Visualizing neutrophils in context
Neutrophils are key mediators of the immune response, engaging in both local and systemic communication. They interact with neighbouring cells and distant immune compartments, influencing their lifespan, functional state, and activation. This crosstalk involves diverse molecular classes, including lipids, metabolites, nucleic acids, and peptides and their respective receptors. In the first funding period, we have established a platform that facilitates the analysis of neutrophils in their habitat using state of the art Matrix-assisted Laser Desorption Ionisation Mass Spectrometry Imaging (MALDI-MSI) for the analysis of lipids and multiplex microscopyIn the second funding period, we
will advance in situ molecular profiling of neutrophils and their microenvironment using MALDI-MSI to include metabolites and signalling molecules. Multiplex microscopy is extended to multiplex RNA analysis via FISH. Both spatial methods are complemented by Deep Visual Proteomics (DVP), using laser microdissection combined with low-input liquid chromatography–mass spectrometry (LC-MS) of tissue-derived neutrophils and areas. Finally, we implement single-cell lipidomic and proteomic analyses of both circulating and tissue-resident neutrophils. Thus, this central project provides state-of-the-art imaging modalities and serves as a platform to visualize and analyse context-dependent neutrophil biology.
Team
Publications
Genetic Tool for Specific Tracking of Mature NeutrophilsCao, J.; Yaw, H. P.; Yi, S.; Zhou, Y.; Qin, S.; Wang, Y.; da Costa, R.; Zhang, L.; Wu, D.; Chen, C.; Ng, M.; Kwok, I.; Soehnlein, O.; Chen, X.; Wan, J.; Ng, L. G.
2026 hLife
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Divergent Granulopoiesis at Extramedullary Sites Safeguards Antibacterial Host DefenseSilvestre-Roig, C.; Chevre, R.; Farjia, M.; Bender, A.; Vöcking, L. M.; Richter, M.; Hageb, A.; Suerdieck, V.; Arenas Cerro, F. J.; Braster, Q.; Guzman, M.; Sintes, J.; Sharma, S.; Lemnitzer, P.; Tulotta, C.; Börgeling, Y.; Herrero-Cervera, A.; Flueter, H.; Reinartz Groba, S. N.; Ahern, D.; Osei-Sarpong, C.; Zimmer, R.; Alonso-Gonzalez, N.; Ortega, E.; Lienenklaus, S.; Kalinke, U.; Ludwig, S.; Engel, D. R.; Rosenbauer, F.; Monaco, C.; Dersch, P.; Kibler, A.; Cerutti, A.; Chavakis, T.; Benedito, R.; Hidalgo, A.; Jablonska, J.; Palomino-Segura, M.; Soehnlein, O.
2026 Sci Immunol
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Integrated Single-Cell Mass Spectrometry Imaging and Immunofluorescence Microscopy for Multimodal Characterization of Human Immune CellsBessler, S.; Richter, M.; Schwenzfeier, J.; Reinartz Groba, S. N.; Trebicka, J.; Dreisewerd, K.; Soltwisch, J.; Soehnlein, O.
2026 Anal Chem
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IL-1α Drives a Tumor-Stroma-Neutrophil Axis through Inflammatory Fibroblast Activation in Head and Neck CancerHanschmann, E.-M.; Bruderek, K.; Hofmann-Vega, F.; Schmidt, M.; Budeus, B.; Oberlies, W.; Wei, X.; Richter, M.; Lemm, S.; Szlachetko, J. A.; Ryan, S.; Bader, A.; Daser, A.; Lang, S.; Maier-Begandt, D.; Hussain, T.; Soehnlein, O.; Brandau, S.
2026 bioRxiv
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Mutations in VPS18 Lead to a Neutrophil Maturation Defect Associated with Disturbed Vesicle HomeostasisGao, J.; Bader, A.; Linder, M. I.; Cheng, J.; Richter, M.; Da Costa, R.; Zehrer, A.; Mitt, K.; Popper, B.; Meissner, F.; Wei, X.; De Vega Gómez, E.; Tatematsu, M.; Rohlfs, M.; Frenz-Wiessner, S.; Kiziltug, M.; Somekh, I.; Yacobovich, J.; Steinberg-Shemer, O.; Somech, R.; Soehnlein, O.; Schmid, B.; Klein, C.; Walzog, B.; Maier-Begandt, D.
2026 Cell Death Dis
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Interleukin-1α Alters Megakaryocyte Maturation, Promotes Emperipolesis, and Induces a Distinct Proteomic ProfileKolman, R.; Voß, H.; Bertović, I.; Peradinović, J.; Munitić, I.; Engel, D. R.; Shevchuk, O.; Jurak Begonja, A.
