Role of CD177 for neutrophil function post ischemia
This project investigates the role of the neutrophil surface molecule CD177 in ischemic stroke. Our work in the first funding period revealed that CD177+ and CD177– neutrophils represent stable and molecularly distinct subsets in humans. We also showed that low numbers or the complete absence of CD177+ neutrophils are associated with poorer recovery after clinical stroke. The planned work aims to molecularly understand how these neutrophil subsets interact with microglia and brain endothelial cells, and how this influences stroke outcome. Four main objectives are pursued: identification of CD177 binding partners on microglia using genetic, proteomic, and structural modelling approaches; in-depth analysis of the origin and functional characteristics of CD177+ and CD177– neutrophils, including subtype-specific surface markers and their clinical relevance; characterization of neutrophil interactions in ischemic brain compartments and the impact of CD177 deficiency in mice; and evaluation of how CD177+ and CD177– neutrophils affect endothelial function, inflammation, and repair. The work combines clinical cohorts, mouse models, proteomics, advanced imaging and in vitro organoid systems to define neutrophil-centred CD177-mediated mechanisms in stroke.
Team
Publications
CD177 Expression on Neutrophils Predicts Ischemic Stroke Outcome in HumansGronewold, J.; Hagemann, N.; Zhang, Y.; Jung, M.; Fleischer, M.; Mohamud Yusuf, A.; Li, A.; Wang, C.; Dzyubenko, E.; Scholtysik, R.; Klein-Hitpass, L.; Kraus, A.; Tuz, A. A.; Singh, V.; Frank, B.; Mönig, A.; Giese, A.; Graser, C.; Niklas, E. M.; Da Silva Rafael, M.; Nanthagopal, M.; Neumann, J.; Kufner, A.; Liman, T. G.; Liu, Y.; Minnerup, J.; Klotz, L.; Giebel, B.; Tertel, T.; Endres, M.; Hermann, D. M.; Gunzer, M.
2026 Stroke
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SARS-CoV-2 Peptide Fragments Selectively Dysregulate Specific Immune Cell Populations via Gaussian Curvature TargetingZhang, Y.; Silvestre-Roig, C.; Fu, H.; Alimohamadi, H.; Mandal, T.; Chen, J. W.; Luo, E. W.-C.; Anda, J. D.; Linard Matos, A. L.; Richter, M.; Mennella, A.; Lee, H.; Chan, L. C.; Wang, Y.; Wang, N.; Wang, H.; Wang, X.; Lee, C. K.; Ghosh, S.; Matsui, T.; Weiss, T. M.; Guo, T.; Zhang, M.; Li, D.; Wolfgang, M. C.; Hagan, R. S.; Li, M. M. H.; Gunzer, M.; Sickmann, A.; Frasca, L.; Yeaman, M. R.; Lande, R.; Cui, Q.; Soehnlein, O.; Wong, G. C. L.
2026 Proc Natl Acad Sci
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Astrocytic PIEZO Activation by Heartbeat Sound Promotes Extracellular Matrix and Maturation in Human Brain OrganoidsFerreira Oliveira, A.; Rambow, F.; Makhzami, S.; Nikolaev, Y. A.; Novak, A.; Shevchuk, O.; Voss, H.; Engel, D. R.; Schult, P. A.; Pillath-Eilers, M.; Kaltwasser, B.; Brockmeier, U.; Kleinschnitz, C.; Hermann, D. M.; Dzyubenko, E.
2025 bioRxiv
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The Nuclear Receptor NR4A1 Serves as a Neutrophil-Intrinsic Regulator Mitigating Stroke SeverityStrecker, J.-K.; Schmidt, Y.; Liebmann, M.; Walter, C.; Roth, S.; Aleth, H.; Börsch, A.-L.; Schmidt-Pogoda, A.; Beuker, C.; Yusuf, A. M.; Revenstorff, J.; Osei-Sarpong, C.; Krafft, L.; Schwarze, A.-S.; Heming, M.; Richter, M.; Kuhlmann, T.; Hucke, S.; Heming, J.-N.; Hansen, U.; Hagemann, N.; Bader, A.; Gao, J.; Walzog, B.; Maier-Begandt, D.; Chevre, R.; Hanschmann, E.-M.; Lücke, M.; Sommer, C.; Hermann, D. M.; Roth, J.; Thomas, C.; Meyer Zu Hörste, G.; Gunzer, M.; Vogl, T.; Zarbock, A.; Rosenbauer, F.; Silvestre-Roig, C.; Söhnlein, O.; Klotz, L.; Minnerup, J.
