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New approaches to uncover COPD pathobiology and develop therapies
Yohannes Tesfaigzi, Ali Önder Yildirim, Francesca Polverino, Thomas M. Conlon, Venkataramana Sidhaye, Maor Sauler, S. Vamsee Raju, Renata Z. Jurkowska, Divay Chandra, Michael H. Cho, Edwin K. Silverman, Ramon C. Sun, Peter Castaldi, Purushothama Rao Tata, Kambez H. Benam, Linto Antony, Mareike Lehmann, Beata Kosmider, Karim Bahmed, Zerihun H. Negasi, Kamakshi Bankoti, Carter Swaby, Dave A. Lagowala, Yeşim Vural, Hasan Bayram, Rosa Faner, George Washko, Dinh Son Bui, Bartolome Celli, Roxana Maria Wasnick, Enid Neptune
Yohannes Tesfaigzi, Ali Önder Yildirim, Francesca Polverino, Thomas M. Conlon, Venkataramana Sidhaye, Maor Sauler, S. Vamsee Raju, Renata Z. Jurkowska, Divay Chandra, Michael H. Cho, Edwin K. Silverman, Ramon C. Sun, Peter Castaldi, Purushothama Rao Tata, Kambez H. Benam, Linto Antony, Mareike Lehmann, Beata Kosmider, Karim Bahmed, Zerihun H. Negasi, Kamakshi Bankoti, Carter Swaby, Dave A. Lagowala, Yeşim Vural, Hasan Bayram, Rosa Faner, George Washko, Dinh Son Bui, Bartolome Celli, Roxana Maria Wasnick, Enid Neptune
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Review

New approaches to uncover COPD pathobiology and develop therapies

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Abstract

Chronic obstructive pulmonary disease (COPD) was the third leading cause of global mortality in 2011 but receives limited attention and research funding. This Review describes the current knowledge on COPD risk factors, including genetic and epigenetic determinants and their interactions with the microbiome and environmental exposures. Preclinical models are being refined and single-cell transcriptomic, metabolomic, and proteomic technologies are being implemented to investigate the molecular mechanisms of disease progression. Patient cohorts to define biomarkers of early disease and the latest approaches to diagnose pre-COPD are essential to accelerate the development of novel and effective therapeutic interventions and translate new findings into clinical trials. This Review is a summary of topics covered by a symposium organized by the COPD-iNET consortium, an international network of researchers who have established a platform that facilitates collaboration of this multidisciplinary group of preclinical, translational, and clinical researchers.

Authors

Yohannes Tesfaigzi, Ali Önder Yildirim, Francesca Polverino, Thomas M. Conlon, Venkataramana Sidhaye, Maor Sauler, S. Vamsee Raju, Renata Z. Jurkowska, Divay Chandra, Michael H. Cho, Edwin K. Silverman, Ramon C. Sun, Peter Castaldi, Purushothama Rao Tata, Kambez H. Benam, Linto Antony, Mareike Lehmann, Beata Kosmider, Karim Bahmed, Zerihun H. Negasi, Kamakshi Bankoti, Carter Swaby, Dave A. Lagowala, Yeşim Vural, Hasan Bayram, Rosa Faner, George Washko, Dinh Son Bui, Bartolome Celli, Roxana Maria Wasnick, Enid Neptune

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Figure 2

Evolving landscape of COPD research.

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Evolving landscape of COPD research.
GWAS provide information on suscept...
GWAS provide information on susceptibility genes and DNA methylation. ChIP-seq and ATAC-seq from appropriate tissues provide epigenetic modifications that are associated with environmental factors. Data from specific tissues and cell types generate QTL information that points to genes and reliable information on pathways involved in affecting cellular phenotypes and pathways that could be initiators of disease. This in turn can be used to develop appropriate preclinical COPD models that capture the gene-and-environment interaction. Applying deep learning algorithms to scRNA-seq and spatial RNA-seq data from preclinical and pre-COPD cohort samples, together with the GWAS and QTL data, can be used to understand COPD heterogeneity. An iterative process of data analysis and retesting in experimental models and findings from pre-COPD cohorts helps to prioritize for testing appropriate drugs that will be successful in clinical trials and have minimal side effects.

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ISSN 2379-3708

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