Aberrant Signalling Through Gp130 In The Pathogenesis Of Fibrotic Lung Diseases
Funder
National Health and Medical Research Council
Funding Amount
$456,500.00
Summary
Pulmonary fibrosis is a chronic diffuse interstitial lung disease 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. Data generated over the past deca ....Pulmonary fibrosis is a chronic diffuse interstitial lung disease 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. Data generated over the past decade also have established the concept that the molecular processes underlying the fibrogenesis component may represent a new opportunity for therapeutic intervention. Attempts to treat fibrosis have for the most part consisted of anti- inflammatory drugs, almost exclusively steroids. The effectiveness of steroids is variable and can be associated with significant side effects. This project will examine 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 (IL-6, IL-11, LIF, OSM) which are important regulators of both the phenotype and proliferation of fibroblasts in health and in response to injury. 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
Airway fibrosis or scaring causes significant morbidity in both chronic obstructive pulmonary disease (COPD) and asthma . These diseases affect 10-15% of the population, and cost the health system $1.15 billion per year. Airway fibrosis is not decreased by the current therapeutics used to treat COPD and asthma, and as such there is a pressing need to develop therapeutics to specifically treat airway fibrosis. Dr Brian Oliver has partnered with Pharmaxis to develop new therapeutics to specificall ....Airway fibrosis or scaring causes significant morbidity in both chronic obstructive pulmonary disease (COPD) and asthma . These diseases affect 10-15% of the population, and cost the health system $1.15 billion per year. Airway fibrosis is not decreased by the current therapeutics used to treat COPD and asthma, and as such there is a pressing need to develop therapeutics to specifically treat airway fibrosis. Dr Brian Oliver has partnered with Pharmaxis to develop new therapeutics to specifically treat fibrosisRead moreRead less
Dr Reid is a respiratory physician determining the relationships between bacterial pathogen behaviour and the host immune response in Cystic Fibrosis. The aim of his research is to use observations made in the clinical setting to develop novel therapeutics and identification of biomarkers that will be employed to pre-empt and better treat clinical disease with the ultimate aim of improving length and quality of life.
Fibroblast Senescence As A Driver Of Pulmonary Fibrosis
Funder
National Health and Medical Research Council
Funding Amount
$845,611.00
Summary
Idiopathic pulmonary fibrosis (IPF) has no cure. Currently we think that IPF develops like normal wound healing, but the normal “braking” mechanisms in the myofibroblasts (the cells that produce the connective tissue) don’t work, such that too much connective tissue is produced and oxygen transfer to the blood is stopped. We have identified a protein we think stops, the myofibroblasts from dying. Reducing the activation of this protein should return the myofibroblasts function to normal.
Evolution Of Airway Function And Inflammation In Early Cystic Fibrosis Lung Disease
Funder
National Health and Medical Research Council
Funding Amount
$494,447.00
Summary
Our goal is to evaluate if lung function can identify the onset of early lung disease in infants with cystic fibrosis (CF). We aim to evaluate: - Changes in lung function in infants with CF. - Associations between lung function and lung inflammation and infection. - Links between infant lung function and disease severity at 2 years of age. The long term aims are to determine how useful lung function will be in trials of novel treatments for the early treatment of CF.
Early Life Exposures And Chronic Disease: Mechanisms And Preventative Strategies
Funder
National Health and Medical Research Council
Funding Amount
$851,980.00
Summary
The world is facing an epidemic of chronic disease and adverse environmental exposures in early life are partly responsible. One reason why we have not been able to do more to prevent this is the lack of appropriate methods for measuring environmental exposures during pregnancy and infancy. My research will develop and validate methods for measuring exposures early life and the health consequences of these exposures with the aim of developing preventative interventions
Understanding The Mechanisms Underlying Airway Remodelling
Funder
National Health and Medical Research Council
Funding Amount
$451,716.00
Summary
Changes in the structure of the lung contribute to the development of disease, but are not responsive to our current therapies. I have found two key structural proteins that are altered in asthma. This research will characterise the regulation and role of these proteins in the disease process. In addition, it will determine if these proteins also contribute to the development of other serious fibrotic diseases, for which there are no current treatments.
Centre For Research Excellence In Pulmonary Fibrosis
Funder
National Health and Medical Research Council
Funding Amount
$2,498,607.00
Summary
The Centre for Research excellence in Pulmonary Fibrosis (CRE-PF) aims to develop a sustainable nation-wide network, consisting of world recognized experts. The group will enable an integrative approach to solving PF through a layered strategy extending from molecules germane to disease pathogenesis, to human studies. With this approach the CRE-PF will set a new paradigm for synergy between academia, health care, health policy and the public, placing Australia at the forefront of innovation.
The Importance Of Neutrophil Plasticity In Early Cystic Fibrosis Lung Disease
Funder
National Health and Medical Research Council
Funding Amount
$318,768.00
Summary
Lung disease is a lifelong problem for people with cystic fibrosis (CF). Blood immune cells called neutrophils swarm the lung and cause ongoing damage. No treatments exist because how CF lungs talk to neutrophils is poorly understood. I will apply new skills from an international neutrophil expert to study samples from AREST CF, a world leading CF research group. This unique combination will recreate the early CF lung in the laboratory, testing triggers of CF lung disease and potential drugs.