Molecular And Genotypic Risk Factors For Abdominal Aortic Aneurysms
Funder
National Health and Medical Research Council
Funding Amount
$221,750.00
Summary
An Abdominal Aortic Aneurysms (AAA) is a dilatation of the main abdominal artery. This is an asymptomatic condition which may cause sudden death due to rupture of the AAA once it reaches a certain size (usually over 5cm in diameter) Between 1996 and 1998, 12,000 men aged 65-79 attended the Western Australian Abdominal Aortic Aneurysm screening study. The main aim of the study is to assess the influence of screening on mortality from AAA. Since 1997, approximately 90 men with large AAA have had e ....An Abdominal Aortic Aneurysms (AAA) is a dilatation of the main abdominal artery. This is an asymptomatic condition which may cause sudden death due to rupture of the AAA once it reaches a certain size (usually over 5cm in diameter) Between 1996 and 1998, 12,000 men aged 65-79 attended the Western Australian Abdominal Aortic Aneurysm screening study. The main aim of the study is to assess the influence of screening on mortality from AAA. Since 1997, approximately 90 men with large AAA have had elective surgical repair of AAA and 700 men with small AAA (aortic diameter 3-5 cm) have participated in the follow-up study involving 6-12 monthly ultrasound scans. The aim of the follow-up study is to assess rates of and risk factors for expansion of screen-detected AAA. The cause of AAA is unclear but appears to be due to a combination of environmental (eg smoking) and genetic influences. It is unknowm which genes might be involved. The current grant application seeks funding to initiate the study of possible genes associated with AAA . Blood samples from which DNA (genetic material) can be extracted have already been obtained from 650 men with AAA. Men without AAA are currently being reviewed as part of another study and it will be possible to obtain similar DNA samples these men. Patterns of gene polymorphisms (common minor mutations) in men with AAA will be compared with those without AAA.Read moreRead less
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