KFO309 - The clinical research unit Virus Induced Lung injury

Principal Investigators

Andreas Günther

Prof. Dr. med. Andreas Günther

Justus Liebig University Giessen
Department of Internal Medicine
Klinikstrasse 33; 35392 Giessen

Saverio Bellusci

Prof. Dr. rer. nat. Saverio Bellusci

Justus Liebig University Giessen
Excellence Cluster „Cardiopulmonary System“ 
Aulweg 130, 35392 Giessen

Elie El Agha

Elie El Agha , PhD

Justus Liebig University Giessen, Aulweg 130; 35392 Giessen


Role of epithelial endoplasmic reticulum stress and epithelial FGF signaling in the initiation and aggravation of lung fibrosis by viral infection


Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive and fatal parenchymal lung disease, which is proposed to originate from chronic injury to aged alveolar epithelial type 2 cells (AEC II) such as pro-apoptotic (maladaptive) endoplasmic reticulum (ER) stress. Viral infection is known to trigger progression of IPF and to aggravate the disease. Fibroblast Growth Factor 10 (FGF-10) has been shown to be important for the formation of the alveolar epithelial lineage development and for survival of AEC II in response to injury. In the preceding funding period, we could show that viral infection of AEC II undergoing maladaptive ER-stress (via CHOP) results in a boost of AEC II apoptosis and lung fibrosis, whereas adaptive ER-stress of AEC II did not. We identified the microRNA miR-142 to be linked with the formation of AEC II during lung development and to be regulated by FGF-10. Moreover, we found that FGF-10 prevents influenza virus (IV, PR8) amplification in AEC II and that a knockout of miR-142 makes AEC II more resistant to PR8. Additionally, we showed that the first-line antidiabetic drug metformin impacts FGF-10 signaling and accelerates lung regeneration after injury (Kheirollahi et al. Nat Commun, in press). Based on these results, we propose, in the forthcoming funding period, that the newly discovered FGF-10-FGFR2b-miR-142 signaling axis in the adult lung decreases viral infection of ER-stressed AEC II cells, and we envision that targeting this axis including metformin administration beneficially impacts virus-induced lung injury and regeneration. 


Disease trajectories in interstitial lung diseases - data from the EXCITING-ILD registry

Respir Res 2024 Mar 6;25(1):113. doi: 10.1186/s12931-024-02731-3

Task Force Dyspnoe Unit (DU)

Pneumologie 2024 Feb 21. German. doi: 10.1055/a-2238-4253

Hospitalisation patterns in interstitial lung diseases: data from the EXCITING-ILD registry

Respir Res 2024 Jan 4;25(1):5. doi: 10.1186/s12931-023-02588-y

Complex urban atmosphere alters alveolar stem cells niche properties and drives lung fibrosis

Am J Physiol Lung Cell Mol Physiol 2023 Oct 1;325(4):L447-L459. doi: 10.1152/ajplung.00061.2023

FGF10 mitigates doxorubicin-induced myocardial toxicity in mice via activation of FGFR2b/PHLDA1/AKT axis

Acta Pharmacol Sin 2023 Oct;44(10):2004-2018. doi: 10.1038/s41401-023-01101-x

Preferential FGF18/FGFR activity in pseudoglandular versus canalicular stage human lung fibroblasts

Front Cell Dev Biol 2023 Aug 28;11:1220002. doi: 10.3389/fcell.2023.1220002

Genetic and geographic influence on phenotypic variation in European sarcoidosis patients

Front Med (Lausanne) 2023 Aug 9;10:1218106. doi: 10.3389/fmed.2023.1218106

The Role of the Redox Enzyme p66Shc in Biological Aging of the Lung

Aging Dis 2023 Jul 27. doi: 10.14336/AD.2023.0715

The lung mesenchyme in development, regeneration, and fibrosis

J Clin Invest 2023 Jul 17;133(14):e170498. doi: 10.1172/JCI170498

Stem/Progenitor Cells and Related Therapy in Bronchopulmonary Dysplasia

Int J Mol Sci 2023 Jul 7;24(13):11229. doi: 10.3390/ijms241311229

Decoding the role of fatty acids and their metabolites in lung fibrosis

Pol Arch Intern Med 2023 Jun 30;133(7-8):16520. doi: 10.20452/pamw.16520

CEACAM6 as a Novel Therapeutic Target to Boost HO-1-mediated Antioxidant Defense in COPD

Am J Respir Crit Care Med 2023 Jun 15;207(12):1576-1590. doi: 10.1164/rccm.202208-1603OC

