient prognosis.This research aims to characterise a novel signalling pathway that can regulate the migration (movement) of melanoma cells. This signalling pathway depends on force-sensing platforms that can rapidly convert physical inputs from the environment into an electrical signal within the cell. We are working to understand how these force-sensors function.
The cells that produce and maintain our cartilage, known as chondrocytes, do so by sensing changes in the mechanical environment, but precisely how chondrocytes detect these changes is not known. We are investigating the role of ion channels that are opened in direct response to mechanical movements within the cartilage.This project plans to identify the specific molecules that are participating in this process and to determine if they are therapeutic targets for treatment of osteoarthritis
This study aims to elucidate central pathways which can be manipulated to drive the storage of excess energy away from fat and instead directing it into the production of bone mass. Having identified leptin-responsive NPY neurons as important in the control of energy partitioning, we will focus on manipulating these neurons in the hypothalamus using innovative technology to alter body composition. This research has the potential to result in novel treatments for obesity and osteoporosis.
Transient Tissue ‘priming’ Via FAK Inhibition To Impair Pancreatic Cancer Progression And Improve Sensitivity To Gemcitabine/Abraxane
Funder
National Health and Medical Research Council
Funding Amount
$643,848.00
Summary
The success of cancer drugs is dependent on many factors including the properties of the tumour tissue. As a tumour grows it changes the tissue around it, and this affects response to treatment. Combining classical biology with engineering to generate 3D models that mimic tumours, along with cutting-edge imaging technology and mouse models, we will target FAK-controlled cancer cell pathways that sense tissue changes, together with already approved cancer drugs to improve patient outcome.
Single-cell Optical Window Imaging In CDK1-FRET Biosensor Mice To Assess Tissue Stiffness And Optimise Delivery And Therapeutic Response To Gemcitabine/Abraxane In Pancreatic Cancer.
Funder
National Health and Medical Research Council
Funding Amount
$676,979.00
Summary
Inefficient drug response in solid tumour tissue is commonly a limiting factor in the clinical effectiveness of cancer therapies. Using cutting-edge imaging technology and 3D models that mimic the disease, we have mapped areas of poor drug response within distinct regions of tumours. Here, we pinpoint and specifically target key factors limiting efficient drug targeting in order to improve the encouraging anti-cancer profile of the new drug combination Gemcitabine/Abraxane in pancreatic cancer.
Biosensor Imaging In Preclinical Pancreatic Cancer Targeting: Taking Cancer Targeting To New Dimensions.
Funder
National Health and Medical Research Council
Funding Amount
$640,210.00
Summary
Using cutting-edge imaging technology and 3D models that mimic cancer, we can map areas of poor drug response within distinct 'stages' or regions of tumours. Here, we pinpoint and specifically target key factors limiting efficient drug response in order to improve the encouraging anti-cancer profile of new or current drugs in pancreatic cancer.