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Research Topic : Statistical models for cancer and cardiovascular disease
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  • Funded Activity

    Analysing Genetic And Environmental Risk Factors And Their Interactions For Common Cancers And Cardiovascular Disease

    Funder
    National Health and Medical Research Council
    Funding Amount
    $129,937.00
    Summary
    The statistical models for analysing cancer and cardiovascular risk factor family data are important for understanding the genetic and environmental aetiology of these diseases, but complicated by the different levels of correlations between relatives in a family. The conventional assumption of independence in observations is invalid in these situations. We intend to develop, test, implement and distribute a comprehensive suite of new statistical methods designed specifically to assistant molecu .... The statistical models for analysing cancer and cardiovascular risk factor family data are important for understanding the genetic and environmental aetiology of these diseases, but complicated by the different levels of correlations between relatives in a family. The conventional assumption of independence in observations is invalid in these situations. We intend to develop, test, implement and distribute a comprehensive suite of new statistical methods designed specifically to assistant molecular geneticists and genetic epidemiologists undertake informative and meaningful analyses of the measured and latent genetic and environmental risk factors and their possible interactions. The two associate investigators, Prof John Hopper and Prof Stephen Harrap, will bring their respective genetic epidemiological and biometric statistical expertise and their prestigious family data resources to this project. With the suite of flexible statistical models and analyses, we will further our knowledge about genetic and environmental risk factors and their interactions of common cancers and major gene effects for cardiovascular phenotypes. Simulation studies will help us understand some phenomena accounted in the research but cannot be replicated in reality and assess the efficiency of the statistical methods and credibility of our analysis results independently. Statistical programs developed in this project can also be used in other genetic and epidemiological studies (e.g. diabetes, epilepsy) where such high-level statistical tools are not yet available.
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    Strategies For Communicable Disease Control In Aborigin Al Australians

    Funder
    National Health and Medical Research Council
    Funding Amount
    $133,926.00
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    Funded Activity

    Is NADPH Oxidase The Trigger For Accelerated Atherosclerosis Caused By Bacteria?

    Funder
    National Health and Medical Research Council
    Funding Amount
    $465,210.00
    Summary
    Cardiovascular disease is the leading cause of death and morbidity world-wide. However, its incidence is not fully explained by the presence of conventional risk factors, such as high cholesterol, hypertension, diabetes and cigarette smoking. Steadily growing evidence indicates that bacterial infection, particularly by Chlamydia pneumoniae and Helicobacter pylori, is also strongly linked to atherosclerotic lesion formation and increased risk of a cardiovascular event. This project will investiga .... Cardiovascular disease is the leading cause of death and morbidity world-wide. However, its incidence is not fully explained by the presence of conventional risk factors, such as high cholesterol, hypertension, diabetes and cigarette smoking. Steadily growing evidence indicates that bacterial infection, particularly by Chlamydia pneumoniae and Helicobacter pylori, is also strongly linked to atherosclerotic lesion formation and increased risk of a cardiovascular event. This project will investigate a new aspect to the body s defence against bacterial infection which involves production of oxygen radicals by the blood vessel wall. We propose that although this response of the artery to bacteria in the blood is beneficial in the short term, it inadverently initiates a chronic inflammatory process that ultimately accelerates development of artery disease. If this is the case, the oxygen radical production by the enzyme, NADPH oxidase, in the artery wall may represent the missing link between bacterial infection and atherosclerosis. We will therefore firstly test whether two bacteria, Chlamydia pneumoniae and Helicobacter pylori, can acutely induce artery inflammation in this way. We will then perform definitive studies to test whether mice infected with these bacteria develop accelerated atherosclerosis, and if so, whether this effect is dependent on NADPH oxidase activity in the artery wall. Finally, we will test the efficacy and importance of timing of antibiotic therapy to prevent atherosclerotic lesion formation.
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    Regulator Of G-protein Signalling-5: A Key Modulator Of Vascular Maturation And The

    Funder
    National Health and Medical Research Council
    Funding Amount
    $548,396.00
    Summary
    Tumours progressively grow in part because they escape destruction by the immune system. New blood vessels grow inside tumours by a process called angiogenesis, which in turn stops disease-fighting cells in their tracks. However, we have now discovered that it is possible to reverse angiogenesis by normalising the blood vessels. This effectively means the barriers are broken down and the tumour can be opened to the immune system or cancer fighting drugs. Furthermore, we have identified a protein .... Tumours progressively grow in part because they escape destruction by the immune system. New blood vessels grow inside tumours by a process called angiogenesis, which in turn stops disease-fighting cells in their tracks. However, we have now discovered that it is possible to reverse angiogenesis by normalising the blood vessels. This effectively means the barriers are broken down and the tumour can be opened to the immune system or cancer fighting drugs. Furthermore, we have identified a protein which appears to be very important for normalisation, a process which is currently not well understood. This proposal continues our pioneering work on vessel normalisation and will use models of highest clinical relevance to study the dynamics of vessel remodelling in tumours. Our approach is different to current angiogenesis research which simply tries to block or destroy the blood vessels that feed tumours. We expect our findings to lead to highly specific and effective anti-tumour therapies. Moreover, vessel growth in tumours has striking parallels to other vascular processes in the body, which have important implications for major and common human diseases such as high blood pressure and atherosclerosis. We now have the tools to study these processes and their abnormalities in our newly established disease model. By gaining insight into these disorders we will be able to develop novel approaches to stop disease progression.
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    Healthy Heart, Healthy Brain - Using Genetic Data To Investigate The Causal Relationship Between Cardiovascular And Neurodegenerative Disease