2025 bioRxiv
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Neutrophil Progenitor Mobilization Is a Distinct Feature of STEMI and Predicts SurvivalRichter, M.; Von Göwels*, J.; Fähndrich*, M.; Fernandez*, C. L.; Grohn*, K.; Schwarz, D.; Lang, A.; Polzin, A.; Farinola, L.; Gosh, S.; Groba, S. R.; Heming, J.-N.; Aleth, H.; Rübsamen, N.; Radecke, T.; Rosenbauer, F.; Sickmann, A.; Karch, A.; Zarbock, A.; Minnerup, J.; Sindermann, J.; Bender, A.; Rossaint, J.; Ormanns, S.; Gunzer, M.; Reinecke, H.; Makowski, L.; Jung, C.; Silvestre-Roig, C.; Kelm, M.; Gerdes, N.; Chevre, R.; Lange, S.; Soehnlein, O.
2025 Research Square
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TSP1/TGF-Β1 Drives Arachidonic Acid Metabolism to Orchestrate Neutrophil SwarmingWidera, L.; Spangenberg, P.; Siemes, D.; Bessler, S.; Bottek, J.; Voss, H.; Novak, A.; Hueser, D.; Richter, M.; Potthoff, A.; Siebels, B.; Moritz, M.; Gocke, A.; Thiebes, S.; Tautges, S.; Chavakis, T.; Jablonska, J.; Lämmermann, T.; Gunzer, M.; Schlüter, H.; Hahn, J.; Grüneboom, A.; Soehnlein, O.; Dreisewerd, K.; Soltwisch, J.; Shevchuk, O.; Engel, D. R.
2025 bioRxiv
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Neutrophil-Specific Targeting of STAT3 Impairs Tumor Progression via the Expansion of Cytotoxic CD8+ T CellsOzel, I.; Sha, G.; Będzińska, A.; Pylaeva, E.; Naumova, Y.; Thiel, I.; Antczak, J.; Squire, A.; Gunzer, M.; Zelinskyy, G.; Kürten, C.; Lang, S.; Silvestre-Roig, C.; Kortylewski, M.; Granot, Z.; Jablonska, J.
2025 Signal Transduct Target Ther
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Implicit Neural Image Field for Biological Microscopy Image CompressionDai, G.; Zhang, R.; Wuwu, Q.; Tseng, C.-C.; Zhou, Y.; Wang, S.; Qian, S.; Lu, M.; Tuz, A. A.; Gunzer, M.; Huang, T.; Chen, J.; Zhang, S.
2025 Nat Comput Sci
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Deactivation of Ceramide de Novo Synthesis Induces Cerebral Angiogenesis and Microvascular Remodeling Post-Ischemia/Reperfusion in Mice via Mechanisms Not Predominated by Extracellular VesiclesMohamud Yusuf, A.; Hussner, T.; Li, A.; Hagemann, N.; Hornemann, T.; Tertel, T.; Brockmeier, U.; Schumacher, F.; Kleuser, B.; Giebel, B.; Gunzer, M.; Gulbins, E.; Hermann, D. M.
2025 J Cereb Blood Flow Metab
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Hypoxic-Ischemic Brain Injury in Neonatal Mice Sequentially Recruits Neutrophils with Dichotomous Phenotype and FunctionRichter, M.; Diesterbeck, E.; Pylaeva, E.; Labusek, N.; Köster, C.; Nagel, D.; Karsch, L.; Fischer, A. J.; Sous, M.; Jung, M.; Chevre, R.; Hagemann, N.; Andersson, E. A.; Ek, C. J.; Singh, V.; Hermann, D. M.; Gunzer, M.; Jablonska, J.; Felderhoff-Müser, U.; Bendix, I.; Soehnlein, O.; Herz, J.
