Genetic Approaches To Understand How Imbalanced Cytokine Signalling Drives The Pathogenesis Of Emphysema
Funder
National Health and Medical Research Council
Funding Amount
$519,715.00
Summary
Emphysema is a major component of Chronic Obstructive Pulmonary Disease (COPD), the fifth leading cause of death in Australia for which there is no effective treatment. We have discovered a specific mutation in a gene called gp130 that results in the formation of emphysema in mice. This finding allows us to understand the exact mechanisms by which this mutation causes emphysema, and therefore has the potential to uncover new strategies to design novel therapies against emphysema in humans.
Elucidating The Role And Potential For Therapeutic Targeting Of TLR7 In Emphysema And COPD
Funder
National Health and Medical Research Council
Funding Amount
$925,780.00
Summary
Emphysema is a major cause of illness and death and there are no effective treatments. It is caused by smoking that damages the airways and air sacs but how this occurs is not well understood. We have found that a new factor, called Toll-like receptor 7, is involved in emphysema. In this study we will now characterise its roles in this disease, work out how it induces emphysema and test new inhibitors (antibodies) that we have developed as treatments.
Identification And Therapeutic Modulation Of Sphingolipids As Novel Lung Macrophage-targeted Treatments For COPD/emphysema
Funder
National Health and Medical Research Council
Funding Amount
$694,704.00
Summary
COPD/emphysema is predicted to be the third leading cause of death woldwide by 2010. We have shown defective lung macrophage function in COPD and have shown that we can modify the macrophage function with novel therapies. We are now investigating a specific “sphingosine” pathway to see if it can provide us with more specific information. We aim to provide a better, more specific, adjunct treatment for the disease.
COPD is a smoking-related airways disease that costs the Australian community over $8.8 billion/yr. It is predicted to become the third most common cause of death in the world by the year 2020 and is linked to an increased risk of lung cancer. There are no effective treatments for COPD. I have been working with a number of anti-inflammatory treatments in a smoking mouse model and will extend my research to see if these treatments can be optimised to treat COPD.
The Molecular Basis By Which The Interleukin-6 Cytokine Promotes Emphysema
Funder
National Health and Medical Research Council
Funding Amount
$659,457.00
Summary
Interleukin 6 (IL-6) is a potent immuno-modulatory cytokine that is commonly elevated in emphysema, the 5th leading cause of death in Australia. To understand the role of IL-6 in emphysema, we aim to demonstrate here by using a unique mouse model for IL-6-driven emphysema and clinical biopsies from emphysema patients, that IL-6 uses an alternative signalling mechanism in emphysema termed trans-signalling. Therefore this project could provide novel therapeutic targets for emphysema.
Novel Role Of Inflammasomes In The Molecular Pathogenesis Of Emphysema
Funder
National Health and Medical Research Council
Funding Amount
$764,462.00
Summary
Emphysema is a chronic lung disease that is caused by dysregulation of the immune system, leading to inflammation and destruction of lung tissue. Although emphysema is associated with cigarette smoking, the key components of the immune system which promote emphysema remain ill-defined. Using elaborate mouse models for emphysema, together with biopsies from emphysema patients, our aim is to reveal the role of a protein complex in the immune system called the inflammasome in driving emphysema.
Deregulated Cytokine Signalling As A Molecular Bridge Linking The Pathogenesis Of Emphysema To Lung Cancer.
Funder
National Health and Medical Research Council
Funding Amount
$524,820.00
Summary
Lung cancer is the most lethal form of cancer in Australia and worldwide. Although smokers with emphysema are at an increased risk of developing lung cancer, it is becoming apparent that emphysema can predispose to lung cancer independently of cigarette smoking, albeit by unknown mechanisms. Our aim is to combine smoke carcinogen and genetic mouse models of lung cancer with novel mouse strains displaying emphysema to identify the processes which link the pathogenesis of emphysema to lung cancer.