Tyrosine Kinase Receptor C-ros-oncogene 1 Mediates Twist-1 Haploinsufficiency Induced Craniosynostosis In Children: A Novel Therapeutic Target
Funder
National Health and Medical Research Council
Funding Amount
$562,863.00
Summary
Children with Saethre-Chotzen syndrome exhibit premature fussed coronal sutures, and other skull/ skeletal malformations. Surgical intervention is the only treatment option to ensure optimal cognitive and skeletal development. Our studies have identified a candidate molecular pathway that regulates bone formation by cranial bone cells from these patients. Targeting these key molecular signalling components with chemical inhibitors will help prevent the premature fusion of cranial sutures.
Gene Mining For Novel Molecular Determinants Of The Skeleton
Funder
National Health and Medical Research Council
Funding Amount
$633,447.00
Summary
Musculoskeletal conditions affect over 6 million Australians and research has shown that genetic background strongly influences development of these disorders. This project will identify genes that have a role in controlling bone and joint architecture. Identification of these genes will assist in the development of treatments targeting bone disorders and allow screening for these genes to provide an opportunity for people to take preventative action to improve bone and joint health.
Histone Demethylase KDM6A Is A Novel Target For Treating Craniosynostosis In Children With Saethre-Chotzen Syndrome
Funder
National Health and Medical Research Council
Funding Amount
$548,854.00
Summary
Children with Saethre-Chotzen syndrome exhibit premature fused coronal sutures, and other skull/ skeletal malformations. Surgical intervention is the only treatment option to ensure optimal cognitive and skeletal development. Our studies have identified a candidate molecular pathway that regulates bone formation by cranial bone cells from these patients. Targeting this key molecular regulator with chemical inhibitors will help prevent the premature fusion of cranial sutures.
The primary aim of this grants to determine how HIV spreads through our immune system. The above knowledge will determine key Achille’s Heel moments in the HIV life cycle and thus lead to better therapeutic HIV treatments/prevention.
The Role Of Osteocytes In Particle Induced Osteolysis
Funder
National Health and Medical Research Council
Funding Amount
$457,196.00
Summary
Hip replacements often fail due to the loss of adjacent bone. Metal or polyethylene particles are produced as the prosthesis bearing surface wears but how do these particles lead to bone loss? Our work suggests involvement of osteocytes within the bone mineral, which are increasingly understood to drive bone physiology and pathology. We will explore the role of the osteocytes by examining their response to particles, which may identify a new target to prevent particle-induced bone loss.
Targeting Bone Marrow Lesions To Find Interventions In The Progression Of Osteoarthritis
Funder
National Health and Medical Research Council
Funding Amount
$467,395.00
Summary
It is essential to elucidate the underlying cause(s) of osteoarthritis because our current level of understanding of this condition has failed to produce effective treatments. Lesions in the bone under the cartilage (BMLs), seen using MRI, have strong potential value for the objective monitoring and management of OA. However, because the nature of BMLs is not well understood, the aim of this application is to perform a comprehensive study of BMLs in OA bone.
The Role Of Co-signalling Receptors In Cytotoxic Lymphocyte Activity During Infection And Cancer
Funder
National Health and Medical Research Council
Funding Amount
$739,657.00
Summary
Cytotoxic lymphocytes (CLs) are immune cells that detect and kill cancer cells. CLs recognise ‘stress’ proteins on cancer cells through specialised receptors, and this provides the signal for them to kill. However, some cancer cells, such as leukemic cells, can interfere with this recognition to avoid killing by immune cells. This project will investigate the mechanism of recognition and killing of cancer cells by CLs, using both mouse models and cells from patients with acute myeloid leukemia.
How Do Bone-active Drugs Increase Patient Survival?
Funder
National Health and Medical Research Council
Funding Amount
$613,952.00
Summary
Bisphosphonates are a class of drugs used to prevent bone destruction in diseases such as osteoporosis. Evidence is emerging that these drugs also act on cells outside the skeleton to have additional beneficial effects, for example prolonging patient survival. This project will identify the cells affected and the mechanisms involved. With this knowledge, these drugs could be used more effectively and in different ways for the prevention or treatment of cancer and chronic human illnesses.
Whole Body Vibration For Osteoporosis: Shaking Up Our Treatment Options
Funder
National Health and Medical Research Council
Funding Amount
$961,017.00
Summary
Our aim is to examine the ability of vibration alone and in combination with osteoporosis drugs to reduce hip fracture in postmenopausal women. In Australia, 1 in 2 women >60yrs, will sustain an osteoporotic fracture. Only drugs notably decrease fracture; however none are entirely effective and some patients don’t respond. Whole body vibration has emerged as a potentially effective therapy. A combination of vibration and drugs may enhance the effects of both and revolutionise treatment.
Why Is The Bone Marrow A “hot-spot” For Myeloma Plasma Cell Metastasis: Are There Gremlins In The System?
Funder
National Health and Medical Research Council
Funding Amount
$651,979.00
Summary
Most cancer patients die because their cancer spreads from a primary site to other tissues in the body. Once escaping the primary site, 70% of all tumours will spread to bone. This raises the question, why is bone a preferred destination for cancer cells? We provide evidence that Gremlin1, made by non-cancer cells within bone, is a key protein that supports cancer growth. This study will examine whether inhibiting Gremlin1 is a potential therapy to inhibit cancer spreading to bone.