Post on 17-Aug-2020
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Lung Research – future directions for LIWA
Yuben Moodley
INTRODUCTION
• If you think about the following diseases: • COPD, emphysema, asthma, cystic
fibrosis, lung cancer, bronchiectasis, asbestosis, lung fibrosis, sarcoidosis
• You will appreciate that 1 in 4 Australians have lung disease
INTRODUCTION
• COPD-emphysema and bronchitis by 2020 will be the 3rd commonest cause of global morbidity and mortality.
• If you add certain infections such as TB then lung disease is a major global crisis
INTRODUCTION
The surface area of the lung is 70m2
10 000l/day of air
Oxygen consumption 250 to 5500 ml/min
Pulmonary blood flow 4 to 40l/min
LUNG DISEASE THE SILENT SUFFERERS
• Short of breath - you withdraw
• These people need advocates
The Lung Institute of WA (LIWA) Our aims
– Support high quality research into the treatment and management of lung diseases.
– Support research into associated conditions.
– Improve the well-being of patients.
– Support the careers of young scientists.
– Provide a strong educational and scientific resource for the community.
– Be an advocacy group for better lung health.
THE ALGORITHM OF DISEASE Genetics, epigenetics Injury
Inflammation
Normal repair and regeneration
Impaired/pathological repair
Fibrosis cancer
Chronic lung disease
THE ALGORITHM OF DISEASE Genetics, epigenetics Injury/Infection
Inflammation
Normal repair and regeneration
Impaired/pathological repair
Fibrosis cancer
Chronic lung disease
GENETICS Prof Philip Thompson Dr Svetlana Baltic
PLEURAL Prof Gary Lee
TISSUE REPAIR GROUP Prof Steven Mustsaers A/Prof Cecilia Prele STEM CELL
A/Prof Yuben Moodley
CLINICAL TRIALS UNIT Prof Philip Thompson CYSTIC FIBROSIS Dr Siobhan Mulroonan PHYSIOTHERAPY A/Prof Sue Jenkins ADVANCED LUNG Prof Eli Gabbay
Asthma, COPD
FUNDING STRATEGY
• Cutting edge research
• Collaboration
• Community engagement
COLLABORATION
WESTERN AUSTRALIA AUSTRALIA INTERNATIONAL
THE THREE PICTURE RATING
Molecular Genetics and Inflammation Unit
Genetics, epigenetics Injury/Infection
Inflammation
Normal repair and regeneration
Impaired/pathological repair
Fibrosis cancer
Chronic lung disease
GENETICS Prof Philip Thompson Dr Svetlana Baltic
Asthma, COPD
Molecular Genetics and Inflammation Unit
Why? Current treatments are not effective for everyone How? • use of LIWA cohort of over 1200 asthmatics with the largest cohort of severe asthmatics
•Genotyping of ADRβ2 polymorphisms
•Investigating pharmacogenetic effect of ADRβ2 polymorphisms on receptor expression and activation in the presence or absence of ADRβ2 agonists (eg. Ventolin)
PERSONALIZED TREATMENT FOR ASTHMA
Molecular Genetics and Inflammation Unit
Developing New Treatments for Lung Diseases
ASTHMA COPD
BRONCHIECTASIS CYSTIC FIBROSIS
• Identifying new molecular targets
• Generating more effective treatments
• Halting disease progression
• Inhibition of the cycle of chronic inflammation
Big cohort of patients with inflammatory airway diseases
Molecular Genetics and Inflammation Unit
1) Genotyping and association studies, – Australian Genetic Consortium, National International
Collaborations Publications (Nature Genetics, Lancet, etc) Pharmaceutical Companies
2) Explore different strategies of modifying gene expression – CRC for Asthma and Airways, National Multicentre Collaboration – Patient, publications
3) Research in the field of pharmacogenetics, – University of Adelaide, Brisbane
4) Discover molecular mechanisms of gene regulation, splicing and expression – Local and National, potential for International Collaborations
TISSUE REPAIR GROUP Genetics, epigenetics Injury/Infection
Inflammation
Normal repair and regeneration
Impaired/pathological repair
Fibrosis cancer
Chronic lung disease
TISSUE REPAIR GROUP Prof Steven Mustsaers A/Prof Cecilia Prele
Asthma, COPD
TISSUE REPAIR GROUP IDIOPATHIC PULMONARY FIBROSIS (IPF)
TISSUE REPAIR GROUP
GP130
STAT 3 MAPK
INCREASED LUNG FIBROSIS
PROTECTIVE AGAINST LUNG FIBROSIS
STAT3 regulation of cell responses in IPF
TISSUE REPAIR GROUP
LUNG FIBROSIS IL-6/gp130/STAT signalling in the pathogenesis of pulmonary fibrosis. The role of the epithelium in regulating B cell activity (G Laurent, G Hoyne, M Ernst, R O’Donoghue)