2025 Nat Commun
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Autophagy Hub-Protein P62 Orchestrates Oxidative, Endoplasmic Reticulum Stress, and Inflammatory Responses Post-Ischemia, Exacerbating Stroke OutcomeQuan, X.; Yang, Y.; Liu, X.; Kaltwasser, B.; Pillath-Eilers, M.; Walkenfort, B.; Voortmann, S.; Mohamud Yusuf, A.; Hagemann, N.; Wang, C.; Hasenberg, M.; Hermann, D. M.; Brockmeier, U.
2025 Redox Biology
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Gut Microbiota Deficiency Reduces Neutrophil Activation and Is Protective after Ischemic StrokeTuz, A. A.; Ghosh, S.; Karsch, L.; Antler, M.; Lakovic, V.; Lohmann, S.; Lehmann, A. H.; Beer, A.; Nagel, D.; Jung, M.; Hörenbaum, N.; Kaygusuz, V.; Qefalia, A.; Alshaar, B.; Amookazemi, N.; Bolsega, S.; Basic, M.; Siveke, J. T.; Heiles, S.; Grüneboom, A.; Lueong, S.; Herz, J.; Sickmann, A.; Hagemann, N.; Hasenberg, A.; Hermann, D. M.; Gunzer, M.; Singh, V.
2025 J Neuroinflammation
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Risk beyond neutropenia: insights into neutrophil migration from newly diagnosed AML until late after allogeneic stem cell transplantationCibir, Z.; Beer, A.; Kraus, A.; Pillibeit, A.; Bludau, D.; Abdulla, H.; Neuendorff, N. R.; Sonneck, J.; Kowitz, L.; Riese, S.; Tuz, A. A.; Chen, J.; Cherneha, M.; Beelen, D. W.; Reinhardt, H. C.; Gunzer, M.; Turki, A. T.
2025 J Leukoc Biol
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Inhibition of Tumour Necrosis Factor Alpha by Etanercept Attenuates Shiga Toxin-Induced Brain PathologyChrist, R.; Siemes, D.; Zhao, S.; Widera, L.; Spangenberg, P.; Lill, J.; Thiebes, S.; Bottek, J.; Borgards, L.; Pinho, A. G.; Silva, N. A.; Monteiro, S.; Jorch, S. K.; Gunzer, M.; Siebels, B.; Voss, H.; Schlüter, H.; Shevchuk, O.; Chen, J.; Engel, D. R.
2025 J Neuroinflammation
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msiFlow: automated workflows for reproducible and scalable multimodal mass spectrometry imaging and microscopy data analysisSpangenberg, P.; Bessler, S.; Widera, L.; Bottek, J.; Richter, M.; Thiebes, S.; Siemes, D.; Krauß, S. D.; Migas, L. G.; Kasarla, S. S.; Phapale, P.; Kleesiek, J.; Führer, D.; Moeller, L. C.; Heuer, H.; Van de Plas, R.; Gunzer, M.; Soehnlein, O.; Soltwisch, J.; Shevchuk, O.; Dreisewerd, K.; Engel, D. R.
2025 Nat Commun
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Hypercholesterolemia triggers innate immune imbalance and transforms brain infarcts after ischemic strokeTuz, A. A.; Hoerenbaum, N.; Ulusoy, Ö.; Ahmadi, A.; Gerlach, A.; Beer, A.; Kraus, A.; Hasenberg, A.; Hagemann, N.; Hermann, D. M.; Gunzer, M.; Singh, V.
2025 Front. Immunol.
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Proteomic Characterization of 1,000 Human and Murine Neutrophils Freshly Isolated from Blood and Sites of Sterile InflammationGhosh, S.; Tuz, A. A.; Stenzel, M.; Singh, V.; Richter, M.; Soehnlein, O.; Lange, E.; Heyer, R.; Cibir, Z.; Beer, A.; Jung, M.; Nagel, D.; Hermann, D. M.; Hasenberg, A.; Grüneboom, A.; Sickmann, A.; Gunzer, M.
