Pathogen-induced Lung Injury & Repair

Prof. Elie El Agha, Ph.D.

Elie El Agha is appointed as Professor at the Institute for Lung Health (ILH), Justus-Liebig University Giessen (JLU), Germany, where he leads the research group “Pathogen-Induced Lung Injury and Repair”. He is the director of the international graduate program Molecular Biology and Medicine of the Lung (MBML) and also faculty member and co-leader of Area 3 on “Morphogenesis, Remodeling & Regeneration” at the excellence cluster Cardio-Pulmonary Institute (CPI). He is also a principal investigator and coordinator of Area C on “The Mesenchymal Cell: An Active and Powerful Modulator of the Pulmonary Scaffold into the Spatial Context” at the Diffuse Parenchymal Lung Disease (DPLD) disease area of the German Center for Lung Research (DZL).

Elie El Agha was born in Saida, Lebanon. After receiving his Bachelor degree (BSc) in Biochemistry from the Lebanese University, Beirut, Lebanon, he moved to Sweden where he did his Master degree (MSc) in molecular biology at Skövde University. For his Master thesis, he received a fellowship to work in the lab of Prof. Hans Jörnvall, Department of Medical Biochemistry and Biophysics at the Karolinska Institute, Stockholm, Sweden. In 2009, he moved to JLU, Germany, where he did his PhD and postdoctoral training on lung development and repair in the lab of Prof. Saverio Bellusci, Chair for Lung Matrix Remodeling at the Excellence Cluster Cardio-Pulmonary System (ECCPS). For his early career achievements, he was awarded two start-up grants and one intramural fund in addition to other prizes and awards. He is also a member of the editorial board of the American Journal of Physiology – Lung Cellular and Molecular Physiology, and served as guest editor at Canadian Respiratory Journal and Frontiers in Cell and Developmental Biology. He published 37 scientific articles (Date 15^th Jan 2021) in reputable scientific journals in the fields of stem cells, development, cell biology and pulmonary research such as Cell Stem Cell, Nature Communications, Developmental Cell, EMBO Journal, Cell Reports, Stem Cells, Journal of Pathology, Development, PLoS Pathogens, BMC Biology, American Journal of Physiology – Lung Cellular and Molecular Physiology, Developmental Dynamics and others.

The El Agha lab focuses on the cellular and molecular mechanisms mediating lung development and repair, particularly the interaction between mesenchymal niche cells and their epithelial partners along the proximo-distal axis in the respiratory tree. The lab is interested in the involvement of developmental signaling mechanisms in disease progression versus resolution, especially in the context of pathogen-induced lung injury.

Lung injury resulting from bacterial or viral infections represents a serious threat to global health. For instance, influenza A virus and coronavirus outbreaks can lead to pandemics resulting in millions of deaths worldwide. Pneumonia is one of the most common causes of acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). The latter is defined by the acute onset of noncardiogenic pulmonary edema, hypoxemia and the need for mechanical ventilation. Among the prominent features of ARDS are diffuse alveolar damage and collagen deposition. Pathogen-induced lung diseases are associated with a high socio-economic burden and they mostly lack preventive or curative therapy. In this context, available therapeutic options for affected patients are predominantly supportive and are incapable of efficiently inducing regeneration in damaged lungs. Importantly, pathogen-induced pneumonia per se not only leads to acute life-threatening conditions such as ARDS but also 1) acts as a secondary hit that contributes to the initiation of fatal and progressive lung diseases such as idiopathic pulmonary fibrosis (IPF) and 2) represents a comorbidity that contributes to exacerbations such as in chronic obstructive pulmonary disease (COPD) and IPF. Thus, acute exacerbations and hospitalization due to pathogen-induced lung injury represent an increased risk in patients with chronic lung disease. Therefore, better understanding of the cellular and molecular cues that mediate pathogen-induced lung injury and the associated repair mechanisms is an urgent clinical need. In this regard, there is a general consensus that developmental processes of lung morphogenesis are recapitulated or at least mimicked in lung repair during adult life.

Figure 1: Overview of the research topics addressed in the El Agha lab

In recent years, we investigated basic mechanisms of lung organogenesis, including the cellular and molecular signaling cues that govern the behavior of progenitor cells during embryonic and postnatal lung development. We focused on the involvement of growth factor signaling in mediating the crosstalk between epithelial and mesenchymal cells and contributed to delineating the lineage tree of the lung mesenchyme not only during embryonic and postnatal lung development but also during lung disease in the adult stage. We demonstrated that phenotypic plasticity of mesenchymal cells is at the heart of both disease progression and resolution, and that reconstituting the mesenchymal niche is critical for proper lung regeneration. Among the pathways of interest are FGF, hedgehog, WNT, PPARg, TGFb and PDGFRa signaling pathways. Against this background, the professorship for Pathogen-Induced Lung Injury and Repair aims to establish a “Repair Blueprint” for the lung by focusing on the following aspects:

1. Understanding the spatiotemporal dynamics of mesenchymal niche cells and epithelial stem and progenitor cells along the proximo-distal axis in the lung in response to pathogen-induced lung injury.

• Determining cellular heterogeneity and deconvoluting complex signaling networks.
• Utilizing transgenic mice to study cell-fate decision making, reveal lineage hierarchy and target specific cellular subsets.

2. Deciphering the mode of interaction between mesenchymal niche cells and epithelial stem and progenitor cells during homeostasis as well as disease progression and resolution.

• The use of in vivo models in addition to ex vivo/in vitro functional assays to test key signaling mediators that are involved in intercellular communication and evaluate their impact on disease severity versus regeneration.

