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.
Molecular Characterisation Of TRAIL-regulated Signal Transduction Pathways And Their Role In The Development, Persistence, And Exacerbation Of Allergic Airways Disease
Funder
National Health and Medical Research Council
Funding Amount
$637,035.00
Summary
Molecules that promote the development, persistence, and exacerbation of asthma are only poorly defined. We have discovered a novel signalling pathway that is activated in the airway wall during asthma. Blocking a molecule that activates this pathway ameliorated asthma in mice. We now want to identify all the important components of this pathway and therapeutically modulate them to prevent the development, persistence, and exacerbation of asthma.
Role Of Amnion Derived Stem Cells In Reducing Lung Fibrosis
Funder
National Health and Medical Research Council
Funding Amount
$349,485.00
Summary
Human amniotic epithelial multipotential cells from the term placenta are being studied in a mouse model of pulmonary fibrosis-emphysema to demonstrate their anti-inflammatory, anti-fibrotic, immune-suppresive and lung repair capability. The availability and numbers of these cells from discarded placentas at birth are unlimited and their potential to repair serious lung disease would have strong clinical interest as a new stem cell therapy.
The Role Of Src Family Tyrosine Kinases In Inflammatory Lung Disease And Cancer
Funder
National Health and Medical Research Council
Funding Amount
$535,333.00
Summary
We aim to learn why some people develop COPD, a serious lung disease, and adenocarcinoma, a common fatal lung cancer. COPD is mostly caused by cigarette smoke which induces lung inflammation. Lung inflammation, which involves macrophage activation, is a major cancer risk. Macrophages can destroy lung tissue, and they may promote cancer development. We will study the role of Src kinases, which can regulate macrophage activation, which may lead to new treatments for these diseases.
Regulation Of Pulmonary Immune Responses To Subunit Vaccines Against Tuberculosis
Funder
National Health and Medical Research Council
Funding Amount
$509,202.00
Summary
Tuberculosis (TB) remains an enormous health problem world-wide. Improving the effectiveness of anti-TB vaccines is essential for its control. The first approach to improving subunit TB vaccines will be to manipulate the cellular immune response to the vaccine by increasing the positive cytokine signals, or reducing inhibitory effects on the immune response. The second approach is to develop new subunit vaccines to deliver to the lung in order to increase the potency of the protective response.
THE ROLE OFPROTEASES AND PROTEASE ACTIVATED RECEPTORS IN RESPIRATORY EPITHELIAL CELL FUNCTION IN ASTHMA
Funder
National Health and Medical Research Council
Funding Amount
$457,500.00
Summary
The epithelium lines the airways and is, therefore, constantly exposed to a variety of exogenous antigens, infectious agents and noxious stimuli. This tissue responds to such stimuli by secreting substances that help counteract the insult while simultaneously initiating healing and repair. In this proposal, we will investigate the role of a group of receptors present on the surface of the epithelium which monitor the area surrounding the epithelium for the presence of enzymes which digest host t ....The epithelium lines the airways and is, therefore, constantly exposed to a variety of exogenous antigens, infectious agents and noxious stimuli. This tissue responds to such stimuli by secreting substances that help counteract the insult while simultaneously initiating healing and repair. In this proposal, we will investigate the role of a group of receptors present on the surface of the epithelium which monitor the area surrounding the epithelium for the presence of enzymes which digest host tissue or pathogens. These receptors, known as PAR, sense their suroundings by binding the protease, a process which then triggers the cell to respond in an appropriate way by releasing cytokines and mediators. There are 4 PAR, each with different properties, and are present on many cells of the body. However, little information about their role on epithelium exists. Although we have shown them to be upregulated in the epithelium in the socio-economically important disease, asthma, their function in this disease remains elusive. We will, therefore, initiate studies to define their role in inflammation, healing and repair as this information may lead to a better understanding of their role in disease which may then translate into better treatment.Read moreRead less
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