The Role Of The Human RECK Protein In Modifying Human Sarcoma Progression Within In Vitro And In Vivo Models
Funder
National Health and Medical Research Council
Funding Amount
$34,878.00
Summary
The protein “RECK” is known to have a controlling effect on cancers by reducing growth, invasion, and blood supply. RECK is present in normal tissues but in bone and soft-tissue tumours (sarcomas), the protein is reduced. This study aims to; correlate RECK levels in sarcoma with patient survival, use gene technology to increase RECK levels in sarcoma cells, and observe the effects on sarcoma invasion and metastasis.
Signalling Through A Bioactive Aggrecan Fragment: What Is The Mechanism?
Funder
National Health and Medical Research Council
Funding Amount
$431,347.00
Summary
Osteoarthritis (OA) affects approximately 20% of Australians. There are no therapies that modify the course of the disease and joint replacement surgery is expensive and invasive. We have discovered that a peptide product of cartilage breakdown (the 32mer) signals cartilage cells to mount an inflammatory and catabolic response. We will determine how the 32mer triggers this response, whether other joint cells are similarly activated and how it can be stopped, with the goal of pursuing new targets ....Osteoarthritis (OA) affects approximately 20% of Australians. There are no therapies that modify the course of the disease and joint replacement surgery is expensive and invasive. We have discovered that a peptide product of cartilage breakdown (the 32mer) signals cartilage cells to mount an inflammatory and catabolic response. We will determine how the 32mer triggers this response, whether other joint cells are similarly activated and how it can be stopped, with the goal of pursuing new targets for therapyRead moreRead less
Platelet Glycoprotein Proteolysis: Novel Mechanisms And Risk Factors
Funder
National Health and Medical Research Council
Funding Amount
$441,473.00
Summary
Platelets are the richest source of amyloid precursor protein (APP) in the body. Platelet ADAM10 regulates both the expression and function of the major platelet collagen receptor GPVI, and protective APP processing. Coagulation protein Factor X has a role in activation of ADAM10. This activation is disrupted in blood that has been treated with direct oral anticoagulant (DOAC) rivaroxaban. This grant will investigate the implications for people taking rivaroxaban on regulation of APP and GPVI.
Platelets are key blood elements that are essential for the prevention of bleeding in response to injury or infection. Overactive or spontaneously active platelets cause thrombosis and blood clot formation. My laboratory has identified new physiological pathways of activation of platelet metalloproteinases, the enzymes that regulate surface levels of the prothrombotic platelet receptors. By understanding this mechanism of receptor regulation, we can uniquely target platelet receptors in people w ....Platelets are key blood elements that are essential for the prevention of bleeding in response to injury or infection. Overactive or spontaneously active platelets cause thrombosis and blood clot formation. My laboratory has identified new physiological pathways of activation of platelet metalloproteinases, the enzymes that regulate surface levels of the prothrombotic platelet receptors. By understanding this mechanism of receptor regulation, we can uniquely target platelet receptors in people with prothrombotic pathologies.Read moreRead less
Defining The Role Of MMP-9-expressing Macrophages In Liver Injury In Chronic Liver Disease
Funder
National Health and Medical Research Council
Funding Amount
$542,028.00
Summary
Defining pathways that lead to fibrosis in chronic liver disease is an urgent priority and unmet need because cirrhosis remains a major cause of death. We will study the development of an additional fibrogenic pathway involving altered liver repair mechanisms, in order to seek ways to restore liver function. New insights arising from this novel research could significantly advance our understanding of how fibrosis develops and lead to new approaches to treat and prevent advanced liver disease.
Humanisation And Pre-clinical Validation Of A Therapeutic Anti-cancer Antibody
Funder
National Health and Medical Research Council
Funding Amount
$699,136.00
Summary
This grant will develop a novel antibody against a protease expressed on cancer cells. Preclinical studies, and antibody humanisation, will be performed. This project will also provide vital information on optimal therapeutic approaches with the antibody that can be ultimately taken into human trials.
Improving Muscular Dystrophy By Targeting The ADAMTS5 Metalloproteinase
Funder
National Health and Medical Research Council
Funding Amount
$658,571.00
Summary
Muscular dystrophy is a devastating childhood disorder. There is no cure and no effective therapy to stop the disease progressing to early death. Our pilot data show that muscular dystrophy in a mouse model is dramatically improved when the Adamts5 gene is inactivated. ADAMTS5 is an enzyme that remodels the extracellular matrix around cells. This suggests that inhibiting ADAMTS5 may be a new way to treat muscular dystrophy. We will test this idea in mice with muscular dystrophy
Antibody-based Inhibition Of ADAM10 As Cancer Immunotherapy
Funder
National Health and Medical Research Council
Funding Amount
$652,788.00
Summary
Despite our advances in understanding the molecular basis of cancer, treatments for metastatic cancers are limited, emphasising an urgent need for strategies targeting several oncogenic pathways. We generated monoclonal antibodies effectively blocking the activity of ADAM10, an oncogenic cell surface protease that activates tumour growth, invasion and metastasis through multiple pathways. Here we describe the strategies that progress these antibodies as lead therapeutics for clinical testing.