Lung Research future directions for LIWA. Yuben Moodley

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1 Lung Research future directions for LIWA Yuben Moodley

2 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

3 INTRODUCTION COPD-emphysema and bronchitis by 2020 will be the 3 rd commonest cause of global morbidity and mortality. If you add certain infections such as TB then lung disease is a major global crisis

4 INTRODUCTION The surface area of the lung is 70m l/day of air Oxygen consumption 250 to 5500 ml/min Pulmonary blood flow 4 to 40l/min

5 LUNG DISEASE THE SILENT SUFFERERS Short of breath - you withdraw These people need advocates

6 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.

7 THE ALGORITHM OF DISEASE Genetics, epigenetics Injury Inflammation Normal repair and regeneration Impaired/pathological repair Fibrosis cancer Chronic lung disease

8 THE ALGORITHM OF DISEASE GENETICS Prof Philip Thompson Dr Svetlana Baltic Genetics, epigenetics Injury/Infection PLEURAL Prof Gary Lee Asthma, COPD Inflammation CLINICAL TRIALS UNIT Prof Philip Thompson CYSTIC FIBROSIS Dr Siobhan Mulroonan Normal repair and regeneration Impaired/pathological repair PHYSIOTHERAPY A/Prof Sue Jenkins ADVANCED LUNG Prof Eli Gabbay STEM CELL A/Prof Yuben Moodley Fibrosis Chronic lung disease cancer TISSUE REPAIR GROUP Prof Steven Mustsaers A/Prof Cecilia Prele

9 FUNDING STRATEGY Cutting edge research Collaboration Community engagement

10 COLLABORATION THE THREE PICTURE RATING WESTERN AUSTRALIA AUSTRALIA INTERNATIONAL

11 Molecular Genetics and Inflammation Unit GENETICS Prof Philip Thompson Dr Svetlana Baltic Asthma, COPD Genetics, epigenetics Inflammation Injury/Infection Normal repair and regeneration Impaired/pathological repair Fibrosis cancer Chronic lung disease

12 Molecular Genetics and Inflammation Unit PERSONALIZED TREATMENT FOR ASTHMA 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)

13 Molecular Genetics and Inflammation Unit Developing New Treatments for Lung Diseases 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 ASTHMA COPD BRONCHIECTASIS CYSTIC FIBROSIS

14 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

15 TISSUE REPAIR GROUP Genetics, epigenetics Injury/Infection Asthma, COPD Inflammation Normal repair and regeneration Impaired/pathological repair Fibrosis Chronic lung disease cancer TISSUE REPAIR GROUP Prof Steven Mustsaers A/Prof Cecilia Prele

16 TISSUE REPAIR GROUP IDIOPATHIC PULMONARY FIBROSIS (IPF)

17 TISSUE REPAIR GROUP STAT3 regulation of cell responses in IPF GP130 STAT 3 MAPK INCREASED LUNG FIBROSIS PROTECTIVE AGAINST LUNG FIBROSIS

18 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)

19 PLEURAL GROUP Genetics, epigenetics Injury/Infection PLEURAL Prof Gary Lee Asthma, COPD Inflammation Normal repair and regeneration Impaired/pathological repair Fibrosis cancer Chronic lung disease

20 PLEURAL GROUP CLINICAL PLEURAL SERVICE LABORATORY RESEARCH PATIENT BASED RESEARCH

21 PLEURAL GROUP

22 PLEURAL GROUP MALIGNANT PLEURAL EFFUSION New Molecular Targets MPM Gene Profiling Novel Biomarkers Novel Concepts for Fluid Control WA MPE study Phase III: IPC vs Talc IPC complication studies

23 PLEURAL GROUP PLEURAL INFECTION In vitro Animal Model Clinical Trials Bacteria on mesothelial cells Murine model Open label Follow-up MIST-2

24 PLEURAL GROUP WA NETWORK ASIA-PACIFIC NETWORK

25 STEM CELL Genetics, epigenetics Injury/Infection Asthma, COPD Inflammation Normal repair and regeneration Impaired/pathological repair Fibrosis cancer STEM CELL A/Prof Yuben Moodley Chronic lung disease

26 STEM CELL

27 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

28 STEM CELL GROUP normal Cystic fibrosis 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).

29 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) REPROGRAMINGpluripotent cells to lung epithelium-barcelona- Dr Michael Edel- CYSTIC FIBROSIS- North Carolina-Dr Robert Tarran

30 CLINICAL TRIALS/CLINICAL SCIENCES GROUP Genetics, epigenetics Injury/Infection Asthma, COPD Inflammation CLINICAL TRIALS UNIT Prof Philip Thompson CYSTIC FIBROSIS Dr Siobhan Mulroonan Normal repair and regeneration Impaired/pathological repair PHYSIOTHERAPY A/Prof Sue Jenkins ADVANCED LUNG Prof Eli Gabbay Fibrosis Chronic lung disease cancer

31 CLINICAL TRIALS/CLINICAL SCIENCES GROUP 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

32 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 Delirium 24-hour cycle race Flu Vaccination Clinic Cook for a Cure Cook for a Cure Chevron City to Surf Corporate lung testing Melbourne Cup Luncheon World COPD Day lung testing Members functions Melbourne Cup Luncheon The Search for Perth s Best Set of Lungs

33 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 Funds raised for the LIWA Glenn Brown Memorial Grant Awards Junior and Senior travel awards

34 OPPORTUNITES FOR COLLABORATION Personalized medicine Biomarkers for diagnosis and preventative medicine Reversing tissue remodeling (scar) Replace scar tissue with healthy tissue Curing cancer

35 Large animal models OPPORTUNITES FOR COLLABORATION 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

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