Definition, Composition, and Harmonization of Core Datasets Within the German Center for Lung Research

Stud Health Technol Inform 2023 May 18;302:696-700. doi: 10.3233/SHTI230242

Injury activated alveolar progenitors (IAAPs): the underdog of lung repair

Cell Mol Life Sci 2023 May 11;80(6):145. doi: 10.1007/s00018-023-04789-6

Nicotine promotes e-cigarette vapour-induced lung inflammation and structural alterations

Eur Respir J 2023 Apr 27:2200951. doi: 10.1183/13993003.00951-2022

Mesenchyme-derived vertebrate lonesome kinase controls lung organogenesis by altering the matrisome

Cell Mol Life Sci 2023 Mar 15;80(4):89. doi: 10.1007/s00018-023-04735-6

Notch1 Induces Defective Epithelial Surfactant Processing and Pulmonary Fibrosis

Am J Respir Crit Care Med 2023 Feb 1;207(3):283-299. doi: 10.1164/rccm.202105-1284OC

State of the Art in Idiopathic Pulmonary Fibrosis

Cells 2022 Aug 11;11(16):2487. doi: 10.3390/cells11162487

A role for metformin in the treatment of Dupuytren disease?

Biomed Pharmacother 2022 Jun;150:112930. doi: 10.1016/j.biopha.2022.112930

Hedgehog Signaling Pathway Orchestrates Human Lung Branching Morphogenesis

Int J Mol Sci 2022 May 9;23(9):5265. doi: 10.3390/ijms23095265

When inflammation meets lung development-an update on the pathogenesis of bronchopulmonary dysplasia

Mol Cell Pediatr 2022 Apr 20;9(1):7. doi: 10.1186/s40348-022-00137-z

SPARC, a Novel Regulator of Vascular Cell Function in Pulmonary Hypertension

Circulation 2022 Mar 22;145(12):916-933. doi: 10.1161/CIRCULATIONAHA.121.057001

Noncanonical HIPPO/MST Signaling via BUB3 and FOXO Drives Pulmonary Vascular Cell Growth and Survival

Circ Res 2022 Mar 4;130(5):760-778. doi: 10.1161/CIRCRESAHA.121.319100.

Oxygen Toxicity to the Immature Lung-Part II: The Unmet Clinical Need for Causal Therapy

Int J Mol Sci 2021 Oct 2;22(19):10694. doi: 10.3390/ijms221910694

PINK1-mediated Mitophagy Contributes to Pulmonary Vascular Remodeling in Pulmonary Hypertension

Am J Respir Cell Mol Biol 2021 Aug;65(2):226-228. doi: 10.1165/rcmb.2021-0082LE

Editorial: Branching Morphogenesis During Embryonic Lung Development

Front Cell Dev Biol 2021 Jul 12;9:728954. doi: 10.3389/fcell.2021.728954

Protocol for the generation of murine bronchiolospheres

STAR Protoc 2021 Jun 11;2(2):100594. doi: 10.1016/j.xpro.2021.100594

FGF10 and Lipofibroblasts in Lung Homeostasis and Disease: Insights Gained From the Adipocytes

Front Cell Dev Biol 2021 May 26;9:645400. doi: 10.3389/fcell.2021.645400

ISO 21526 Conform Metadata Editor for FAIR Unicode SKOS Thesauri

Stud Health Technol Inform 2021 May 24;278:94-100. doi: 10.3233/SHTI210056

WASP: a versatile, web-accessible single cell RNA-Seq processing platform

BMC Genomics 2021 Mar 18;22(1):195. doi: 10.1186/s12864-021-07469-6

The Multifunctional Contribution of FGF Signaling to Cardiac Development, Homeostasis, Disease and Repair

Front Cell Dev Biol 2021 May 14;9:672935. doi: 10.3389/fcell.2021.672935

Validation of a Novel Fgf10Cre–ERT2 Knock-in Mouse Line Targeting FGF10Pos Cells Postnatally

Front Cell Dev Biol 2021 May 13;9:671841. doi: 10.3389/fcell.2021.671841

The effect of long-term doxycycline treatment in a mouse model of cigarette smoke-induced emphysema and pulmonary hypertension

Am J Physiol Lung Cell Mol Physiol 2021 May 1;320(5):L903-L915. doi: 10.1152/ajplung.00048.2021

The Lung Vasculature: A Driver or Passenger in Lung Branching Morphogenesis?

