Organ Dysfunction during Systemic Inflammation

Clinical Research Unit CRU342 – Bridging Basic Science and Clinical Research

Systemic Inflammation and Organ Dysfunction. Serious clinical problems

The Clinical Research Unit CRU342 will identify and investigate the different pathophysiological mechanisms that contribute to the development of this devastating diseases. We target possible interventional strategies in preclinical disease models and conduct clinical studies to enforce clinical translation of the results and to discover avenues of potential therapeutic approaches to combat organ injury during systemic inflammation.

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Team

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Selected Publications

27.01.26

Kessler G, Ulas T, Vogl T, Roth J, Albrecht F, Hansen G, von Kaisenberg CS, Härtel C, Bohnhorst B, Viemann D, Pirr S. S100-alarmins, antenatal corticosteroids and the risk of late-onset sepsis in preterm infants: A prospective cohort study. PLoS One. 2026 Jan 27;21(1):e0341544. doi: 10.1371/journal.pone.0341544. PMID: 41591973; PMCID: PMC12843532.
 

21.01.26

Schreiber A, Ambrosy B, Anhlan D, Bletz S, Mellmann A, Ludwig S. Inhibitors of cellular RSK isoforms exhibit anti-SARS-CoV-2 activity, enhance efficacy of direct-acting antivirals, and suppress emergence of resistance. Drug Resist Updat. Published online January 21, 2026. doi:10.1016/j.drup.2026.101357
 

21.01.26

Oguama M, Lindental P, Clemens RA, Lowell CA, Soehnlein O, Roth J, Bakchoul T, Cappenberg A, Zarbock A. Integrin activation by two independently regulated calcium-mediated pathways is required for neutrophil recruitment. Cell Commun Signal. 2026 Jan 21. doi: 10.1186/s12964-026-02666-w. Epub ahead of print. PMID: 41566499.

26.12.25

Soehnlein O, Döring Y. Un-plexing atherosclerosis: how flow shapes arterial inflammation through PlexinD1. Eur Heart J. 2025 Dec 26:ehaf1039. doi: 10.1093/eurheartj/ehaf1039. Epub ahead of print. PMID: 41451753.

14.12.25

Schreiber A, Oberberg N, Ambrosy B, Rodner F, Kumar S, Caliskan DM, Brunotte L, Beer M, Ludwig S. Influenza H5Nx viruses are susceptible to MEK1/2 inhibition by zapnometinib. Emerg Microbes Infect. 2025 Dec;14(1):2471022. doi: 10.1080/22221751.2025.2471022. Epub 2025 Mar 17. PMID: 39976482; PMCID: PMC11915740.

28.10.25

Formiga RO, Pesenti L, de la Héronnière FC, Ladjemi MZ, Stojkov D, Yousefi S, Frachet P, Krafft L, Tiberio L, Bosisio D, Andrieu M, Many S, Karunanithy V, Bailly K, Dhôte T, Saraceni-Tasso G, Castel M, Rousseau C, Starick MR, da Rocha EL, Lombardi EP, Almeida CJLDR, Ramos ADS, Cunha FQ, Alves-Filho JC, Nóbrega NRC, Gonçalves MR, Queiroz-Junior CM, Lima Batista V, Teixeira MM, Granger V, Chollet-Martin S, Chaisemartin L, Mouthon L, Hosmalin A, Hurtado-Nedelec M, Martin C, Spiller F, Simon HU, Tamassia N, Cassatella MA, Pène F, Vogl T, Burgel PR, Costa VV, Witko-Sarsat V. Cytosolic proliferating cell nuclear antigen (PCNA) orchestrates neutrophil hyperactivation in COVID-19. Proc Natl Acad Sci U S A. 2025 Oct 28;122(43):e2503667122. doi: 10.1073/pnas.2503667122. Epub 2025 Oct 21. PMID: 41118208; PMCID: PMC12582264.
 

14.10.25

Zarbock A, Schöne LM, Kellum JA, Gerss J, Weiss R, Booke H, Meersch M. Impact of propofol or sevoflurane on the renoprotective effect of remote ischaemic preconditioning in cardiac surgery: the HypnoRenalRIP randomised clinical trial. Br J Anaesth. 2025 Oct 14:S0007-0912(25)00632-4. doi: 10.1016/j.bja.2025.08.055. Epub ahead of print. PMID: 41093687.
 