2026 J. Thromb. Haemost
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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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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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G-CSF/NAMPT Signaling Drives Neutrophil Dysfunction and Enhances Bacterial Infection Susceptibility in Cancer PatientsPylaeva, E.; Tollrian, L.; Riedesel, J.; Shevchuk, O.; Thiel, I.; Ozel, I.; Kabankova, N.; Voß, H.; Siebels, B.; Schlüter, H.; Haist, C.; Hanenberg, H.; Mattheis, S.; Kürten, C.; Sperandio, M.; Kehrmann, J.; Engel, D. R.; Lang, S.; Jablonska, J.
2025 Nat Commun
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Architecture of the Neutrophil CompartmentCerezo-Wallis, D.; Rubio-Ponce, A.; Richter, M.; Pitino, E.; Kwok, I.; Marteletto, G.; Guanolema-Coba, A. C.; Shih, C.; Huang, R.-K.; Moraga, A.; Bravo, N. B.; Doré, S.; Callejas, S.; Aragonés, D. G.; Jiménez-Carretero, D.; Martin, D.; Ovadia, S.; Vicanolo, T.; Crainiciuc, G.; Sicilia, J.; Deng, T.; Martin, A.; Zhang, J.; Cuartero, M. I.; Giraldo, D. M.; Garcia-Culebras, A.; Aroca-Crevillen, A.; Martín-Salamanca, S.; Torroja, C.; Ruiz, M.; Ruano, I.; Ng, M. S. F.; Hou, J.; Wang, Y.; Zhang, M.; Pu, J.; Herruzo, A.; Van Oordt, D. C.; Chang, S.; Downie, A. E.; Chen, F.; Graham, A. L.; Gause, W. C.; Fiset, P. O.; Spicer, J. D.; Heyn, H.; Zuriaga, M. A.; Bernal, J. A.; Udalova, I. A.; Moro, M. A.; De Bock, K.; Dopazo, A.; Fuster, J. J.; Sánchez-Cabo, F.; Nieto, J. C.; Calvo, G. F.; Skokowa, J.; Soehnlein, O.; Quail, D. F.; Walsh, L. A.; Ng, L. G.; Hidalgo, A.; Ballesteros, I.
2025 Nature
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Maladaptive Emergency Granulopoiesis Predicts Poor Outcomes in Patients Hospitalized with Decompensated CirrhosisAguilar, F.; Lozano, J. J.; Clària, J.; Groba, S. N. R.; Richter, M.; Jiménez-Gracia, L.; Grange, P. de la; Jolly, A.; Praktiknjo, M.; Sánchez-Garrido, C.; Raposo, E. M. U.; García-Torre, B.; Laleman, W.; Gómez-Cabrero, D.; Palomino-Echeverria, S.; Iglesias, E. H.; Farias, A. Q.; Marciano, S.; Caraceni, P.; Trebicka, J.; Cerutti, A.; Arroyo, V.; Heyn, H.; Nieto, J. C.; Soehnlein, O.; Rautou, P.-E.; Moreau, R.; on behalf of the DECISION Consortium.
2025 J Hepatol
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SCAMP3 Is Essential for Proper Formation and Function of Neutrophil GranulesBader, A.; Gao, J.; Reiter, N.; Siemes, D.; Zehrer, A.; Wei, X.; Hepper, I.; de Vega Gómez, E.; Schmid, B.; Forné, I.; Engel, D. R.; Walzog, B.; Maier-Begandt, D.
2025 J Leukoc Biol
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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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Spatial Biology Using Single-Cell Mass Spectrometry Imaging and Integrated MicroscopyPotthoff, A.; Schwenzfeier, J.; Niehaus, M.; Bessler, S.; Hoffmann, E.; Soehnlein, O.; Höhndorf, J.; Dreisewerd, K.; Soltwisch, J.
2025 Nat Commun
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Effect of Long-Term Mediterranean versus Low-Fat Diet on Neutrophil Count, and Type 2 Diabetes Mellitus Remission in Patients with Coronary Heart Disease: Results from the CORDIOPREV StudyBoughanem, H.; Gutierrez-Mariscal, F. M.; Arenas-de Larriva, A. P.; Torres-Peña, J. D.; Romero-Cabrera, J. L.; Rangel-Zuñiga, O. A.; García-Fernández, H.; Podadera-Herreros, A.; Rodríguez-Cantalejo, F.; Soehnlein, O.; Macias-Gonzalez, M.; Tinahones, F. J.; Yubero Serrano, E. M.; Perez-Martinez, P.; Delgado-Lista, J.; López-Miranda, J.
