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  • Funded Activity

    The Relationship Between Vascular Remodelling And Mast Cells In Chronic Asthma

    Funder
    National Health and Medical Research Council
    Funding Amount
    $353,253.00
    Summary
    It is known that the airwalls of asthmatics have increased numbers of small blood vessels which can contribute to poor lung function in asthma. The proposed research uses a novel sheep model for chronic asthma to investigate the progressive changes to the blood vessels in the airway walls of asthmatic lungs. The information gained from our sheep model will assist the understanding of blood vessel growth and thus ulitmately help in devising new strategies to treat the effects of asthma.
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    Funded Activity

    Practitioner Fellowship - Grant ID:632910

    Funder
    National Health and Medical Research Council
    Funding Amount
    $317,308.00
    Summary
    A-Prof Wheatley is a respiratory and sleep disorders physician investigating the pathogenesis, health consequences and management of sleep breathing disorders, including sleep apnoea and snoring.
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    Funded Activity

    The Role Of Snoring Vibrations In The Pathogenesis Of Early Carotid Artery Atherosclerosis

    Funder
    National Health and Medical Research Council
    Funding Amount
    $593,833.00
    Summary
    Habitual snoring is a very common problem in the adult population, with a prevalence of between 20-40%. Increasingly it is now recognised that snoring may be an independent risk factor for the development of stroke. In this proposal, we will explore the hypothesis that chronic snoring transmits a pressure wave through the tissues of the neck to the carotid artery which may damage the artery wall and subsequently lead to stroke. This may lead to new strategies to treat habitual snoring.
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    Funded Activity

    THE VASCULAR CONSEQUENCES OF SNORING AND OBSTRUCTIVE SLEEP APNOEA

    Funder
    National Health and Medical Research Council
    Funding Amount
    $476,052.00
    Summary
    Snoring refers to a condition where the throat narrows significantly during sleep, and allows the soft tissues which surround this part of the airway to vibrate and create the typical snoring noise. Habitual snoring is a very common problem in the adult population, with a prevalence of between 20-40%. More severe forms of snoring are associated with the obstructive sleep apnoea syndrome, which is a condition in which the throat completely blocks behind the tongue and palate during sleep leading .... Snoring refers to a condition where the throat narrows significantly during sleep, and allows the soft tissues which surround this part of the airway to vibrate and create the typical snoring noise. Habitual snoring is a very common problem in the adult population, with a prevalence of between 20-40%. More severe forms of snoring are associated with the obstructive sleep apnoea syndrome, which is a condition in which the throat completely blocks behind the tongue and palate during sleep leading to cessation of breathing for short periods of time. Sleep apnoea is among the commonest chronic disorders of adult males occurring in 5% of men over the age of 45 years. Increasingly, it is now recognised that snoring, without sleep apnoea, may be an independent risk factor for the development of both of these very common and significant medical disorders. However, there have been no studies exploring the mechanisms by which snoring might contribute to the development of stroke and hypertension. In this proposal, we will explore the hypothesis that chronic snoring transmits a pressure wave through the tissues of the neck to the carotid artery which is the main blood supply to the brain. We propose that the chronic vibration of this artery leads to disease such as atherosclerosis and hypertension. Our studies will help to prove that this is a common mechanism whereby both snoring and sleep apnoea may contribute to the development of important vascular diseases. Studies will also establish the prevalence of carotid atherosclerosis in snorers (with and without OSA), and the prevalence of habitual snoring and OSA in patients at risk of developoing completed stroke. The recognition of snoring as an independent risk factor for vascular disease will clearly have important and wide ranging implications for the future management of snoring in the prevention of stroke and hypertension.
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    Funded Activity

    The Central Role Of Connective Tissue Growth Factor In Remodelling Of Asthmatic Airways

    Funder
    National Health and Medical Research Council
    Funding Amount
    $689,019.00
    Summary
    In the asthmatic airway an increase in the number of blood vessels can affect an asthmatic's ability to breathe. We have recently found that growth factors which can promote vessel growth are increased in the airways of asthmatics. We want to understand how these growth factors act together to possibly control the blood vessels and how their behaviour is different in the asthmatic airways compared to the nonasthmatic airways.
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    Funded Activity

    Practitioner Fellowship - Grant ID:453488

    Funder
    National Health and Medical Research Council
    Funding Amount
    $420,541.00
    Summary
    I am a pulmonary physician-gene therapist persuing new therapies for pulmonary vascular disease, lung cancer and mesothelioma, COPD and lung transplant rejection
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    Funded Activity