2024 Mol Cell Proteomics
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Extracellular vesicles set the stage for brain plasticity and recovery by multimodal signallingHermann, D. M.; Peruzzotti-Jametti, L.; Giebel, B.; Pluchino, S.
2024 Brain
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Arterial Specification Precedes Microvascular Restitution in the Peri-Infarct Cortex That Is Driven by Small MicrovesselsHagemann, N.; Qi, Y.; Mohamud Yusuf, A.; Li, A.; Zhang, X.; Spangenberg, P.; Squire, A.; Doeppner, T. R.; Jin, F.; Zhao, S.; Chen, J.; Mosig, A.; Gunzer, M.; Hermann, D. M.
2024 J Cereb Blood Flow Metab
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Stroke and Myocardial Infarction Induce Neutrophil Extracellular Trap Release Disrupting Lymphoid Organ Structure and Immunoglobulin SecretionTuz, A. A.; Ghosh, S.; Karsch, L.; Ttoouli, D.; Sata, S. P.; Ulusoy, Ö.; Kraus, A.; Hoerenbaum, N.; Wolf, J.-N.; Lohmann, S.; Zwirnlein, F.; Kaygusuz, V.; Lakovic, V.; Tummes, H.-L.; Beer, A.; Gallert, M.; Thiebes, S.; Qefalia, A.; Cibir, Z.; Antler, M.; Korste, S.; Haj Yehia, E.; Michel, L.; Rassaf, T.; Kaltwasser, B.; Abdelrahman, H.; Mohamud Yusuf, A.; Wang, C.; Yin, D.; Haeusler, L.; Lueong, S.; Richter, M.; Engel, D. R.; Stenzel, M.; Soehnlein, O.; Frank, B.; Solo-Nomenjanahary, M.; Ho-Tin-Noé, B.; Siveke, J. T.; Totzeck, M.; Hoffmann, D.; Grüneboom, A.; Hagemann, N.; Hasenberg, A.; Desilles, J.-P.; Mazighi, M.; Sickmann, A.; Chen, J.; Hermann, D. M.; Gunzer, M.; Singh, V.
2024 Nat Cardiovasc Res
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ComplexEye: a multi-lens array microscope for high-throughput cell migration analysisCibir, Z.; Hassel, J.; Sonneck, J.; Kowitz, L.; Beer, A.; Kraus, A.; Hallekamp, G.; Rosenkranz, M.; Raffelberg, P.; Olfen, S.; Smilowski, K.; Burkard, R.; Helfrich, I.; Tuz, A. A.; Singh, V.; Ghosh, S.; Sickmann, A.; Klebl, A.-K.; Eickhoff, J. E.; Klebl, B.; Seidl, K.; Chen, J.; Grabmaier, A.; Viga, R.; Gunzer, M.
2024 Nat Commun
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Microvascular Network Remodeling in the Ischemic Mouse Brain Defined by Light Sheet MicroscopyHagemann, N.; Qi, Y.; Mohamud Yusuf, A.; Li, A.; Squire, A.; Tertel, T.; Giebel, B.; Ludewig, P.; Spangenberg, P.; Chen, J.; Mosig, A.; Gunzer, M.; Hermann, D. M.
2024 Arterioscler Thromb Vasc Biol
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Modulating microglia to enhance neuroplasticity for restoring brain function after strokeLiu, Z.; Hermann, D. M.; Dzyubenko, E.; Cao, G.; Cao, X.
2023 Front Cell Neurosci
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Structural changes in perineuronal nets and their perforating GABAergic synapses precede motor coordination recovery post strokeDzyubenko, E.; Willig, K. I.; Yin, D.; Sardari, M.; Tokmak, E.; Labus, P.; Schmermund, B.; Hermann, D. M.
