COPD-iNET

About the network

Our vision is to expand the understanding of COPD pathomechanisms and translate our knowledge into novel therapies to reduce the burden of COPD on patients and society.

The network´s primary focus is the advancement of translational COPD research by discussing ongoing projects, cutting edge human in vitro models, state-of-the art systems biology approaches and clinical cohorts. We strive to identify and enable synergies to facilitate the discovery of novel COPD pathomechanisms. By fostering new collaborations and ideas to transform our understanding of COPD, we aim to ignite novel research directions and therapeutic avenues thereby paving the way to eliminate COPD.

To this end, we bring together world-wide experts on basic, preclinical and clinical COPD research in monthly online meetings and in-person meetings at major respiratory conferences. Once per year we bring together all members in a COPD-iNET symposium (2023 in Munich). Developing a database for sharing resources, expertise, education, and mentoring is a priority, in conjunction with collaborative consortia to be competitive in high level funding opportunities.

If you want to join the network, please reach out to us.

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COPD -iNET

About our Research

COPD

COPD is a progressive pulmonary disorder, especially amongst the elderly, presenting with largely irreversible airflow limitation, a result of chronic bronchitis and/or irreversible damage of the lung tissue (emphysema). COPD is the 3^rd leading cause of death worldwide(Collaborators, 2020). It affects more than 400-600 million people globally, killing over 3 million people per year, with no curative therapy currently available(Vogelmeier et al., 2017). The staggering socio-economic burden that comes with COPD treatment is now surpassing any other disease(May and Li, 2015). Among 23 EU member states, average prevalence is 15-20%, which increases with age (source: European Lung Foundation). COPD is a heterogeneous disease encompassing multiple organs beyond the lungs. Both pulmonary and extrapulmonary pathology cause a high clinical and societal burden. COPD has long been considered a disease of smoking, but only a fraction of exposed individuals develop disease, which is currently incompletely understood(Stolz et al., 2022). Ample evidence suggests vulnerability for COPD development stems from (epi)genetic risk factors and interaction with environmental exposure across the life course, as early as in childhood(Lange et al., 2015), aging of the global population, and poor dietary quality intake combined with sedentary behaviour. A major hurdle remains the identification of different disease endotypes, early detection and cellular and molecular mechanisms of early disease development. Despite the heterogeneity of the disease, diagnostic approaches have not markedly changed in decades and patients are not stratified according to condition, explaining therapy and clinical trial failure(Stolz et al., 2022). To change this, we need a better understanding of pathophysiological mechanisms. ... read more

Here, a major chance lies in the international collaboration of basic, translational and clinical researchers, which is so far not well organized. To change this, we have established COPD-iNET. The network´s primary focus is the advancement of translational COPD research by discussing ongoing projects, cutting edge human in vitro models, state-of-the art systems biology approaches and clinical cohorts. We strive to identify and enable synergies to facilitate the discovery of novel COPD pathomechanisms. By fostering new collaborations and ideas to transform our understanding of COPD, we aim to ignite novel research directions and therapeutic avenues thereby paving the way to eliminate COPD.

The network aims at a) exchanging scientific knowledge, b) sharing models and resources c) connecting the right people to facilitate joined research projects and grant proposals. The network identified key areas for future COPD research: 1. COPD cohorts, 2. Systems biology, 3. Immunity, and 4. Repair and regeneration.

Collaborators, G.B.D.C.R.D. (2020). Prevalence and attributable health burden of chronic respiratory diseases, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017. The Lancet. Respiratory medicine 8, 585-596. 10.1016/S2213-2600(20)30105-3.

Lange, P., Celli, B., Agusti, A., Boje Jensen, G., Divo, M., Faner, R., Guerra, S., Marott, J.L., Martinez, F.D., Martinez-Camblor, P., et al. (2015). Lung-Function Trajectories Leading to Chronic Obstructive Pulmonary Disease. The New England journal of medicine 373, 111-122. 10.1056/NEJMoa1411532.

May, S.M., and Li, J.T. (2015). Burden of chronic obstructive pulmonary disease: healthcare costs and beyond. Allergy and asthma proceedings 36, 4-10. 10.2500/aap.2015.36.3812.

