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Department of Infectious Diseases, Respiratory Medicine and Critical Care

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Research

Research

Find more about our research at the Nouailles Lab!

COVID-19 and Single-Cells

Single-cell sequencing and immunology reveal host responses to SARS-CoV-2 and other respiratory pathogens.

Lung Innate Immunity

Orchestration of chemokine expression and neutrophil responses in acute and chronic lung infections.

Lung Epithelial Glycocalyx

Respiratory epithelial glycocalyx and glycoproteins – host defense or entry point for pathogens.

Lung Models for Pneumonia Research

Developing 2D and 3D human lung models, xeno-free culturing and implementation of 3R principles.

Phages – Bacteria-Killing Viruses

Host immunity – innate pulmonary immunity booster or dampener of phage therapy efficacy.

Therapy and Mode of Action

Protective mode of action of immunoglobulin (Trimodulin) therapy in pneumonia. 

Systems Medicine

In vitro, in vivo and real-world data turned into mathematical models of pneumonia and cardiovascular complications thereof.

Single-cell sequencing and immunology reveal host responses to SARS-CoV-2 and other respiratory pathogens.

Project members

Geraldine Nouailles

Peter Pennitz

Ulrike Behrendt

Cengiz Görkeri

Main cooperation partners

Jakob Trimpert and team

Emanuel Wyler/Markus Landthaler and team

Holger Kirsten/Markus Scholz and team

Samantha Praktiknjo and team

Michael Mülleder and team

Achim Gruber and team

Christine Goffinet and team

…many more

Publications

Pennitz P, Goekeri C, Trimpert J, Wyler E, Ebenig A, Weissfuss C, Mühlebach MD, Witzenrath M, Nouailles G. Protocol to dissociate healthy and infected murine- and hamster-derived lung tissue for single-cell transcriptome analysis. STAR Protoc. 2022 Dec 20;4(1):101957

Nouailles, G., Adler, J. M., Pennitz, P., Peidli, S., Alves, G. T., Baumgart, M., Bushe, J., Voss, A., Langenhagen, A., Pott, F., Kazmierski, J., Goekeri, C., Simmons, S., Xing, N., Langner, C., Vidal, R. M., Abdelgawad, A., Herwig, S., Cichon, G., . . . Trimpert, J. (2022). A live attenuated vaccine confers superior mucosal and systemic immunity to SARS-CoV-2 variants. bioRxiv, 2022.2005.2016.492138.

Pennitz P, Kirsten H, Friedrich VD, Wyler E, Goekeri C, Obermayer B, Heinz GA, Mashreghi MF, Büttner M, Trimpert J, Landthaler M, Suttorp N, Hocke AC, Hippenstiel S, Tönnies M, Scholz M, Kuebler WM, Witzenrath M, Hoenzke K, Nouailles G. A pulmonologist’s guide to perform and analyse cross-species single lung cell transcriptomics. Eur Respir Rev. 2022 Jul 27;31(165):220056.

Wyler E, Adler JM, Eschke K, Teixeira Alves G, Peidli S, Pott F, Kazmierski J, Michalick L, Kershaw O, Bushe J, Andreotti S, Pennitz P, Abdelgawad A, Postmus D, Goffinet C, Kreye J, Reincke SM, Prüss H, Blüthgen N, Gruber AD, Kuebler WM, Witzenrath M, Landthaler M, Nouailles G, Trimpert J. Key benefits of dexamethasone and antibody treatment in COVID-19 hamster models revealed by single-cell transcriptomics. Mol Ther. 2022 May 4;30(5):1952-1965.

Nouailles G, Wyler E, Pennitz P, Postmus D, Vladimirova D, Kazmierski J, Pott F, Dietert K, Muelleder M, Farztdinov V, Obermayer B, Wienhold SM, Andreotti S, Hoefler T, Sawitzki B, Drosten C, Sander LE, Suttorp N, Ralser M, Beule D, Gruber AD, Goffinet C, Landthaler M, Trimpert J, Witzenrath M. Temporal omics analysis in Syrian hamsters unravel cellular effector responses to moderate COVID-19. Nat Commun. 2021 Aug 11;12(1):4869.

Ebenig A, Muraleedharan S, Kazmierski J, Todt D, Auste A, Anzaghe M, Gömer A, Postmus D, Gogesch P, Niles M, Plesker R, Miskey C, Gellhorn Serra M, Breithaupt A, Hörner C, Kruip C, Ehmann R, Ivics Z, Waibler Z, Pfaender S, Wyler E, Landthaler M, Kupke A, Nouailles G, Goffinet C, Brown RJP, Mühlebach MD. Vaccine-associated enhanced respiratory pathology in COVID-19 hamsters after TH2-biased immunization. Cell Rep. 2022 Aug 16;40(7):111214.