2023 J Biomed Sci
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Neural precursor cell delivery induces acute post-ischemic cerebroprotection, but fails to promote long-term stroke recovery in hyperlipidemic mice due to mechanisms that include pro-inflammatory responses associated with brain hemorrhagesYin, D.; Wang, C.; Qi, Y.; Wang, Y.-C.; Hagemann, N.; Mohamud Yusuf, A.; Dzyubenko, E.; Kaltwasser, B.; Tertel, T.; Giebel, B.; Gunzer, M.; Popa-Wagner, A.; Doeppner, T. R.; Hermann, D. M.
2023 J Neuroinflammation
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ComplexEye: a multi-lens array microscope for high-throughput embedded immune cell migration analysisCibir, Z.; Hassel, J.; Sonneck, J.; Kowitz, L.; Beer, A.; Kraus, A.; Hallekamp, G.; Rosenkranz, M.; Raffelberg, P.; Olfen, S.; Smilowski, K.; Burkard, R.; Helfrich, I.; Tuz, A. A.; Singh, V.; Ghosh, S.; Sickmann, A.; Klebl, A.-K.; Eickhoff, J. E.; Klebl, B.; Seidl, K.; Chen, J.; Grabmaier, A.; Viga, R.; Gunzer, M.
2023 Nat Rev Immunol
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Externalized Histones Fuel Pulmonary Fibrosis via a Platelet-Macrophage Circuit of TGFβ1 and IL-27Riehl, D. R.; Sharma, A.; Roewe, J.; Murke, F.; Ruppert, C.; Eming, S. A.; Bopp, T.; Kleinert, H.; Radsak, M. P.; Colucci, G.; Subramaniam, S.; Reinhardt, C.; Giebel, B.; Prinz, I.; Guenther, A.; Strand, D.; Gunzer, M.; Waisman, A.; Ward, P. A.; Ruf, W.; Schäfer, K.; Bosmann, M.
2023 Proc Natl Acad Sci
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Rapid and Fully Automated Blood Vasculature Analysis in 3D Light-Sheet Image Volumes of Different OrgansSpangenberg, P.; Hagemann, N.; Squire, A.; Förster, N.; Krauß, S. D.; Qi, Y.; Yusuf, A. M.; Wang, J.; Grüneboom, A.; Kowitz, L.; Korste, S.; Totzeck, M.; Cibir, Z.; Tuz, A. A.; Singh, V.; Siemes, D.; Struensee, L.; Engel, D. R.; Ludewig, P.; Nascentes Melo, L. M.; Helfrich, I.; Chen, J.; Gunzer, M.; Hermann, D. M.; Mosig, A.
2023 Cell Reports Methods
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A20 and the Noncanonical NF-κB Pathway Are Key Regulators of Neutrophil Recruitment during Fetal OntogenyRohwedder, I.; Wackerbarth, L. M.; Heinig, K.; Ballweg, A.; Altstätter, J.; Ripphahn, M.; Nussbaum, C.; Salvermoser, M.; Bierschenk, S.; Straub, T.; Gunzer, M.; Schmidt-Supprian, M.; Kolben, T.; Schulz, C.; Ma, A.; Walzog, B.; Heinig, M.; Sperandio, M.
2023 JCI Insight
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During Early Stages of Cancer, Neutrophils Initiate Anti-Tumor Immune Responses in Tumor-Draining Lymph NodesPylaeva, E.; Korschunow, G.; Spyra, I.; Bordbari, S.; Siakaeva, E.; Ozel, I.; Domnich, M.; Squire, A.; Hasenberg, A.; Thangavelu, K.; Hussain, T.; Goetz, M.; Lang, K. S.; Gunzer, M.; Hansen, W.; Buer, J.; Bankfalvi, A.; Lang, S.; Jablonska, J.
2022 Cell Reports
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Pathological neutrophil migration predicts adverse outcomes in hospitalized patients with liver cirrhosisLanger, M.-M.; Sichelschmidt, S.; Bauschen, A.; Bornemann, L.; Guckenbiehl, S.; Gunzer, M.; Lange, C. M.
2022 Liver International
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Ischemic stroke and concomitant gastrointestinal complications- a fatal combination for patient recoveryTuz, A. A.; Hasenberg, A.; Hermann, D. M.; Gunzer, M.; Singh, V.
2022 Front Immunol
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