Front Cell Dev Biol 2021 Jan 14;8:623868. doi: 10.3389/fcell.2020.623868

Interferon Regulatory Factor 9 Promotes Lung Cancer Progression via Regulation of Versican

Cancers (Basel) 2021 Jan 8;13(2):208. doi: 10.3390/cancers13020208

Targeting Jak-Stat Signaling in Experimental Pulmonary Hypertension

Am J Respir Cell Mol Biol 2021 Jan;64(1):100-114. doi: 10.1165/rcmb.2019-0431OC

Identification of a Repair-Supportive Mesenchymal Cell Population during Airway Epithelial Regeneration

Cell Rep 2020 Dec 22;33(12):108549. doi: 10.1016/j.celrep.2020.108549

A FOX-like Mechanism Regulating Lung Fibroblasts: Are We Getting There?

Am J Respir Cell Mol Biol 2020 Dec;63(6):723-724. doi: 10.1165/rcmb.2020-0441ED

p16 INK4a and the Alveolar Niche Take Center Stage in Bronchopulmonary Dysplasia

Am J Respir Crit Care Med 2020 Oct 15;202(8):1065-1067. doi: 10.1164/rccm.202006-2164ED

Corrigendum: An FGFR/AKT/SOX2 Signaling Axis Controls Pancreatic Cancer Stemness

Front Cell Dev Biol 2020 Oct 2;8:594589. doi: 10.3389/fcell.2020.594589

Fgf10/Fgfr2b Signaling in Mammary Gland Development, Homeostasis, and Cancer

Front Cell Dev Biol 2020 Jun 26;8:415. doi: 10.3389/fcell.2020.00415

NADPH oxidase subunit NOXO1 is a target for emphysema treatment in COPD

Nat Metab 2020 Jun;2(6):532-546. doi: 10.1038/s42255-020-0215-8

An FGFR/AKT/SOX2 Signaling Axis Controls Pancreatic Cancer Stemness

Front Cell Dev Biol 2020 May 7;8:287. doi: 10.3389/fcell.2020.00287

PDGFRα and αSMA mark two distinct mesenchymal cell populations involved in parenchymal and vascular remodeling in pulmonary fibrosis

Am J Physiol Lung Cell Mol Physiol 2020 Apr 1;318(4):L684-L697. doi: 10.1152/ajplung.00128.2019

WNT5a-ROR Signaling Is Essential for Alveologenesis

Cells 2020 Feb 7;9(2):384. doi: 10.3390/cells9020384

Altered proteasome function in right ventricular hypertrophy

Cardiovasc Res 2020 Feb 1;116(2):406-415. doi: 10.1093/cvr/cvz103

WNT/RYK signaling restricts goblet cell differentiation during lung development and repair

PNAS 2019 116 (51) 25697-25706. doi.org/10.1073/pnas.1911071116

Proteasome activator PA200 regulates myofibroblast differentiation

Sci Rep 2019 Oct 23;9(1):15224. doi: 10.1038/s41598-019-51665-0

IRE1 Signaling As a Putative Therapeutic Target in Influenza Virus-induced Pneumonia

Am J Respir Cell Mol Biol 2019 Oct;61(4):537-540. doi: 10.1165/rcmb.2019-0123LE

Verifying Data Integration Configurations for Semantical Correctness and Completeness

Stud Health Technol Inform 2019 Sep 3;267:66-73. doi: 10.3233/SHTI190807

Provenance for Biomedical Ontologies with RDF and Git

Stud Health Technol Inform 2019 Sep 3;267:230-237. doi: 10.3233/SHTI190832

Clinical characteristics of patients with familial idiopathic pulmonary fibrosis (f-IPF)

BMC Pulm Med 2019 Jul 18;19(1):130. doi: 10.1186/s12890-019-0895-6

Regulation and role of the ER stress transcription factor CHOP in alveolar epithelial type-II cells

J Mol Med (Berl) 2019 Jul;97(7):973-990. doi: 10.1007/s00109-019-01787-9

Normal lung development needs self-eating

J Clin Invest 2019 Jun 4;129(7):2658-2659. doi: 10.1172/JCI129442

Adipokine expression in systemic sclerosis lung and gastrointestinal organ involvement

Cytokine 2019 May;117:41-49. doi: 10.1016/j.cyto.2018.11.013

Embryonic mesothelium in motion: a systematic study

Am J Physiol Lung Cell Mol Physiol 2019 May 1;316(5):L764-L766. doi: 10.1152/ajplung.00082.2019

Regulation and role of the ER stress transcription factor Chop in alveolar epithelial type-II cells

J Mol Med (Berl) 2019 Jul;97(7):973-990. doi:10.1007/s00109-019-01787-9

Myh10 deficiency leads to defective extracellular matrix remodeling and pulmonary disease