2025 Nutr Diabetes
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SiglecF+ Neutrophils Link Periodontitis to Impaired Post-Myocardial Infarction RepairBoughanem, H.; Herrero-Cervera, A.; Soehnlein, O.
2025 Eur Heart J
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A Reference Database Enabling In-Depth Proteome and PTM Analysis of Mouse Immune CellsSiemes, D.; Voss, H.; Benvenuti, F.; Simoncello, F.; Kopczynski, D.; Siebels, B.; Schlüter, H.; Kollipara, L.; Sickmann, A.; Engel, D. R.; Shevchuk, O.
2025 Sci Data
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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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Multiomic Analysis Uncovers a Continuous Spectrum of Differentiation and Wnt-MDK-Driven Immune Evasion in HepatoblastomaMünter, D.; de Faria, F. W.; Richter, M.; Aranda-Pardos, I.; Hotfilder, M.; Walter, C.; Paga, E.; Inserte, C.; Albert, T. K.; Roy, R.; Rahman, S.; Riedel, N. C.; Müller, V.; Pascher, A.; Wiebe, K.; Schmid, I.; Vokuhl, C.; Winkler, B.; Jüttner, E.; Vieth, S.; Mücke, U.; Kluiver, T. A.; Peng, W. C.; Rossig, C.; Schlué, J.; Madadi-Sanjani, O.; Sandmann, S.; Hartmann, W.; A-Gonzalez, N.; Soehnlein, O.; Kerl, K.
2025 J Hepatol
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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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Altered shear stress of blood flow causes plasma membrane damage in endothelial cellsRaj, N.; Pan, C.; Starke, A. M.; L. Matos, A. L.; Soehnlein, O.; Gerke, V.
2025 Blood Vessels Thromb Hemost
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β-Glucan Reprograms Neutrophils to Promote Disease Tolerance against Influenza A VirusKhan, N.; Tran, K. A.; Chevre, R.; Locher, V.; Richter, M.; Sun, S.; Sadeghi, M.; Pernet, E.; Herrero-Cervera, A.; Grant, A.; Saif, A.; Downey, J.; Kaufmann, E.; Khader, S. A.; Joubert, P.; Barreiro, L. B.; Yipp, B. G.; Soehnlein, O.; Divangahi, M.
2025 Nat Immunol
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Mediterranean Diet, Neutrophil Count, and Carotid Intima-Media Thickness in Secondary Prevention: The CORDIOPREV StudyBoughanem, H.; Torres-Peña, J. D.; Arenas-de Larriva, A. P.; Romero-Cabrera, J. L.; Gómez-Luna, P.; Martín-Piedra, L.; Rodríguez-Cantalejo, F.; Tinahones, F. J.; Yubero Serrano, E. M.; Soehnlein, O.; Perez-Martinez, P.; Delgado-Lista, J.; López-Miranda, J.
2024 Eur Heart J
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Formyl Peptide Receptor 2 (FPR2) Regulates Dendritic Cell Metabolism and Th17 Cell Differentiation during NeuroinflammationLim, J.-H.; Neuwirth, A.; Chung, K.-J.; Grossklaus, S.; Soehnlein, O.; Hajishengallis, G.; Chavakis, T.
2024 Front Immunol
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Neuro-Immune Crosstalk in Hematopoiesis, Inflammation, and RepairAkinyemi, D. E.; Chevre, R.; Soehnlein, O.
2024 Trends in Immunology
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Targeting Extranuclear Histones to Alleviate Acute and Chronic InflammationNicolaes, G. A. F.; Soehnlein, O.
2024 Trends Pharmacol Sci
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Lack of Formyl-Peptide Receptor 1 Mitigates Atherosclerosis in Hyperlipidemic Mice |
Gasdermin D drives focal Crystalline Thrombotic Microangiopathy by accelerating Immunothrombosis and NecroinflammationWatanabe-Kusunoki, K.; Li, C.; Bandeira Honda, T. S.; Zhao, D.; Kusunoki, Y.; Ku, J.; Long, H.; Klaus, M.; Han, C.; Braun, A.; Mammadova-Bach, E.; Linkermann, A.; Van Avondt, K.; Richter, M.; Soehnlein, O.; Linder, M. I.; Klein, C.; Steiger, S.; Anders, H.-J.
2024 Blood
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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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Scientific Advances in Understanding the Pathogenesis, Diagnosis, and Prevention of Urinary Tract Infection in the Past 10 YearsEngel, D. R.; Wagenlehner, F. M. E.; Shevchuk, O.