Andreotti S, Altmüller J, Quedenau C, Borodina T, Nouailles G, Teixeira Alves LG, Landthaler M, Bieniara M, Trimpert J, Wyler E. De Novo-Whole Genome Assembly of the Roborovski Dwarf Hamster (Phodopus roborovskii) Genome: An Animal Model for Severe/Critical COVID-19. Genome Biol Evol. 2022 Jul 2;14(7):evac100.

Conference Papers

SCOG Conference “Single Cell Omics in Clinical Applications”, 07 – 09.11.2022, Bonn.

Pennitz P *, Friedrich VD *, Wyler E, Adler JM, Postmus D, Andreotti S, Teixeira-Alves LG, Kazmierski J, Pott F, Hoefler T, Goekeri C, Landthaler M, Goffinet C, Trimpert J, Scholz M, Witzenrath M, Kirsten H#, Nouailles G#. Interspecies analysis to dissect cellular transcriptomic signatures of humans and hamsters in COVID-19.

21st International Conference on Systems Biology, 08.-12.10.2022, Berlin.

Pennitz P*, Kirsten H*, Friedrich VD, Wyler E, Goekeri C, Obermayer B, Heinz GA, Mashreghi MF, Büttner M, Trimpert J, Landthaler M, Suttorp N, Hocke AC, Hippenstiel S, Tönnies M, Scholz M, Kuebler WM, Witzenrath M, Hoenzke K, Nouailles G. Integrational approaches for cross-species analysis of lung pathologies at single-cell resolution.

e:Med Meeting 2021, 20 – 22.09.2021, online.

Pennitz P, Kirsten H, Goekeri C, Behrendt U, Gutbier B, Heinz G, Mashreghi MF, Wienhold SM, Witzenrath M, Scholz M, Nouailles G. Single-cell RNA-seq for a murine pneumonia lung atlas improving pathomechanistical understanding of community acquired pneumonia.

Project links

Wie ein altbekannter Wirkstoff zum Gamechanger werden kann (Gemeinsame Pressemitteilung von Charité, MDC und FU Berlin, 13.04.2022)

Modell als Grundlage neuer therapeutischer Ansätze (Gemeinsame Pressemitteilung der Charité, des MDC und der FU Berlin, 11.08.2021).

Transregio SFB-TR 84 “Innate Immunity of the Lung: Mechanisms of Pathogen Attack and Host Defence in Pneumonia“

Press Releases

Impfung per Nasenspray könnte Pandemie beenden (Berliner Zeitung, 18.05.2022)

Impfung über Nasenspray: Können nasale Lebendimpfstoffe die Pandemie beenden, Herr Wyler? (Tagesspiegel, 23.05.2022)

Corona-Impfung per Nasenspray: Schnief und Schluss (Zeit-Online, 19.05.2022)

Lebendimpfstoff aus Berlin erzeugt Schleimhautimmunität (Spektrum.de, 18.05.2022)

Nasale Corona-Impfstoffe: Hoffnung auf sterile Immunität (Deutschlandfunk, 18.05.2022)

sCPD9: a SARS-CoV-2 nasal vaccine candidate that may have superior efficacy (News Medical, Life Science, 19.05.2022)

Neues Nasenspray aus Berlin soll besser als RNA-Impfung sein (mdr.de, 19.05.2022)

Spray könnte besser wirken als Spritze (blick.ch, 20.05.2022)

Corona-Impfung: Forscher sehen Erfolge im Tierversuch (sueddeutsche.de, 18.05.2022)

Orchestration of chemokine expression and neutrophil responses in acute and chronic lung infections.

Project members

Geraldine Nouailles

Cengiz Gökeri

Ulrike Behrendt

Sarah Berger (Alumni)

Main cooperation partners

Anca Dorhoi

Stefan Kaufmann

Sarah Hedtrich and team

Publications

Nouailles G, Dorhoi A, Koch M, Zerrahn J, Weiner J 3rd, Faé KC, Arrey F, Kuhlmann S, Bandermann S, Loewe D, Mollenkopf HJ, Vogelzang A, Meyer-Schwesinger C, Mittrücker HW, McEwen G, Kaufmann SH. CXCL5-secreting pulmonary epithelial cells drive destructive neutrophilic inflammation in tuberculosis. J Clin Invest. 2014 Mar;124(3):1268-82.