    Funder
    National Health and Medical Research Council
    Funding Amount
    $191,261.00
    Summary
    There is growing evidence supporting a strong association between cardiovascular disease (CVD) with neurodegenerative disease. However, evidence from observational studies has been inconsistent. This project will use genetic data to investigate this link. The project outcomes may point to new avenues for research and prevention, whereby lifestyle modifications pharmaceutical interventions which decrease CVD might also hold promise for reducing the burden of neurodegenerative disease.
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    Funded Activity

    Statistical Methods For The Analysis Of Trends In Coronary Heart Disease

    Funder
    National Health and Medical Research Council
    Funding Amount
    $112,747.00
    Summary
    Coronary heart disease is a leading cause of mortality, morbidity and medical costs in Australia. During the 1950's and 1960's, rates of coronary disease increased rapidly, then in the late 1960's they started to decline. This decrease has continued steadily for 30 years. While some other westernised countries have had this same experience, in Eastern Europe and in many developing countries coronary disease is increasing. There is a huge amount of evidence from experimental studies in animal and .... Coronary heart disease is a leading cause of mortality, morbidity and medical costs in Australia. During the 1950's and 1960's, rates of coronary disease increased rapidly, then in the late 1960's they started to decline. This decrease has continued steadily for 30 years. While some other westernised countries have had this same experience, in Eastern Europe and in many developing countries coronary disease is increasing. There is a huge amount of evidence from experimental studies in animal and human subjects and population studies in many countries that the major determinants of coronary disease are high blood pressure, cigarette smoking and high cholesterol (and other lipids) as well as dietary factors, obesity and physical inactivity. Recently several large multicentre studies have found unexpectedly weaker associations between heart risk factors and disease rates. It is hypothesised that this is due to inappropriate analyses in which data from populations at different stages of the coronary epidemic have been combined. The aim of this study is to develop improved statistical methodology to help understand recent findings from large scale studies, such as the World Health Organization's MONICA Project, the US ARIC study and the Seven Countries study. It will provide new theoretical results and statistical software for their implementation. From a public health perspective the most important outcome will be clarification of recent apparently anomalous findings about the importance of established risk factors and effective treatments in reducing coronary disease at the population level.
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    Funded Activity

    Use Of The Norfolk Island Genetic Isolate For Disease Gene Mapping

    Funder
    National Health and Medical Research Council
    Funding Amount
    $978,500.00
    Summary
    This gene mapping study will use a unique founder effect population to investigate two major public health disorders. We aim to identify genes that play a role in migraine and in cardiovascular disease, using a population from Norfolk Island. The Norfolk Island community is a population of ~1200 permanent residents, the majority of whom are direct descendents of 18th century English Bounty mutineers and Polynesian women. We will undertake a full genome scan to identify migraine gene loci and QTL .... This gene mapping study will use a unique founder effect population to investigate two major public health disorders. We aim to identify genes that play a role in migraine and in cardiovascular disease, using a population from Norfolk Island. The Norfolk Island community is a population of ~1200 permanent residents, the majority of whom are direct descendents of 18th century English Bounty mutineers and Polynesian women. We will undertake a full genome scan to identify migraine gene loci and QTL that influence cardiovascular disease using samples from this population isolate.
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    Funded Activity

    ARC Future Fellowships - Grant ID: FT100100109

    Funder
    Australian Research Council
    Funding Amount
    $669,992.00
    Summary
    Improved theory and practice in econometric modelling of nonlinear spatial time series. Modern Australia faces many challenges in economic and global climate changes, which require advanced statistical technologies in modeling and forecasting of econometric spatial time series data. This project will provide flexible models and methods that enable practitioners to more accurately measure and manage economic and climatic risks.
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    Funded Activity

    The Role Of The TGF-b Superfamily Cytokine MIC-1 In The Pathogenesis Of Atherosclerosis

    Funder
    National Health and Medical Research Council
    Funding Amount
    $348,950.00
    Summary
    MIC-1 is a protein first cloned and characterised by our research group. It belongs to the TGF beta protein superfamily which is very important in development, cancer, wound - fracture healing and inflammation. The aim of this project was to start to gain an understanding of the role of this protein, both in normal biological processes (especially pregnancy) and in disease. MIC-1 is present in the blood of all individuals and high levels are associated with an increased risk of heart attacks and .... MIC-1 is a protein first cloned and characterised by our research group. It belongs to the TGF beta protein superfamily which is very important in development, cancer, wound - fracture healing and inflammation. The aim of this project was to start to gain an understanding of the role of this protein, both in normal biological processes (especially pregnancy) and in disease. MIC-1 is present in the blood of all individuals and high levels are associated with an increased risk of heart attacks and strokes. In this study we wish to use animal models, in which the gene for MIC-1 has either been deleted or enhanced, to determine whether MIIC-1 plays a direct role in these diseases.
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    Funded Activity

    Regulator Of G Protein Signalling-5 Loss And Gain Of Function In Vivo

    Funder
    National Health and Medical Research Council
    Funding Amount
    $625,428.00
    Summary
    Cancer and cardiovascular diseases are amongst the largest causes of morbidity and mortality in Western populations. We have identified a molecule, called Regulator of G protein signalling 5 (RGS5), which is involved in vessel remodelling in both diseases. This molecule is a prime candidate for drug development. We will study the precise role of RGS5 in sophisticated preclinical models which will create future opportunities for urgent therapy.
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