2024 Infect Dis Clin North Am
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Beyond association: high neutrophil counts are a causal risk factor for atherosclerotic cardiovascular disease |
Comparative transcriptomic and proteomic signature of lung alveolar macrophages reveals the integrin CD11b as a regulatory hub during pneumococcal pneumonia infectionZec, K.; Thiebes, S.; Bottek, J.; Siemes, D.; Spangenberg, P.; Trieu, D. V.; Kirstein, N.; Subramaniam, N.; Christ, R.; Klein, D.; Jendrossek, V.; Loose, M.; Wagenlehner, F.; Jablonska, J.; Bracht, T.; Sitek, B.; Budeus, B.; Klein-Hitpass, L.; Theegarten, D.; Shevchuk, O.; Engel, D. R.
2023 Front Immunol
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Visualization of Metabolites and Microbes at High Spatial Resolution Using MALDI Mass Spectrometry Imaging and in Situ Fluorescence Labeling.Bourceau, P.; Geier, B.; Suerdieck, V.; Bien, T.; Soltwisch, J.; Dreisewerd, K.; Liebeke, M.
2023 Nat Protoc
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DRANquilizing neutrophil function in chronic liver disease |
Visualization of Differential Cardiolipin Profiles in Murine Retinal Cell Layers by High-Resolution MALDI Mass Spectrometry ImagingBessler, S.; Soltwisch, J.; Dreisewerd, K.
2023 Anal Chem
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The RNA editor ADAR2 promotes immune cell trafficking by enhancing endothelial responses to interleukin-6 during sterile inflammationGatsiou, A.; Tual-Chalot, S.; Napoli, M.; Ortega-Gomez, A.; Regen, T.; Badolia, R.; Cesarini, V.; Garcia-Gonzalez, C.; Chevre, R.; Ciliberti, G.; Silvestre-Roig, C.; Martini, M.; Hoffmann, J.; Hamouche, R.; Visker, J. R.; Diakos, N.; Wietelmann, A.; Silvestris, D. A.; Georgiopoulos, G.; Moshfegh, A.; Schneider, A.; Chen, W.; Guenther, S.; Backs, J.; Kwak, S.; Selzman, C. H.; Stamatelopoulos, K.; Rose-John, S.; Trautwein, C.; Spyridopoulos, I.; Braun, T.; Waisman, A.; Gallo, A.; Drakos, S. G.; Dimmeler, S.; Sperandio, M.; Soehnlein, O.; Stellos, K.
2023 Immunity
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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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The Angiopoietin Receptor Tie2 Is Atheroprotective in Arterial EndotheliumAnisimov, A.; Fang, S.; Hemanthakumar, K. A.; Örd, T.; van Avondt, K.; Chevre, R.; Toropainen, A.; Singha, P.; Gilani, H.; Nguyen, S. D.; Karaman, S.; Korhonen, E. A.; Adams, R. H.; Augustin, H. G.; Öörni, K.; Soehnlein, O.; Kaikkonen, M. U.; Alitalo, K.
2023 Nat Cardiovasc Res
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Time-Restricted Feeding Enhances Early Atherosclerosis in Hypercholesterolemic MicePan, C.; Herrero-Fernandez, B.; Borja Almarcha, C.; Gomez Bris, R.; Zorita, V.; Sáez, A.; Maas, S. L.; Pérez-Olivares, L.; Herrero-Cervera, A.; Lemnitzer, P.; van Avondt, K.; Silvestre-Roig, C.; Gonzalez-Granado, J. M.; Chevre, R.; Soehnlein, O.
2023 Circulation
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Longitudinal in vivo monitoring of atheroprogression in hypercholesterolemic mice using photoacoustic imagingFerraro, B.; Giustetto, P.; Schengel, O.; Weckbach, L.; Maegdefessel, L.; Soehnlein, O.
2023 Thromb Haemost
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Loss of soluble guanylyl cyclase in platelets contributes to atherosclerotic plaque formation and vascular inflammationMauersberger, C.; Sager, H. B.; Wobst, J.; Dang, T. A.; Lambrecht, L.; Koplev, S.; Stroth, M.; Bettaga, N.; Schlossmann, J.; Wunder, F.; Friebe, A.; Björkegren, J. L. M.; Dietz, L.; Maas, S. L.; van der Vorst, E. P. C.; Sandner, P.; Soehnlein, O.; Schunkert, H.; Kessler, T.
2022 Nature Cardiovascular Research
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Neutrophils in aging and aging-related pathologiesVan Avondt, K.; Strecker, J.-K.; Tulotta, C.; Minnerup, J.; Schulz, C.; Soehnlein, O.
2022 Immunol Rev
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AIMing 2 treat atherosclerosis |
Trilateral interaction between innervation, leukocyte, and adventitia: a new driver of atherosclerotic plaque formationSohrabi, Y.; Reinecke, H.; Soehnlein, O.
2022 Signal Transduct Target Ther
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