Dorhoi A, Iannaccone M, Maertzdorf J, Nouailles G, Weiner J 3rd, Kaufmann SH. Reverse translation in tuberculosis: neutrophils provide clues for understanding development of active disease. Front Immunol. 2014 Feb 5;5:36.

Arrey F, Löwe D, Kuhlmann S, Kaiser P, Moura-Alves P, Krishnamoorthy G, Lozza L, Maertzdorf J, Skrahina T, Skrahina A, Gengenbacher M, Nouailles G*, Kaufmann SHE*. Humanized Mouse Model Mimicking Pathology of Human Tuberculosis for in vivo Evaluation of Drug Regimens. Front Immunol. 2019 Jan 31;10:89. *shared last

Dorhoi A, Iannaccone M, Farinacci M, Faé KC, Schreiber J, Moura-Alves P, Nouailles G, Mollenkopf HJ, Oberbeck-Müller D, Jörg S, Heinemann E, Hahnke K, Löwe D, Del Nonno F, Goletti D, Capparelli R, Kaufmann SH. MicroRNA-223 controls susceptibility to tuberculosis by regulating lung neutrophil recruitment. J Clin Invest. 2013 Nov;123(11):4836-48.

Links

CAPSyS: Systemmedizin der ambulant erworbenen Pneumonie (BMBF)

Projektbeschreibung CAPSys (Universität Leipzig)

The alveolar glycocalyx is a sugar-rich fluid layer that sits above the epithelium in our lungs. Consisting of membrane-anchored and freely floating glycoproteins, glycosaminoglycans and proteoglycans, it is located at a critical position, where oxygen exchange takes place and microbes exert their pathogenicity. As a group, we seek to demonstrate the precise involvement of the epithelial glycocalyx in maintaining normal physiology of the lungs including regulation of barrier permeability and immune cell transmigration. On the flip side, microbes have evolved to utilize sugar-harboring structures as attachment points to initiate their virulence programs. Whether the glycocalyx acts as our friend or foe during microbe-triggered pulmonary inflammation remains to be solved.

Project members

Geraldine Nouailles

Cengiz Gökeri

Alina Nettesheim

Kerstin Linke

Sebastian Schickinger

Main cooperation partners

Martin Witzenrath

Peter Seeberger and team

Wolfgang Kübler and team

 Matthias Ochs and team

Kevin Pagel and team

Publications

Ochs M, Hegermann J, Lopez-Rodriguez E, Timm S, Nouailles G, Matuszak J, Simmons S, Witzenrath M, Kuebler WM. On Top of the Alveolar Epithelium: Surfactant and the Glycocalyx. Int J Mol Sci. 2020 Apr 27;21(9):3075.

Conference Papers

1st International Symposium of the CRC 1449 on „Dynamic hydrogels at biointerfaces“, 06.-07.10.2022, Berlin

Linke K, Goekeri C, Nettesheim A, Behrendt U, Lopez-Rodriguez E, Ochs M, Witzenrath M, and Nouailles G. – Epithelial glycocalyx and bacterial pneumonia.

1st International Symposium of the CRC 1449 on „Dynamic hydrogels at biointerfaces“, 06.-07.10.2022, Berlin

Nettesheim A, Linke K, Behrendt U, Barthel D, Lopez-Rodriguez E, Ochs M, Gorenflos López J L, Hackenberger C P R, Seeberger P H, Witzenrath M, Goekeri C, and Nouailles G. – Characterizing the role of fucosylation in bacterial pneumonia

Project Links

CRC 1449 Dynamic Hydrogels at Biointerfaces

Complete announcement from the Tagesspiegel supplement, issue of 3.10.2022

Developing 2D and 3D human lung models, xeno-free culturing and implementation of 3R principles.

Project members

Geraldine Nouailles

Karen Hoffmann

Cengiz Gökeri

Ulrike Behrendt

Lisa Pfeiffer

Peter Pennitz

Main cooperation partners

Christian Zobel, Werner Wenzel and team

Project-related publications

Hoffmann K, Obermayer B, Hönzke K, Fatykhova D, Demir Z, Löwa A, Alves LGT, Wyler E, Lopez-Rodriguez E, Mieth M, Baumgardt M, Hoppe J, Firsching TC, Tönnies M, Bauer TT, Eggeling S, Tran HL, Schneider P, Neudecker J, Rückert JC, Gruber AD, Ochs M, Landthaler M, Beule D, Suttorp N, Hippenstiel S, Hocke AC, Kessler M. Human alveolar progenitors generate dual lineage bronchioalveolar organoids. Commun Biol. 2022 Aug 25;5(1):875.

