I am an orthopaedic surgeon and clinician-scientist based at Sydney’s largest children’s hospital. My goal is to improve treatments for children with traumatic injuries and bone deformity. I have worked in bone research for over 20 years. My current research interests are finding new treatments for drug-resistant bacterial infections, treating genetic bone disease, and developing new medical devices to help children’s bones grow straight.
Trabecular Architecture During Growth - Does It Determine Metaphyseal Peak Bone Strength In Adulthood?
Funder
National Health and Medical Research Council
Funding Amount
$165,339.00
Summary
Skeletal fragility is common is elderly people but has its origin in childhood. Strong bone established during growth will provide more protection against occurrence of fragility fracture in old age. Identifying individuals during childhood who are at high risk of skeletal fragility, and early intervention is a strategic approach managing the burden of skeletal fragility on the ageing population.
The Molecular Mechanisms Controlling Maintenance Of Osteogenic Precursor Cells And Skeletal Tissue Regeneration
Funder
National Health and Medical Research Council
Funding Amount
$234,750.00
Summary
Within human bone marrow there exists a rare population of bone marrow stromal stem cells (BMSSCs) able to develop into the different cell types that form haematopoietic supportive stroma and surrounding skeletal tissue. There has been alot of interest of late in the potential of BMSSCs as a cellular based therapy to treat and manage bone fractures or bone loss caused by disease. Increasing evidence suggests that decreased bone mass due to osteoporosis dos not purely result in an increase of bon ....Within human bone marrow there exists a rare population of bone marrow stromal stem cells (BMSSCs) able to develop into the different cell types that form haematopoietic supportive stroma and surrounding skeletal tissue. There has been alot of interest of late in the potential of BMSSCs as a cellular based therapy to treat and manage bone fractures or bone loss caused by disease. Increasing evidence suggests that decreased bone mass due to osteoporosis dos not purely result in an increase of bone resorption by osteoclasts, but may also occur through a decline in the number of bone forming cells called osteoblasts or their progenitors. Fracture non-union, prosthetic loosening and the replacement of large defects in bone are common and difficult problems. The use of autologous bone cells generated from isolated BMSSCs in combination with bio-compatible implant materials would provide a novel solution for the treatment of these problems, avoiding the use of autografts and allografts of bone with all their associated difficulties. However, large numbers of ex vivo expanded BMSSCs are currently required to heal even small bone defects in animal models. This is compounded by the decline in proliferation rates and bone forming capacity of BMSSCs during prolonged expansion in culture. An improved understanding of the genes that regulate the proliferation and differentiation of BMSSCs in vitro is therefore an essential prerequisite for the effective management of bone fracture and bone loss. We propose to genetically manipulate the expression of genes in BMSSCs, that are known to regulate cellular growth and development inorder to maintain the growth of stem cell populations in vitro and to extend their capacity to form bone when transplanted in vivo.Read moreRead less
The Role Of TWIST Family Basic Helix-Loop-Helix Transcription Factors In Bone Cell Commitment, Function And Repair
Funder
National Health and Medical Research Council
Funding Amount
$485,928.00
Summary
In developed countries, projected estimates predict an alarming trend of a two to three fold increase in the number of fractures that require surgical intervention and rehabilitation therapy in the coming decades as a consequence of an aging population. Fracture healing is a complex physiological process that involves the coordinated participation of different bone marrow cells, immune cells and skeletal progenitor cells. Multiple factors regulate interactions between these cell types that influ ....In developed countries, projected estimates predict an alarming trend of a two to three fold increase in the number of fractures that require surgical intervention and rehabilitation therapy in the coming decades as a consequence of an aging population. Fracture healing is a complex physiological process that involves the coordinated participation of different bone marrow cells, immune cells and skeletal progenitor cells. Multiple factors regulate interactions between these cell types that influence the capacity of bone cell progenitors to develop into functional bone forming cells known as osteoblasts. An understanding of the fracture healing is critical for the future advancement of fracture treatment, and for identifying the mechanisms of skeletal growth and repair as well as the causes of aging and disease. This proposal seeks to identify critical regulatory molecules that act to mediate bone cell progenitor recruitment and development during bone fracture repair.Read moreRead less
Osteosarcoma is the most common cancer of bone. It osurs most frequently in childhood (teenage years) and current therapy is limited to surgery and chemotherapy. We have developed a new model of osteosarcoma that displays a high degree of similarity to human osteosarcoma. We aim to further understand this model and apply these findings to help treat human osteosarcoma.
