Epithelial-Mesenchymal Cell Communication; Towards New Therapeutic Targets For Fibrosis
Funder
National Health and Medical Research Council
Funding Amount
$794,596.00
Summary
Fibrosis causes disability and death with millions of people affected each year. Current treatments are limited and there is a need to better understand the changes that drive fibrosis. In this study we will investigate how cells communicate to initiate and drive fibrosis. Using readily available drugs we will test new ways to alter cell communication to stop the disease and thus, develop a common and effective therapy that will change the future for people living with fibrosis.
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.
The Link Between Vitamin D Deficiency And Chronic Lung Disease Is Due To Increased Airway Smooth Muscle
Funder
National Health and Medical Research Council
Funding Amount
$644,067.00
Summary
Vitamin D deficiency is a global public health problem. It is becoming increasingly evident that vitamin D deficiency increases the severity of chronic lung disease. In this study we propose to examine a mechanism that we think clearly explains this association. These studies are critical to understanding how deficiencies in key nutrients can impact on chronic lung disease and will provide the data necessary to guide public health policy to reduce the burden of disease in the community.
Targeting An Epigenetic Silencing Pathway To Treat Allergic Asthma
Funder
National Health and Medical Research Council
Funding Amount
$318,768.00
Summary
Asthma affects around 11% of the Australian population and costs the health care system around $28 billion. Unfortunately there is still no cure and treatments have not changed for decades. This project aims to discover new drugs to treat asthma by re-wiring the cells of the immune system which cause the disease.
Regional Mechanisms Of Ventilator Induced Lung Injury: Insights From Dynamic Lung Imaging
Funder
National Health and Medical Research Council
Funding Amount
$623,323.00
Summary
Mortality rates due to acute respiratory distress syndrome (ARDS) are high (>30%). While ARDS requires mechanical ventilation as a lifesaving intervention, it is clear that mechanical ventilation itself can contribute to the high mortality rates. We will use a new lung imaging technology (CTXV) to visualize the damage that occurs to the lung as a result of mechanical ventilation in order to design better ventilation strategies and reduce mortality rates in these critically ill patients.
Targeting Remodelling In Chronic Obstructive Pulmonary Disease (COPD), Chronic Asthma And Idiopathic Pulmonary Fibrosis (IPF)
Funder
National Health and Medical Research Council
Funding Amount
$386,634.00
Summary
Lung diseases (emphysema, asthma & pulmonary fibrosis) are major burdens on Australian community and economy. Airway remodelling/wounding is a key feature of all these diseases. Patients experience severe breathlessness seriously impacting quality of life and frequently leading to death. We will assess the potential of new targets (including IL-33), & therapy in suppressing wounding in experimental models. This may lead to a new treatment to reverse or prevent lung diseases.
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
Restoring Skeletal Muscle In An Experimental Model Of COPD By Targeting The IGF-1-myostatin-macrophage Axis
Funder
National Health and Medical Research Council
Funding Amount
$508,183.00
Summary
Most people think that the serious disabilities of COPD (emphysema) patients follows damage to their lungs but wasted muscles may be even more important. We can not regrow lung but we have found a way that might help regrow muscle. We plan to use stem cells to make one of the body's own cells called 'macrophages' and genetically engineer these cells to help deliver healing proteins directly into the muscle. Making muscle stronger will help COPD patients live longer and improve quality of life.
DEFINING SUBPOPULATIONS OF PATHOGENIC MACROPHAGES UNDERLYING LUNG DISEASES
Funder
National Health and Medical Research Council
Funding Amount
$640,496.00
Summary
Chronic obstructive pulmonary disease (COPD) is a serious lung disease that afflicts over 1 million people in Australia and adenocarcinoma is a common fatal lung cancer; both are typically caused by cigarette smoking, and macrophage-rich inflammation is a hallmark feature. Macrophages can destroy lung tissue and promote cancer development. Herein we will identify and profile macrophage subpopulations that are associated with lung inflammation and cancer to identify therapeutic targets that may y ....Chronic obstructive pulmonary disease (COPD) is a serious lung disease that afflicts over 1 million people in Australia and adenocarcinoma is a common fatal lung cancer; both are typically caused by cigarette smoking, and macrophage-rich inflammation is a hallmark feature. Macrophages can destroy lung tissue and promote cancer development. Herein we will identify and profile macrophage subpopulations that are associated with lung inflammation and cancer to identify therapeutic targets that may yield novel intervention strategies.Read moreRead less