    Serum Mesothelin-related Protein As An Early Marker Of Mesothelioma

    Funder
    National Health and Medical Research Council
    Funding Amount
    $354,750.00
    Summary
    The deadly asbestos-induced cancer mesothelioma is continuing to kill tens of thousands of individuals per year and its incidence is increasing. It is expected to cost communities hundreds of billions of dollars in compensation. This disease is usually already quite advanced by the time a patients presents to a doctor with symptoms so we have been working on methods of early detection. This project studies a new, exciting method of diagnosis using blood levels of a molecule called 'SMRP'. Late l .... The deadly asbestos-induced cancer mesothelioma is continuing to kill tens of thousands of individuals per year and its incidence is increasing. It is expected to cost communities hundreds of billions of dollars in compensation. This disease is usually already quite advanced by the time a patients presents to a doctor with symptoms so we have been working on methods of early detection. This project studies a new, exciting method of diagnosis using blood levels of a molecule called 'SMRP'. Late last year we published a paper in the prestigious journal Lancet showing that SMRP was a good test to help diagnose mesothelioma and this became a lead news item around the world because of widespread concern about this disease. In those studies we found strong clues that this test was very sensitive and could detect mesothelioma a year or so before a patient develops symptoms. In this grant we will evaluate whether this test could be useful for screening asbestos-exposed individuals for early detection of this cancer. We will also study ways of improving the test using laboratory methods. This would provide a foundation for studies aimed at determining if early treatment could improve patient survival.
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    Funded Activity

    Diagnostic Markers For Malignant Mesothelioma And Other Respiratory Diseases

    Funder
    National Health and Medical Research Council
    Funding Amount
    $467,315.00
    Summary
    The deadly asbestos-induced cancer mesothelioma is continuing to kill tens of thousands of individuals per year. We have been working on improving the tests available to detect this cancer and to follow the course of the disease with the aim of reducing patients' anxiety and health-care costs.
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    Funded Activity

    Investigatin The Causes Of Failed Efferocytosis In COPD-emphysema With A View To Identifying Novel Theraputic Targets

    Funder
    National Health and Medical Research Council
    Funding Amount
    $380,558.00
    Summary
    COPD is a leading cause of death. Smoking is the major cause of COPD and many sufferers are left with permanent damage and need ongoing treatment even after smoking cessation. Current treatments for COPD generally have limited efficacy. The project will identify the reason for the large number of dying cells and defective clearance of these cells that we have identified in the airways in COPD and study novel treatments that we hope will improve the health and well being of those with COPD.
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    Funded Activity

    Long-lasting Correction Of The Basic Defect In Cystic Fibrosis

    Funder
    National Health and Medical Research Council
    Funding Amount
    $458,500.00
    Summary
    The airway disease caused by the genetic disease cystic fibrosis (CF) is not yet preventable. Current treatments can only limit the gradually-increasing lung disease and is costly. Our new gene therapy technique introduces a correcting gene into affected airway cells, and it has already worked in the first tests in mice bred with CF. Airways in mice are used to test whether the effect is reliable, effective, and lasts long enough to be useful. The gene is introduced into the airway using special .... The airway disease caused by the genetic disease cystic fibrosis (CF) is not yet preventable. Current treatments can only limit the gradually-increasing lung disease and is costly. Our new gene therapy technique introduces a correcting gene into affected airway cells, and it has already worked in the first tests in mice bred with CF. Airways in mice are used to test whether the effect is reliable, effective, and lasts long enough to be useful. The gene is introduced into the airway using special virus delivery-particles, after conditioning the airway to make it receptive to the particles. The method works in normal mice and in CF mice; it gives long lasting gene transfer from a single dose and seems to affect all airway cell types. The gene transfer may also be occurring in airway stem cells, i.e. the mother cells from which grow all the cells of the airway surface. Until now, no-one else has been able to produce prolonged gene transfer in this way, nor arrange gene transfer into stem cells in live airways. There are now a number of things that we must investigate before we could conduct safety and effectiveness trials in larger animals, or consider moving into clinical trials in humans. We need to understand exactly how our conditioning agent works and is it safe; measure how long the gene correction can last actually in our animals; decide if we can we re-dose animals (if needed) without losing effectiveness because of inflammation or immune responses that might occur; and decide how important the airway stem cells are in producing the length of the gene transfer. Because it has been difficult to measure gene correction in CF airways, we will also test new ways we have developed to measure how well the gene correction works in CF airways. The findings of this project will allow us to develop our method to where we can test it in larger animals, to provide a strong, long-lasting gene correction that will be safe for testing in human clinical trials.
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