Effects Of Ephrin-Eph And PTHrP Signalling On Osteosarcoma.
Funder
National Health and Medical Research Council
Funding Amount
$646,486.00
Summary
Osteosarcoma (OS) is the most common bone cancer in children, with ~170 cases per year in Australia. We used genetic mutation of mice to induce OS that is very similar to human OS. The OS produces parathyroid hormone-related protein and ephrins and responds to both proteins. We will study how the cancer develops and spreads, and how this is affected by these two pathways, both of which are implicated in cancer development, and could be targets for treatment.
Molecular Studies Of Dentine Phosphophoryn And Development Of A Biomimetic Dental Restorative Material.
Funder
National Health and Medical Research Council
Funding Amount
$444,750.00
Summary
This project involves the study of a protein that is found in teeth and is responsible for the development of dentine. The project involves characterisation of this protein and its interaction with calcium phosphate mineral using a variety of techniques. The information obtained will allow the synthesis of a peptide that will mimick the function of phosphophoryn. This peptide will be used together with stabilized amorphous calcium phosphate in a novel dental restorative material that will help p ....This project involves the study of a protein that is found in teeth and is responsible for the development of dentine. The project involves characterisation of this protein and its interaction with calcium phosphate mineral using a variety of techniques. The information obtained will allow the synthesis of a peptide that will mimick the function of phosphophoryn. This peptide will be used together with stabilized amorphous calcium phosphate in a novel dental restorative material that will help protect the surrounding tooth tissue.The outcome will be an improved understanding of the design principles used by nature to engineer teeth. The significance is the potential development of biocompatible, superior dental restorative materials.Read moreRead less
Characterisation Of Proteins Involved In Biomineralisation Processes
Funder
National Health and Medical Research Council
Funding Amount
$234,175.00
Summary
This project involves the study of two proteins that associate with calcium and phosphate. Phosphophoryn is found in teeth and is responsible for the development of dentine in teeth. Osteopontin is a multi-functional protein found in a variety of tissues as well as in bone and in milk. Its functions in bone and milk are unknown although it is believed to be involved in bone remodelling. This project involves characterisation of these two proteins and their interactions with calcium phosphate min ....This project involves the study of two proteins that associate with calcium and phosphate. Phosphophoryn is found in teeth and is responsible for the development of dentine in teeth. Osteopontin is a multi-functional protein found in a variety of tissues as well as in bone and in milk. Its functions in bone and milk are unknown although it is believed to be involved in bone remodelling. This project involves characterisation of these two proteins and their interactions with calcium phosphate mineral using a variety of techniques. The outcome will be an improved understanding of the design principles used by nature to engineer teeth and bone. The significance is the potential development of biocompatible apatite-based biomaterials for both tooth and bone.Read moreRead less
Understanding Skeletal Development: A Non-proteolytic Mechanism Of Aggrecan Resorption In The Growth Plate
Funder
National Health and Medical Research Council
Funding Amount
$563,044.00
Summary
Bone formation requires resorption of a cartilage template. We challenge the dogma that cartilage resorption is only by PROTEASES, and propose instead that GLYCOSIDASES might also be involved. Aims: Demonstrate that chondrocytes release glycosidases that are important for bone formation. Significance: New information for the design of reconstructive therapies for people with congenital and acquired limb deficiencies or inherited disorders such as arthritis and chondrodysplasias may be gained.