Stolz, D., Mkorombindo, T., Schumann, D.M., Agusti, A., Ash, S.Y., Bafadhel, M., Bai, C., Chalmers, J.D., Criner, G.J., Dharmage, S.C., et al. (2022). Towards the elimination of chronic obstructive pulmonary disease: a Lancet Commission. Lancet 400, 921-972. 10.1016/S0140-6736(22)01273-9.

Vogelmeier, C.F., Criner, G.J., Martinez, F.J., Anzueto, A., Barnes, P.J., Bourbeau, J., Celli, B.R., Chen, R., Decramer, M., Fabbri, L.M., et al. (2017). Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Lung Disease 2017 Report. GOLD Executive Summary. American journal of respiratory and critical care medicine 195, 557-582. 10.1164/rccm.201701-0218PP.

Immunity

Led by Thomas Conlon / Francesca Polverino

Inflammation has long been considered as the main hallmark of COPD pathogenesis. However, with the tools and techniques available today, we can now leverage our understanding of the lung immune microenvironment to dissect out immune cell interactions and consequences to lung injury and repair, and to ultimately identify novel immune therapeutic targets. Our network aims at bringing together COPD immunologists, to foster further collaborative efforts to embrace this vision. ... read more

We have recently identified the importance of epigenetic regulation of myeloid cells in driving COPD pathogenesis (Gunes Gunsel et al., 2022) and furthered our understanding of the contribution of adaptive immune cells to COPD pathogenesis by highlighting the role of B and T cells and lymphotoxin signalling in the onset and progression of emphysema (Conlon et al., 2020). We are implementing the combined use of omics techniques, such as single cell RNAsequencing, spatial transcriptomics, (Polverino et al., 2022; Yang et al., 2022), and radiomics (Sullivan et al., 2019), to understand how the integration of omics can lead to a better characterization of COPD phenotypes and endotypes. By working together, we hope we can pave the way to disease-modifying therapies that target only deleterious immune cell subsets or their harmful products in a selected subset of COPD with off-targeted immune responses.

Conlon, T.M., John-Schuster, G., Heide, D., Pfister, D., Lehmann, M., Hu, Y., Ertuz, Z., Lopez, M.A., Ansari, M., Strunz, M., et al. (2020). Inhibition of LTbetaR signalling activates WNT-induced regeneration in lung. Nature 588, 151-156. 10.1038/s41586-020-2882-8.
Gunes Gunsel, G., Conlon, T.M., Jeridi, A., Kim, R., Ertuz, Z., Lang, N.J., Ansari, M., Novikova, M., Jiang, D., Strunz, M., et al. (2022). The arginine methyltransferase PRMT7 promotes extravasation of monocytes resulting in tissue injury in COPD. Nature communications 13, 1303. 10.1038/s41467-022-28809-4.
Polverino, F., Mirra, D., Yang, C.X., Esposito, R., Spaziano, G., Rojas-Quintero, J., Sgambato, M., Piegari, E., Cozzolino, A., Cione, E., et al. (2022). Similar programmed death ligand 1 (PD-L1) expression profile in patients with mild COPD and lung cancer. Sci Rep 12, 22402. 10.1038/s41598-022-26650-9.
Sullivan, J.L., Bagevalu, B., Glass, C., Sholl, L., Kraft, M., Martinez, F.D., Bastarrika, G., de-Torres, J.P., San Jose Estepar, R., Guerra, S., and Polverino, F. (2019). B Cell Adaptive Immune Profile in Emphysema-Predominant COPD. Am J Respir Crit Care Med 200, 1434-1439. 10.1164/rccm.201903-0632LE.
Yang, C.X., Tomchaney, M., Landecho, M.F., Zamacona, B.R., Marin Oto, M., Zulueta, J., Malo, J., Knoper, S., Contoli, M., Papi, A., et al. (2022). Lung Spatial Profiling Reveals a T Cell Signature in COPD Patients with Fatal SARS-CoV-2 Infection. Cells 11. 10.3390/cells11121864.

