Understanding The Mechanisms Of Steroid Resistant Inflammatory Pathways In Mouse Models Of Asthma: Potential New Treatment Approaches
Funder
National Health and Medical Research Council
Funding Amount
$523,694.00
Summary
Steroids are used to treat asthma but some patients are resistant to therapy, and there is no effective treatment. Such patients suffer greater morbidity and mortality, and the heath care cost for clinical management is a significant economic burden. In this project we will obtain a better understanding of the mechanisms that regulate steroid-resistant components of disease, which control inflammation and narrowing of the airway. These studies will be central to the development of new therapies.
Phenotypic And Functional Characterisation Of CD4 T Helper 22 Cells And Their Role In The Regulation Of Chronic Allergic Disease Of The Lung And Skin
Funder
National Health and Medical Research Council
Funding Amount
$714,061.00
Summary
Allergic inflammatory diseases such as asthma and allergic dermatitis are major health problems in our community that lead to poor quality of life. These diseases are induced by activation of immune cells known as T helper (Th) lymphocytes. Recently Th22 cells have been identified in patients with allergic diseases. In this study we will, for the first time, characterise these cells and determine their role in the processes that lead to chronic inflammation in asthma and allergic dermatitis.
Characterising The Pro-inflammatory Role Of IL-36γ/IL-36R In Pathogen-induced Exacerbations Of Asthma And COPD
Funder
National Health and Medical Research Council
Funding Amount
$738,768.00
Summary
Lung infections cause exacerbations in patients with asthma and COPD and these are difficult to treat and can be life-threatening. We have discovered that the cytokine pathway, IL-36?/IL-36R, is linked to the host response to bacterial and viral infections that induce exacerbations in these patients. Our studies will provide new insight into the role IL-36?/IL-36R in infection, disease exacerbation and determine the therapeutic benefit of blocking this pathway.
Mast Cell Proteases Suppress Respiratory Viral Infections And Alleric Inflammation Of The Airways
Funder
National Health and Medical Research Council
Funding Amount
$665,532.00
Summary
Severe RSV infection and asthma accounts for poor quality of life in our community and current treatments have limited effects. Although the factors regulating these disorders are poorly understood, mast cells (MCs) may play important roles. We have shown MC protease-6 protects against viral infection. Here we will identify how MC and their factors are involved in the control of severe respiratory infections and allergic disease of the lung, and identify potential new ways to treat these conditi ....Severe RSV infection and asthma accounts for poor quality of life in our community and current treatments have limited effects. Although the factors regulating these disorders are poorly understood, mast cells (MCs) may play important roles. We have shown MC protease-6 protects against viral infection. Here we will identify how MC and their factors are involved in the control of severe respiratory infections and allergic disease of the lung, and identify potential new ways to treat these conditions.Read moreRead less
Targeting MicroRNA (miRNA) As A Unified Therapeutic Approach To The Treatment Of Asthma And Allergic Inflammation
Funder
National Health and Medical Research Council
Funding Amount
$675,030.00
Summary
Approximately 30% of our community suffers from allergic inflammation (asthma/rhinitis/dermatitis) that results in poor quality of life. The factors regulating these disorders are poorly understood and current treatments only target the symptoms and not the cause of disease. MicroRNA control gene expression and are emerging as potential regulators of inflammation. This project will identify the role of microRNA in the regulation of allergic diseases and their potential as new therapeutic targets ....Approximately 30% of our community suffers from allergic inflammation (asthma/rhinitis/dermatitis) that results in poor quality of life. The factors regulating these disorders are poorly understood and current treatments only target the symptoms and not the cause of disease. MicroRNA control gene expression and are emerging as potential regulators of inflammation. This project will identify the role of microRNA in the regulation of allergic diseases and their potential as new therapeutic targets.Read moreRead less
Fetal Growth Restriction, Low Birth Weight And The Development Of Asthma
Funder
National Health and Medical Research Council
Funding Amount
$397,003.00
Summary
Asthma is a common disease in Australia that causes breathing difficulties. Studies have shown that restricted growth in the womb may be linked to developing asthma in childhood and adulthood. The reason for this isn't clear but we believe that restricted growth may alter the normal development of the baby's airway and lungs. Changes to the normal structure of the lungs leads to a higher risk of developing asthma.