24.09.25

Martin HJ, Beasley JM, Kelestemur E, Sessions Z, Ludwig S, Moorman NJ, Baric R, Muratov EN, Tropsha A. Challenges of broad-spectrum antiviral drug discovery and development for emerging pathogens. Drug Discov Today. 2025 Sep 24:104486. doi: 10.1016/j.drudis.2025.104486. Epub ahead of print. PMID: 41005563.
 

22.09.25

Füll Y, Schüssele LM, Hamza H, Hoffmann H, Bauer M, Stenglein S, Pötz O, Steinhilber A, Anselm V, Delany MW, Van den Brand JMA, Van Amerongen G, De Waal L, Pleschka S, Ludwig S, Planz O. Antiviral and immunomodulatory effect of zapnometinib in animal models and hospitalized COVID-19 patients. Front Immunol. 2025 Sep 22;16:1631721. doi: 10.3389/fimmu.2025.1631721. PMID: 41058679; PMCID: PMC12498288.
 

18.09.25

Berger P, Wilming L, Jürgens R, Minchuk Y, Leußink S, Gandhi S, Walter C, Wind SM, Heider D, Lamparter L, Galic M, Stoll M, Jorch SK, Roth J, Austermann J, Fehler O. PSTPIP1 and pyrin, two key regulators of macrophage differentiation. Eur J Cell Biol. 2025 Sep 18;104(4):151518. doi: 10.1016/j.ejcb.2025.151518. Epub ahead of print. PMID: 40997504.
 

14.09.25

Hussain MT, Austin-Williams S, McCay J, Hayat H, Wright TD, Christoforou M, Ykema E, Perretti M, Cooper D, Margraf A. Comparative Assessment of Whole Organ Tissue Processing Methods for the Isolation of Extracellular Vesicles From Intact Organs. J Extracell Vesicles. 2025 Sep;14(9):e70127. doi: 10.1002/jev2.70127. PMID: 40903824; PMCID: PMC12408365.
 

15.08.25

Hellenthal KEM, Kintrup S, Wirth T, Brabenec L, Cursiefen C, Beulen R, Hollmann K, Lehmann M, Burkard P, Roth J, Schughart K, Klotz L, Rossaint J, Meybohm P, Wagner NM. DPP4 inhibition curbs systemic inflammation. Crit Care. 2025 Aug 15;29(1):359. doi: 10.1186/s13054-025-05599-x. PMID: 40817204; PMCID: PMC12357438.
 

 

12.06.25

Cappenberg A, Oguama M, Richter M, Margraf A, Amini W, Lindental P, Mersmann S, Bardel B, Block H, Vogl T, Soehnlein O, Ley K, Rossaint J, Zarbock A. RhoA GAP Myo9b regulates β2-integrin activity and neutrophil recruitment during murine acute kidney injury. Blood. 2025 Jun 12:blood.2024027583. doi: 10.1182/blood.2024027583. Epub ahead of print. PMID: 40504998.

10.06.25

Amini W, Schemmelmann L, Heming JN, Oguama M, Thomas K, Block H, Lindental P, Bardel B, Margraf A, Soehnlein O, Cappenberg A, Zarbock A. Csk-mediated Src family kinase regulation dampens neutrophil infiltration during pulmonary infection. JCI Insight. 2025 Jun 10:e188323. doi: 10.1172/jci.insight.188323. Epub ahead of print. PMID: 40493407.

03.06.25

Polmann L, Grimm JC, Roth J, Barczyk-Kahlert K. Interferon regulatory factor 8 induces intrinsic functional changes in mature neutrophils. J Leukoc Biol. 2025 Jun 3:qiaf078. doi: 10.1093/jleuko/qiaf078. Epub ahead of print. PMID: 40457627.