Clinical Cohorts

Led by Ian Adcock / Enid Neptune

We recognize the importance of clinical cohorts in facilitating reverse translational approaches (Key Area 1) [1]. Due to the multifactorial nature of COPD, research requires large and well-defined clinical cohorts to understand the pathogenesis of the disease. By combining well-defined clinical cohorts, researchers can identify disease endotypes and design effective clinical trials. In the era of “omics,” where genomics, transcriptomics, and proteomics are considered essential for precision medicine, linking existing COPD ... read more

System Medicine

Led by Theodore S. Kapellos / Maor Sauler

The advent of omics technologies and the development of powerful computational approaches have revolutionized the field of respiratory medicine and now allow the study of patient heterogeneity, as well as the molecular pathways that drive chronic lung diseases at single-cell resolution. One of COPD-iNET research pillars focuses on the application of systems medicine methodologies and bioinformatics analysis to clinical samples and animal models of COPD with the aim to characterize the ... read more

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Regeneration

Led by Mareike Lehmann / Reinoud Gosens:

The goal of the COPD network is to contribute to regenerating COPD lungs, which is why key area 4 is focused on understanding the impaired repair and regeneration capacity in COPD lungs (Melo-Narvaez et al., 2020; Wu et al., 2022). Cigarette smoke exposure, air pollution, respiratory infections and aging contribute to cellular senescence and to impaired lung regeneration in COPD. Imbalanced immunity likely impacts regenerative capacity (Conlon et al., 2020), ... read more

Participating Groups

Yildirim / Conlon Lab, LHI

Immunopathology of COPD

We want to understand how the immune system drives tissue injury and modulates tissue repair and regeneration in COPD to devise novel therapeutic targets to ultimately reverse chronic lung disease – particularly COPD.

COPD-iNET

About the network

COPD -iNET

On this page

About our Research

COPD

Immunity

Clinical Cohorts

System Medicine

Regeneration

Participating Groups

Yildirim / Conlon Lab, LHI

Immunopathology of COPD

Kapellos Lab, LHI

Immunoregulation in obstructive airway diseases

Lehmann Lab, LHI, Professor of translational inflammation research, Philips University Marburg

Lung Inflammaging

Irfan Rahman Lab, URMC

Oxidant and cigarette smoke-mediated lung inflammation

Benam Lab, UPMC

Translational and Multidisciplinary Lung Microengineering Lab

Tien Peng Lab, UCSF

The Fibroblast´s Guide to the Galaxy

Singanayagam Lab, ICL

Investigating the role of respiratory tract mucins in mucosal host-defence

PulmoScience Lab, LUMC

Lung repair and regeneration

Donelly / Barnes Lab, ICL

The role of inflammageing and immunosenescence

Cloonan Lab, TCD

Metabolism in Lung Biology and Disease

Schmeck Lab, iLung

Extracellular Vesicles and Infection in lung diseases

Polverino Lab, BCMH

understanding the immune mechanisms underlying COPD

Outtz Reed Lab, WCM

Thrombin activation and lung lymphatic thrombosis in the pathogenesis of COPD

Philip Hansbro Lab, UTS

Centenary UTS Centre for Inflammation

Reinoud Gosens Lab, UoG

Professor Translational Pharmacology

Silke Meiners Lab, CAU Kiel

Chair Immunoproteasome Research, CAU Kiel

Irfan Rahman Lab, URMC

Oxidant and cigarette smoke-mediated lung inflammation

Events / Seminare

Person Meeting at ATS 2023 Washington DC, Tuesday May 23, 4pm-6pm

Organizers

Dr. Ali Önder Yildirim

Director of Lung Health and Immunity, Helmholtz Centrum, Munich, Germany

Dr. Thomas Conlon

Head of research group “Immunopathology of COPD”

Prof. Dr. Mareike Lehmann

Head of research group “Lung inflammaging”

Dr. Theodoros Kapellos

Head of research group “Immunoregulations in obstructive respiratory diseases”

Prof. Dr. Reinoud Gosens

Professor Translational Pharmacology, University of Groningen

Francesca Polverino, MD, PhD

Lester and Sue Smith Associate Professor, Baylor College of Medicine – Housten

Maor Sauler, MD

Associate Professor of Medicine, Yale School of Medicine

Enid R. Neptune, MD

Associate Professor of Medicine, John Hopkins Medicine

Professor Ian Adcock,

Faculty of Medicine, National Heart & Lung Institute, Imperial College London,