Nat Commun 2018 Nov 2;9(1):4600. doi: 10.1038/s41467-018-06833-7

Long-term safety of pirfenidone: results of the prospective, observational PASSPORT study

ERJ Open Res 2018 Oct 19;4(4):00084-2018. doi: 10.1183/23120541.00084-2018

The FLORA study: presenting a novel IPF trial design

Lancet Respir Med 2018 Aug;6(8):572-573. doi: 10.1016/S2213-2600(18)30269-8

Activation of the NF-κB pathway alters the phenotype of MSCs in the tracheal aspirates of preterm infants with severe BPD

Am J Physiol Lung Cell Mol Physiol 2018 Jul 1;315(1):L87-L101. doi: 10.1152/ajplung.00505.2017

Low density lipoprotein receptor-related protein 1 couples β1 integrin activation to degradation

Cell Mol Life Sci 2018 May;75(9):1671-1685. doi: 10.1007/s00018-017-2707-6

The Potentials and Caveats of Mesenchymal Stromal Cell-Based Therapies in the Preterm Infant

Stem Cells Int 2018 Apr 8;2018:9652897. doi: 10.1155/2018/9652897

Resident cell lineages are preserved in pulmonary vascular remodeling

J Pathol 2018 Apr;244(4):485-498. doi: 10.1002/path.5044

Phenotypes of organ involvement in sarcoidosis

Eur Respir J 2018 Jan 25;51(1):1700991. doi: 10.1183/13993003.00991-2017

Human lung branching morphogenesis is orchestrated by the spatiotemporal distribution of ACTA2, SOX2, and SOX9

Am J Physiol Lung Cell Mol Physiol 2018 Jan 1;314(1):L144-L149. doi: 10.1152/ajplung.00379.2017

Fgf10-Hippo Epithelial-Mesenchymal Crosstalk Maintains and Recruits Lung Basal Stem Cells

Dev Cell 2017 Oct 9;43(1):48-59.e5. doi: 10.1016/j.devcel.2017.09.003

Senolytic drugs target alveolar epithelial cell function and attenuate experimental lung fibrosis ex vivo

Eur Respir J 2017 Aug 3;50(2):1602367. doi: 10.1183/13993003.02367-2016

Mesenchymal Stem Cells in Fibrotic Disease

Cell Stem Cell 2017 Aug 3;21(2):166-177. doi: 10.1016/j.stem.2017.07.011

MicroRNA-142 is a multifaceted regulator in organogenesis, homeostasis, and disease

Dev Dyn 2017 Apr;246(4):285-290. doi: 10.1002/dvdy.24477

Two-Way Conversion between Lipogenic and Myogenic Fibroblastic Phenotypes Marks the Progression and Resolution of Lung Fibrosis

Cell Stem Cell 2017 Feb 2;20(2):261-273.e3. doi: 10.1016/j.stem.2016.10.004. Epub 2016 Nov 17. Erratum in: Cell Stem Cell. 2017 Apr 6;20(4):571

Correction: Noncanonical WNT-5A signaling impairs endogenous lung repair in COPD

J Exp Med 2017 Feb;214(2):565. doi: 10.1084/jem.2016067501052017c

S2K Guideline for Diagnosis of Idiopathic Pulmonary Fibrosis

Respiration 2021;100(3):238-271. doi: 10.1159/000512315

Using RDF and Git to Realize a Collaborative Metadata Repository

Stud Health Technol Inform 2018;247:556-560

Metadata Import from RDF to i2b2

Stud Health Technol Inform 2018;253:40-44

Pulmonary Hypertension due to Lung Diseases and/or Hypoxia: What Do We Actually Know?

Can Respir J 2017;2017:9598089. doi: 10.1155/2017/9598089

Principal Investigators

Andreas Günther

Prof. Dr. med. Andreas Günther

Justus Liebig University Giessen
Department of Internal Medicine
Klinikstrasse 33; 35392 Giessen

Saverio Bellusci

Prof. Dr. rer. nat. Saverio Bellusci

Justus Liebig University Giessen
Excellence Cluster „Cardiopulmonary System“ 
Aulweg 130, 35392 Giessen

Elie El Agha

Elie El Agha , PhD

Justus Liebig University Giessen, Aulweg 130; 35392 Giessen


Project group

  • Martina Korfei

    Dr. Martina Korfei


  • Cho-Ming Chao

    Dr. Cho-Ming Chao

  • Simone Becker

    Simone Becker


  • Kerstin Goth

    Kerstin Goth