24.05.25

Thomas K, Rossaint J, Ludwig N, Mersmann S, Kötting N, Grenzheuser J, Schemmelmann L, Oguama M, Margraf A, Block H, Henke K, Hellenthal K, Mirakaj V, Gerke V, Hansen U, Gäher K, Engelhardt M, Roth J, Eble J, Hub E, Rot A, Alon R, Zarbock A. Alveolar epithelial and vascular CXCR2 mediates transcytosis of CXCL1 in inflamed lungs. Nat Commun. 2025 May 24;16(1):4846. doi: 10.1038/s41467-025-60174-w. PMID: 40413164; PMCID: PMC12103508.

23.05.25

Hunkemöller A, Wirth T, Rovas A, Pavenstädt H, Klotz L, Kümpers P. Changes in immune cell signatures during early infection reflect decoupling of capillary perfusion and glycocalyx dimensions. Front Immunol. 2025 May 23;16:1589959. doi: 10.3389/fimmu.2025.1589959. PMID: 40486505; PMCID: PMC12140986.

15.05.25

Honig N, Teubert C, Lamparter L, Keller MN, Austermann J, Berger P, Schmitz A, Rasch C, Nüsse H, Klingauf J, Erpenbeck L, Roth J, Galic M. Primary human neutrophils and monocytes migrate along endothelial cell boundaries to optimize search efficiency under static in vitro conditions. Biol Open. 2025 May 15;14(5):bio061704. doi: 10.1242/bio.061704. Epub 2025 May 13. PMID: 40357751.

23.04.25

Sowa MA, Wu Y, van Groningen J, Di Y, van den Hurk H, Eble JA, Gibbins JM, García Á, Pollitt AY. High-throughput screen identifies MAS9 as a novel inhibitor of the C-type lectin receptor-2 (CLEC-2)-podoplanin interaction. Br J Pharmacol. 2025 Aug;182(16):3838-3851. doi: 10.1111/bph.70036. Epub 2025 Apr 23. PMID: 40269496.

27.02.25

Soehnlein O, Lutgens E, Döring Y. Distinct inflammatory pathways shape atherosclerosis in different vascular beds. Eur Heart J. 2025 Feb 27:ehaf054. doi: 10.1093/eurheartj/ehaf054. Epub ahead of print. PMID: 40036569.

07.02.25

Schreiber A, Ludwig S. Host-targeted antivirals against SARS-CoV-2 in clinical development – Prospect or disappointment? Antiviral Res. 2025 Mar;235:106101. doi: 10.1016/j.antiviral.2025.106101. Epub 2025 Feb 7. PMID: 39923941.

17.01.25

Niland S, Eble JA. Decoding the MMP14 integrin link: Key player in the secretome landscape. Matrix Biol. 2025 Apr;136:36-51. doi: 10.1016/j.matbio.2025.01.004. Epub 2025 Jan 17. PMID: 39828138.

13.12.24

Raj N, Pan C, Starke AM, Matos ALL, Soehnlein O, Gerke V. Altered shear stress of blood flow causes plasma membrane damage in endothelial cells. Blood Vessel Thromb Hemost. 2024 Dec 13;2(1):100040. doi: 10.1016/j.bvth.2024.100040. PMID: 40766873; PMCID: PMC12320452.

29.11.24

Schughart K, Möller-Kerutt A, Höffken V, Nedvetsky P, Groh AC, Braun DA, Pavenstädt H, Weide T. PALS1-dependent modulations of mRNA profiles in MDCK II cells grown in non-confluent monolayers and three-dimensional cysts. BMC Genom Data. 2024 Nov 29;25(1):102. doi: 10.1186/s12863-024-01284-0. PMID: 39614182; PMCID: PMC11607895.

06.11.24

Hellenthal KEM, Thomas K, Ludwig N, et al. Glutamine modulates neutrophil recruitment and effector functions during sterile inflammation. J Leukoc Biol. Published online November 6, 2024. doi:10.1093/jleuko/qiae243

18.09.24

Pajonczyk D, Sternschulte MF, Soehnlein O, Bermudez M, Raabe CA, Rescher U. Comparative analysis of formyl peptide receptor 1 and formyl peptide receptor 2 reveals shared and preserved signalling profiles. Br J Pharmacol. 2024 Sep 18. doi: 10.1111/bph.17334. Epub ahead of print. PMID: 39294930.