Hoffmann K, Berger H, Kulbe H, Thillainadarasan S, Mollenkopf HJ, Zemojtel T, Taube E, Darb-Esfahani S, Mangler M, Sehouli J, Chekerov R, Braicu EI, Meyer TF, Kessler M. Stable expansion of high-grade serous ovarian cancer organoids requires a low-Wnt environment. EMBO J. 2020 Mar 16;39(6):e104013.

Conference Papers

International Conference of the SFB-TR 84, 8. – 10.09.2022, Berlin

Pfeiffer L, Weißfuß C, Behrendt U, Wienhold S, Gutbier B, Krishnamoorthy G, Witzenrath M, Nouailles G, Goekeri C, Pennitz P. – Approaching xeno-free cultivation and utilization of pulmonary pathogens in vitro.

2nd Summer School on „infection Biology“ of the Universitöt Greifswald and FLI, 26. – 28.09.2022, Greifswald

Pfeiffer L, Weißfuß C, Behrendt U, Wienhold S, Gutbier B, Krishnamoorthy G, Witzenrath M, Nouailles G, Goekeri C, Pennitz P. – Approaching xeno-free cultivation of pulmonary pathogens in vitro.

Project Links

https://charite3r.charite.de/

NoVAP Lab Bundeswehr Krankenhaus

Host immunity – booster or dampener of phage therapy efficacy

Project members

Geraldine Nouailles

Chantal Weißfuß

Ulrike Behrendt

Main cooperation partners

Martin Witzenrath

MAPVAP consortium

Project-related publications

Wienhold SM, Brack MC, Nouailles G, Krishnamoorthy G, Korf IHE, Seitz C, Wienecke S, Dietert K, Gurtner C, Kershaw O, Gruber AD, Ross A, Ziehr H, Rohde M, Neudecker J, Lienau J, Suttorp N, Hippenstiel S, Hocke AC, Rohde C, Witzenrath M. Preclinical Assessment of Bacteriophage Therapy against Experimental Acinetobacter baumannii Lung Infection. Viruses. 2021 Dec 24;14(1):33.

Conference Papers

Herbsttagung 2021 of the German Respiratory Society (DGP) Section Cell Biology. 12. – 13. November 2021, Hannover. (shared 1st place)

Weißfuß C, Wienhold S-M, Bürkle M, Gaborieau B, Bushe J, Behrendt U, Bischoff R, Korf I, Wienecke S, Dannheim A,  Ziehr H, Rohde C, Gruber A D, Ricard J-D, Debarbieux L, Witzenrath M, and Nouailles G. – Repetitive exposure to bacteriophage cocktails against multidrug-resistant P. aeruginosa or E. coli does not induce pronounced immunity in naïve mice.

62. Congress of the German Respiratory Society (DGP) Section Cell Biology. 25. – 28. May 2022, Leipzig. (Best of Herbsttagung 2021)

Weißfuß C, Wienhold S-M, Bürkle M, Gaborieau B, Bushe J, Behrendt U, Bischoff R, Korf I, Wienecke S, Dannheim A,  Ziehr H, Rohde C, Gruber A D, Ricard J-D, Debarbieux L, Witzenrath M, and Nouailles G. – Repetitive exposure to bacteriophage cocktails against multidrug-resistant P. aeruginosa or E. coli does not induce pronounced immunity in naïve mice.

Project Links

Combination of in vivo phage therapy data with in silico model highlights key parameters for pneumonia treatment efficacy. Cell Reports. May 2022;39(17).

Project site at the BMBF

Project site at the Institut Pasteur

Protective mode of action of immunoglobulin (Trimodulin) therapy in pneumonia. 

Project members

Geraldine Nouailles

Romina Bischoff

Kerstin Linke

Alexander Taylor (Alumni)

Main cooperation partners

Martin Witzenrath         

 Biotest AG

 Achim Gruber

Project-related publications

Jahn K, Handtke S, Palankar R, Weißmüller S, Nouailles G, Kohler TP, Wesche J, Rohde M, Heinz C, Aschenbrenner AF, Wolff M, Schüttrumpf J, Witzenrath M, Hammerschmidt S, Greinacher A. Pneumolysin induces platelet destruction, not platelet activation, which can be prevented by immunoglobulin preparations in vitro. Blood Adv. 2020 Dec 22;4(24):6315-6326.