3. Studying the mechanisms that reengage developmental signaling pathways in disease development and resolution.
4. Development of novel in vivo tools that allow studying and genetically manipulating stem-cell niches during lung development and repair.
5. The use of human lung-derived material (such as culturing primary cells and viable slices) and the establishment of organoids derived from human lung cells to evaluate potential therapeutic candidates identified using the mouse models.

Contact

Prof. Elie El Agha, Ph.D.
Professor for Pathogen-Induced Lung Injury and Repair at the Institute for Lung Health (ILH)
Director of the international graduate program Molecular Biology and Medicine of the Lung (MBML)
Cardio-Pulmonary Institute (CPI)
Member of the German Center for Lung Research (DZL)
Universities of Giessen and Marburg Lung Center (UGMLC)

Justus-Liebig University Giessen
Aulweg 132
35392 Giessen

Tel: +49 (0) 641 99 36481 (office)
Tel: +49 (0) 641 99 36482 (lab)
Fax: +49 (0) 641 99 36429

Email:
elie.el-agha@innere.med.uni-giessen.de

Web:
https://www.uni-giessen.de/fbz/fb11/forschung/graduierte/mbml

Ten most important publications

1. 1. Chu X, Lingampally A, Moiseenko A, Kheirollahi V, Vazquez-Armendariz AI, Koepke J, Khadim A, Kiliaris G, Shahriari Felordi M, Zabihi M, Shalashova I, Alexopoulos I, Günther S, Lebrigand K, Truchi M, Günther A, Braun T, Mari B, Samakovlis C, Li X, Seeger W, Herold S, Zhang J-S, Bellusci S, El Agha E. GLI1+ cells are a source of repair-supportive mesenchymal cells (RSMCs) during airway epithelial regeneration. Cell Mol Life Sci. 79(11):581, 2022. IF: 9.2
   2. Moiseenko A, Vazquez-Armendariz AI, Kheirollahi V, Chu X, Tata A, Rivetti S, Günther S, Lebrigand K, Herold S, Braun T, Mari B, De Langhe S, Kwapiszewska G, Günther A, Chen C, Seeger W, Tata PR, Zhang J-S, Bellusci S, El Agha E. Identification of a repair-supportive mesenchymal cell (RSMC) population during airway epithelial regeneration. Cell Rep.33(12):108549, 2020. IF: 9.9
   3. Kheirollahi V, Wasnick RM, Biasin V, Vazquez-Armendariz AI, Chu X, Moiseenko A, Weiss A, Wilhelm J, Zhang J-S, Kwapiszewska G, Herold S, Schermuly RT, Mari B, Li X, Seeger W, Günther A, Bellusci S, El Agha E. Metformin induces lipogenic differentiation in myofibroblasts to reverse lung fibrosis. Nat Commun.10(1):2987, 2019. IF: 17.6
   4. El Agha E, Schwind F, Ruppert C, Günther A, Bellusci S, Schermuly RT, Kosanovic D. Is the fibroblast growth factor signaling pathway a victim of receptor tyrosine kinase inhibition in pulmonary parenchymal and vascular remodeling? Am J Physiol Lung Cell Mol Physiol., 315(2): L248-L252, 2018. IF: 6.0
   5. El Agha E, Moiseenko A, Kheirollahi V, De Langhe S, Crnkovic S, Kwapiszewska G, Szibor M, Kosanovic D, Schwind F, Schermuly RT, Henneke I, MacKenzie B, Quantius J, Herold S, Ntokou A, Ahlbrecht K, Braun T, Morty RE, Günther A, Seeger W, Bellusci S. Two-way conversion between lipogenic and myogenic fibroblastic phenotypes marks the progression and resolution of lung fibrosis. Cell Stem Cell, 20(2):261-273.e3, 2017. IF: 25.2
   6. El Agha E, Kramann R, Schneider RK, Li X, Seeger W, Humphreys BD, Bellusci S. Mesenchymal stem cells in fibrotic disease. Cell Stem Cell, 21(2):166-177, 2017. IF: 25.2
   7. Moiseenko A, Kheirollahi V, Chao CM, Ahmadvand N, Quantius J, Wilhelm J, Herold S, Ahlbrecht K, Morty RE, Rizvanov AA, Minoo P, El Agha E*, Bellusci S*. Origin and characterization of alpha smooth muscle actin-positive cells during murine lung development. Stem Cells, 35(6):1566-1578, 2017. IF: 5.8
   8. El Agha E, Kheirollahi V, Moiseenko A, Seeger W, Bellusci S. Ex vivo analysis of the contribution of FGF10+cells to airway smooth muscle cell formation during early lung development. Dev Dyn. 246(7):531-538, 2017. IF: 2.8
   9. Al Alam D*, El Agha E*, Sakurai R, Kheirollahi V, Moiseenko A, Danopoulos S, Shrestha A, Schmoldt C, Quantius J, Herold S, Chao CM, Tiozzo C, De Langhe S, Plikus M, Thornton M, Grubbs B, Minoo P, Rehan VK, Bellusci S. Evidence for the involvement of fibroblast growth factor 10 in lipofibroblast formation during embryonic lung development. Development, 142(23):4139-50, 2015. IF: 6.8
   10. El Agha E, Herold S, Al Alam D, Quantius J, MacKenzie B, Carraro G, Moiseenko A, Chao CM, Minoo P, Seeger W, Bellusci S. Fgf10-positive cells represent a progenitor cell population during lung development and postnatally. Development, 141(2):296-306, 2014. IF: 6.8

Here you can find all ILH-publications

Funding

Group Members

Doctoral Students

Georgios Kiliaris, Ali Khadim, Mahsa Zabihi, Mahtab Shahriari Felordi

Technical Assistant

Hannah Hofmann

Project Coordinator

Dr. Sezin Czarnecki

Alumni

Alena Moiseenko, Vahid Kheirollahi, Felix Schwind, Xuran Chu, Laith Salama