13.09.24

Meersch M, Mayerhöfer T, Joannidis M. Acute kidney injury subphenotyping and personalized medicine. Curr Opin Crit Care. 2024 Dec 1;30(6):555-562. doi: 10.1097/MCC.0000000000001212. Epub 2024 Sep 13. PMID: 39503205.

12.08.24

Kintrup S, Brabenec L, Zurek-Leffers FM, Hellenthal KEM, Cyran L, Meybohm P, Gerke V, Wagner NM. Detection and Evaluation of Procalcitonin Variants As Diagnostic Tools in Systemic Inflammation. Anesth Analg. 2024 Aug 12. doi: 10.1213/ANE.0000000000007170. Epub ahead of print. PMID: 39636188.

18.07.24

Akinyemi DE, Chevre R, Soehnlein O. Neuro-immune crosstalk in hematopoiesis, inflammation, and repair. Trends Immunol. 2024 Aug;45(8):597-608. doi: 10.1016/j.it.2024.06.005. Epub 2024 Jul 18. PMID: 39030115.

08.06.24

Nicolaes GAF, Soehnlein O. Targeting extranuclear histones to alleviate acute and chronic inflammation. Trends Pharmacol Sci. 2024 Jul;45(7):651-662. doi: 10.1016/j.tips.2024.05.008. Epub 2024 Jun 8. PMID: 38853103.

10.04.24

Drost CC, Rovas A, Osiaevi I, Schughart K, Lukasz A, Linke WA, Pavenstädt H, Kümpers P. Interleukin-6 drives endothelial glycocalyx damage in COVID-19 and bacterial sepsis. Angiogenesis. 2024 Apr 10. doi: 10.1007/s10456-024-09916-w. Epub ahead of print.

02.03.24

Schreiber A, Rodner F, Oberberg N, Anhlan D, Bletz S, Mellmann A, Planz O, Ludwig S. The host-targeted antiviral drug Zapnometinib exhibits a high barrier to the development of SARS-CoV-2 resistance. Antiviral Res. 2024 May;225:105840. doi:10.1016/j.antiviral.2024.105840. Epub 2024 Mar 2.

29.01.24

Meersch M, Weiss R, Strauß C, Albert F, Booke H, Forni L, Pittet JF, Kellum JA, Rosner M, Mehta R, Bellomo R, Rosenberger P, Zarbock A; EPIS-AKI Investigators. Acute kidney disease beyond day 7 after major surgery: a secondary analysis of the EPIS-AKI trial. Intensive Care Med. 2024 Feb;50(2):247-257. doi: 10.1007/s00134-023-07314-2. Epub 2024 Jan 29

28.07.23

Zarbock A, Weiss R, Albert F, Rutledge K, Kellum JA, Bellomo R, Grigoryev E, Candela-Toha AM, Demir ZA, Legros V, Rosenberger P, Galán Menéndez P, Garcia Alvarez M, Peng K, Léger M, Khalel W, Orhan-Sungur M, Meersch M; The EPIS-AKI Investigators. Epidemiology of surgery associated acute kidney injury (EPIS-AKI): a prospective international observational multi-center clinical study. Intensive Care Med. 2023 Jul 28. doi: 10.1007/s00134-023-07169-7. Epub ahead of print.

06.02.23

Shirakura K, Baluk P, Nottebaum AF, Ipe U, Peters KG, McDonald DM, Vestweber D. Shear stress control of vascular leaks and atheromas through Tie2 activation by VE-PTP sequestration. EMBO Mol Med. 2023. Feb 6;e16128. doi: 10.15252/emmm.202216128.

06.12.22

Revenstorff J, Ludwig N, Hilger A, Mersmann S, Lehmann M, Grenzheuser JC, Kardell M, Bone J, Kötting NM, Marx NC, Roth J, Vogl T, Rossaint J. Role of S100A8/A9 in Platelet-Neutrophil Complex Formation during Acute Inflammation. Cells. 2022 Dec 6;11(23):3944. doi: 10.3390/cells11233944. 

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