SOCS-mediated regulation of STAT signalling in IPF BARD-1 in the pathogenesis of lung fibrosis (G Laurent and I Irminger-Finger) Role of Fibulin-1 in IPF (J Burgess and J Black)
MESOTHELIOMA Collagen/TGF-β signalling in mesothelioma (G Laurent, R McAnulty) MiRNAs in mesothelioma: diagnostic and biological role (W Musk G Reid, M Kirschner, J Creaney, B Robinson, G Lee) Hedgehog signalling pathway in mesothelial repair and the pathogenesis of mesothelioma: mutations, mechanisms, therapeutics (N Watkins, A Nowak) BARD-1 in the pathogenesis of mesothelioma (I Irminger-Finger)
Plasticity of mesothelial cells (R Dilley)
PLEURAL GROUP Genetics, epigenetics Injury/Infection
Inflammation
Normal repair and regeneration
Impaired/pathological repair
Fibrosis cancer
Chronic lung disease
PLEURAL Prof Gary Lee
Asthma, COPD
PLEURAL GROUP
CLINICAL PLEURAL SERVICE
PATIENT BASED RESEARCH
LABORATORY RESEARCH
PLEURAL GROUP
PLEURAL GROUP
New Molecular Targets
Novel Concepts for Fluid Control
MALIGNANT PLEURAL EFFUSION
MPM Gene Profiling
IPC complication studies
Phase III: IPC vs Talc
Novel Biomarkers
WA MPE study
PLEURAL GROUP
Murine model Open label Follow-up
MIST-2
Animal Model Clinical Trials
PLEURAL INFECTION
In vitro
Bacteria on mesothelial cells
PLEURAL GROUP
WA NETWORK ASIA-PACIFIC NETWORK
STEM CELL Genetics, epigenetics Injury/Infection
Inflammation
Normal repair and regeneration
Impaired/pathological repair
Fibrosis cancer
Chronic lung disease
STEM CELL A/Prof Yuben Moodley
Asthma, COPD
STEM CELL
STEM CELL GROUP-CYSTIC FIBROSIS
CFTR gene mutations
CFTR dysfunction
Altered ion transport Loss of ASL, thick viscous secretions and impaired mucociliary clearance
Chronic bacterial infection
Chronic inflammation and fibrosis
Bronchiectasis, pulmonary hypertension and cor pulmonale
STEM CELL GROUP
Figure 1. Pathogenesis of CF. In the normal airway (A), Sodium is absorbed by the cell and Chloride (Cl) is secreted by the CFTR. In CF the CFTR is defective which results in no secretion of Cl into the airway. This results in increased absorption of Na, paracellular absorption of Cl and water resulting in a reduction of the air surface liquid (ASL).
normal Cystic fibrosis
STEM CELL GROUP
WA NETWORK Cell and tissue therapy centre of WA (Dr Marian Sturm) Human studies in COPD CCTRM-Geoff Laurent CYSTIC FIBROSIS-Steve Stick and Anthony Kicic
LARGE ANIMAL MODELS VENTILATED PIG AND STEM CELLS-Manitoba (Dr Ruth Mcgrath) REPROGRAMING-pluripotent cells to lung epithelium-Barcelona-Dr Michael Edel- CYSTIC FIBROSIS-North Carolina-Dr Robert Tarran
CLINICAL TRIALS/CLINICAL SCIENCES GROUP
Genetics, epigenetics Injury/Infection
Inflammation
Normal repair and regeneration
Impaired/pathological repair
Fibrosis cancer
Chronic lung disease
CLINICAL TRIALS UNIT Prof Philip Thompson CYSTIC FIBROSIS Dr Siobhan Mulroonan PHYSIOTHERAPY A/Prof Sue Jenkins ADVANCED LUNG Prof Eli Gabbay
Asthma, COPD
• Clinical trials allow recruitment of patients for research
• Education of patients • Brings cutting edge technology and the
latest therapies to patients • Income • Trials in asthma and COPD
CLINICAL TRIALS/CLINICAL SCIENCES GROUP
LIWA-COMMUNITY ENGAGEMENT
Medical Research Seminar Series
Delirium 24-Hour Cycle Race
The Search for Perth’s Best Set of Lungs
HBF Run for a Reason
Flu Vaccination Clinic
Cook for a Cure
Chevron City to Surf
Corporate lung testing
Melbourne Cup Luncheon
World COPD Day lung testing Members’ functions
Cook for a Cure
Delirium 24-hour cycle race
Melbourne Cup Luncheon
The Search for Perth’s Best Set of Lungs
LIWA-COMMUNITY ENGAGEMENT
LIWA Grants – The Alan King Westcare Grant – The LIWA Glenn Brown
Memorial Grant – The LIWA Sarcoidosis and
Other Granulomatous Lung Diseases Project Grant
Scholarships
– PhD – Honours – Summer Vacation Cadetships
Awards
– Junior and Senior travel awards
Funds raised for the LIWA Glenn Brown Memorial Grant
OPPORTUNITES FOR COLLABORATION
• Personalized medicine • Biomarkers for diagnosis and preventative
medicine • Reversing tissue remodeling (scar) • Replace scar tissue with healthy tissue • Curing cancer
OPPORTUNITES FOR COLLABORATION
• Large animal models • Human organs for experimentation-long
term preservation • Signal transduction • Genetic and epigenetic regulation of
disease • Gene and cell delivery to the human lung • Novel imaging of disease processes