Idiopathic pulmonary fibrosis (IPF) is a fatal disease of unknown cause which is unresponsive to current therapy. This study builds on recent work by this group highlighting the importance of a cell signalling molecule called STAT3 in the development of this disease. In particular, two cell types that utilise STAT3 signalling, epithelial cells and B cells, will be examined to see if blocking their STAT3 responses could be a novel therapeutic approach.
Hydrostatic Pressure Distributions In Peri-pharyngeal Tissues : Impact On Upper Airway Patency
Funder
National Health and Medical Research Council
Funding Amount
$508,935.00
Summary
The obstructive sleep apnoea hypopnoea syndrome (OSAHS) refers to a condition in which throat blockage occurs during sleep leading to breathing difficulties, including cessation of breathing for short periods of time. OSAHS affects both men and women but is amongst the commonest of chronic disorders of adult males, occurring in ~4% of men over the age of 45 years. In the proposed studies we will develop a computer model of the function of the throat during breathing. A particular focus of our mo ....The obstructive sleep apnoea hypopnoea syndrome (OSAHS) refers to a condition in which throat blockage occurs during sleep leading to breathing difficulties, including cessation of breathing for short periods of time. OSAHS affects both men and women but is amongst the commonest of chronic disorders of adult males, occurring in ~4% of men over the age of 45 years. In the proposed studies we will develop a computer model of the function of the throat during breathing. A particular focus of our model will be the influence of the properties of the tissue that form the walls of the throat. Our goal is to construct a computer model that will be useful in identifying specific features of throat function that make people susceptble to the development of OSAHS. In this manner we hope to provide a tool that can be used to develop new approaches to the treatment and prevention of OSAHS.Read moreRead less
Interleukin-17A Promotes Cigarette Smoke-induced Lung Inflammation And Damage
Funder
National Health and Medical Research Council
Funding Amount
$650,590.00
Summary
Emphysema is a major global health problem and has been predicted to become the third largest cause of death in the world by 2020. Cigarette smoking is the major cause of emphysema and accounts for more than 95% of cases in industrialized countries. Cigarette smoke triggers cells in the lung to release substances which cause inflammation and "eat away" lung tissue. The aim of this project is to identify therapies to prevent and treat emphysema.
Altered Gp130-mediated Signalling In The Regulation Of Pulmonary Fibrosis
Funder
National Health and Medical Research Council
Funding Amount
$373,956.00
Summary
Pulmonary fibrosis is a chronic diffuse interstitial lung disease often of unknown cause, characterised pathologically by inflammation and fibrosis of the lung tissue. The prognosis is poor with a 50% mortality at five years after diagnosis and considerable morbidity during those years. Previous investigations have documented the role for inflammation in the development of pulmonary fibrosis and current therapeutic strategies are aimed at suppressing the inflammation using anti- inflammatory dru ....Pulmonary fibrosis is a chronic diffuse interstitial lung disease often of unknown cause, characterised pathologically by inflammation and fibrosis of the lung tissue. The prognosis is poor with a 50% mortality at five years after diagnosis and considerable morbidity during those years. Previous investigations have documented the role for inflammation in the development of pulmonary fibrosis and current therapeutic strategies are aimed at suppressing the inflammation using anti- inflammatory drugs, almost exclusively steroids. The effectiveness of steroids is variable although generally poor and can be associated with significant side effects suggesting that other approaches need to be considered. Data generated over the past decade also have established the concept that the molecular processes underlying the development of fibrosis may represent a new opportunity for therapeutic intervention. This project will build on previous studies examining the effects of a family of molecules called cytokines that signal through gp130 as critical determinants of disease susceptibility and progression. gp 130 is a shared component in the receptor complexes for IL-6 family cytokines and can signal down two major pathways. We have shown that the development of lung fibrosis depends on which specific signalling pathway is used. This study will determine how fibrosis is controlled by these pathways. Our data raises the possibility of developing pharmacological manipulators of gp130 signalling pathways that would suppress fibrosis but leave normal cellular defense mechanisms necessary for host defense in the lung intact.Read moreRead less