Project Links

Description at clinicaltrials.gov

Description at biotest.com

In vitro, in vivo and real-world data turned into mathematical models of pneumonia and cardiovascular complications thereof.

Project members

Geraldine Nouailles

Peter Pennitz

Main cooperation partners

Martin Witzenrath, Markus Brack and team

Markus Scholz and team

CAPSyS consortium

Berlin Hamster consortium

Project-related publications

Wyler E, Adler JM, Eschke K, Teixeira Alves G, Peidli S, Pott F, Kazmierski J, Michalick L, Kershaw O, Bushe J, Andreotti S, Pennitz P, Abdelgawad A, Postmus D, Goffinet C, Kreye J, Reincke SM, Prüss H, Blüthgen N, Gruber AD, Kuebler WM, Witzenrath M, Landthaler M, Nouailles G, Trimpert J. Key benefits of dexamethasone and antibody treatment in COVID-19 hamster models revealed by single-cell transcriptomics. Mol Ther. 2022 May 4;30(5):1952-1965.

Nouailles G, Wyler E, Pennitz P, Postmus D, Vladimirova D, Kazmierski J, Pott F, Dietert K, Muelleder M, Farztdinov V, Obermayer B, Wienhold SM, Andreotti S, Hoefler T, Sawitzki B, Drosten C, Sander LE, Suttorp N, Ralser M, Beule D, Gruber AD, Goffinet C, Landthaler M, Trimpert J, Witzenrath M. Temporal omics analysis in Syrian hamsters unravel cellular effector responses to moderate COVID-19. Nat Commun. 2021 Aug 11;12(1):4869.

Schirm S, Haghikia A, Brack M, Ahnert P, Nouailles G, Suttorp N, Loeffler M, Witzenrath M, Scholz M. A biomathematical model of atherosclerosis in mice. PLoS One. 2022 Aug 3;17(8):e0272079.

Schirm S, Ahnert P, Berger S, Nouailles G, Wienhold SM, Müller-Redetzky H, Suttorp N, Loeffler M, Witzenrath M, Scholz M. A biomathematical model of immune response and barrier function in mice with pneumococcal lung infection. PLoS One. 2020 Dec 3;15(12):e0243147.

Berger S, Goekeri C, Gupta SK, Vera J, Dietert K, Behrendt U, Lienau J, Wienhold SM, Gruber AD, Suttorp N, Witzenrath M, Nouailles G. Delay in antibiotic therapy results in fatal disease outcome in murine pneumococcal pneumonia. Crit Care. 2018 Nov 1;22(1):287.

Schirm S, Ahnert P, Wienhold S, Mueller-Redetzky H, Nouailles-Kursar G, Loeffler M, Witzenrath M, Scholz M. A Biomathematical Model of Pneumococcal Lung Infection and Antibiotic Treatment in Mice. PLoS One. 2016 May 19;11(5):e0156047.

Conference papers

SCOG Conference “Single Cell Omics in Clinical Applications”, 07 – 09.11.2022, Bonn.

Pennitz P *, Friedrich VD *, Wyler E, Adler JM, Postmus D, Andreotti S, Teixeira-Alves LG, Kazmierski J, Pott F, Hoefler T, Goekeri C, Landthaler M, Goffinet C, Trimpert J, Scholz M, Witzenrath M, Kirsten H#, Nouailles G#. Interspecies analysis to dissect cellular transcriptomic signatures of humans and hamsters in COVID-19.

21st International Conference on Systems Biology, 08.-12.10.2022, Berlin.

Pennitz P*, Kirsten H*, Friedrich VD, Wyler E, Goekeri C, Obermayer B, Heinz GA, Mashreghi MF, Büttner M, Trimpert J, Landthaler M, Suttorp N, Hocke AC, Hippenstiel S, Tönnies M, Scholz M, Kuebler WM, Witzenrath M, Hoenzke K, Nouailles G. Integrational approaches for cross-species analysis of lung pathologies at single-cell resolution.

e:Med Meeting 2021, 20 – 22.09.2021, online.

Pennitz P, Kirsten H, Goekeri C, Behrendt U, Gutbier B, Heinz G, Mashreghi MF, Wienhold SM, Witzenrath M, Scholz M, Nouailles G. Single-cell RNA-seq for a murine pneumonia lung atlas improving pathomechanistical understanding of community acquired pneumonia.

Project Links

CAPSyS at the BMBF

CAPSyS Homepage

CAPSyS at Systems Medicine

SYMPATH at Systems Medicine

SYMPATH at the BMBF

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