Sepsis and polytrauma - entities with a high prevalence and lethality - are accompanied by a systemic inflammatory response triggered by so-called damage- and pathogen-associated molecular patterns (DAMPs and PAMPs). In this case, the "first cellular line of defense" of the innate immune system, the neutrophil granulocytes, are activated excessively. This often leads to immune dysfunction and subsequently multiorgan failure, which further increases the lethality of patients with sepsis and polytrauma.
We focus on single-cell physiological changes after exposure to various danger signals (e.g. by multiparametric flow cytometry). Within our main focus, we analyse the immune status and the inflammatory response during clinical systemic inflammation, for example in patients with sepsis or after severe injuries, in a precise, reliable and minimally invasive manner. Our main interest is the innate immune response of the first cellular line of defense (e.g. neutrophils). In addition, we aim to understand the interaction of platelets and leukocytes as a major column of the thromboinflammatory response. For this purpose, we perform screening assays of FDA-approved drugs and apply an animal-free alternative for simulating the complex thromboinflammation in human whole blood. Finally, the results are verified in clinical patient cohorts.
Encouragement of young scientists
The Cellular Defense group is actively involved in promoting young scientists. This takes place mainly within the framework of supervised dissertations in the fields of medicine, molecular medicine, biochemistry and biology, biotechnology and others. The success of our students is reflected, for example, in first and co-authorships in publications, awards, as well as active participation in congresses.
Publications
Wohlgemuth L.*, Stratmann A.E.P.*, Münnich F., Bernhard S., Thomaß B.D., Münnich F., Mohamed A.O.K., Mannes M., Schmidt C.Q., Nilsson Ekdahl K., Nilsson B., Fauler M., Föhr K.J., Huber-Lang M., Messerer D.A.C.,2022. Modulation of Neutrophil Activity by Soluble Complement Cleavage Products-An In-Depth Analysis. Cells. https://doi.org/10.3390/cells11203297
Stratmann, A.E.P.*,Wohlgemuth, L.*, Erber M. E., Bernhard S., Hug S., Fauler M., Vidoni L., Mohamed A.O.K., Thomaß B.D., Münnich F., Stukan L., Föhr K.J., Mannes M., Huber-Lang M.S., Messerer D.A.C., 2021. Simultaneous Measurement of Changes in Neutrophil Granulocyte Membrane Potential, Intracellular pH, and Cell Size by Multiparametric Flow Cytometry. Biomedicines. https://doi.org/10.3390/biomedicines9111504
Hug S., Bernhard S., Stratmann A.E.P, Erber M., Wohlgemuth L., Knapp C.L., Bauer J.M., Vidoni L., Fauler M., Föhr K.J., Radermacher P., Hoffmann A., Huber-Lang M., Messerer D.A.C.,2021. Activation of Neutrophil Granulocytes by Platelet-Activating Factor Is Impaired During Experimental Sepsis. Front Immunol. doi.org/10.3389/fimmu.2021.642867
Bernhard S., Hug S., Stratmann A.E.P., Erber M., Vidoni L., Knapp C.L., Thomaß B.D., Fauler M., Nilsson B., Nilsson Ekdahl K., Föhr K., Braun C.K., Wohlgemuth L., Huber-Lang M., Messerer D.A.C., 2021. Interleukin 8 Elicits Rapid Physiological Changes in Neutrophils That Are Altered by Inflammatory Conditions. J Innate Immun. doi.org/10.1159/000514885
Further publications: Lisa Wohlgemuth
Team
The working group was founded in the course of the Clinical Scientist Programme by PD Dr. David Messerer in 2019, who is now the head of the Department of Molecular Diagnostics at the Institute of Clinical Transfusion Medicine and Immunogenetics Ulm. In the following, you will find the theses that were conducted in our research group.
- Joe Sendas, Medical Dissertation, Focus on modulation of neutrophil activity by biotin-beads coated with complement cleavage products
- Timo Westermann, Medical Dissertation, Focus on immunophenotypic analysis of neutrophil granulocytes in patients with DAMP- or PAMP-driven systemic inflammation
- Julia Altvater, Master Thesis, Focus on validation of the pharmacological influence of EMA/FDA approved drugs on neutrophil granulocytes in patients with systemic inflammation
- Hanna Bessler, Medical Dissertation, Focus on immunological changes as an early warning system for Sepsis-Induced Acute Kidney failure (SAKI)
- Pascal Lessing, Medical Dissertation, Focus on functional changes of neutrophil granulocytes in patients during major cardiac surgery
- Dominik Hüsken, Medical Dissertation, Focus on testing flow cytometry-based immunomonitoring in patients undergoing major cardiac surgery
- Alexander Koller, Medical Dissertation, Focus on drug repurposing in sepsis
- Paul Müller, Medical Dissertation, Focus on immune dysfunction in sepsis
- Bertram Thomaß, Medical Dissertation, Focus on analysis of large datasets of immune cells during sepsis and polytrauma
- Simon Lauer, Medical Dissertation, Focus on immune dysfunction in polytrauma
- Laura Stukan, Medical Dissertation, Focus on thromboinflammation in sepsis
- Frederik Münnich, Medical Dissertation, Focus on immune dysfunction in sepsis
- Larissa Höpfer, Medical Dissertation, Focus on neutrophil granulocyte dysfunction in cystic fibrosi
- Adam Mohamed, Medical Dissertation, Focus on ex-vivo modelling of polytrauma
- Alexander Stratmann, Medical Dissertation, Focus on C5a-induced neutrophil granulocyte dysfunction
Alumni
- Christiane Knapp, Medical Dissertation, "Die Rolle des Plättchenaktivierenden Faktors (PAF) bei der thromboinflammatorischen Aktivität neutrophiler Granulozyten"
- Andrea Tuchan, Master Thesis, "Drug repurposing in sepsis"
- Finn Münnich, Mathematics research assistant
- Stefan Bernhard, Medical Dissertation, Dissertation: "Interleukin 8 induced changes in the intracellular pH of neutrophil granulocytes", Publikation: "Interleukin 8 Elicits Rapid Physiological Changes in Neutrophils That Are Altered by Inflammatory Conditions"
- Stefan Hug, Medical Dissertation, Dissertation: "Experimental sepsis impairs neutrophil granulocyte activation by platelet-activating factor", Publikation: "Activation of Neutrophil Granulocytes by Platelet-Activating Factor Is Impaired During Experimental Sepsis"
- Lukas Keßling, Medical Dissertation, "Judgement agreement between student and medical examiners"
- Rebecca Traut, Master Thesis, "Monitoring of Thromboinflammation as Immunomonitoring Method in Experimental and Clinical Sepsis"
- Leonard Schöbel, Master Thesis, "The Cellular Response capacity of neutrophils as a novel immunomonitoring method – a proof of concept study"
- Laura Vidoni, Master Thesis, "Definition of a sepsis-like immunophenotype of neutrophil granulocytes in a human ex vivo whole blood model"
- Maike Erber, Master Thesis, "Electrophysiological phenotype of neutrophil granulocytes during systemic inflammation"
- Bertram Thomaß, Bachelor Thesis, "Development of an analysis method for the distribution patterns of human granulocytes in flow cytometry"
Collaborations
- BioLAGO e.V. – The health network
- Dr. E. Chteinberg (Institute of Human Genetics, University Medical Center Ulm)
- Prof. Dr. F. Gebhard (Department of Orthopedic Trauma, Hand-, Plastic- and Reconstructive Surgery, University Medical Center Ulm)
- Dr. B. Hagemann (Institute for Medical Microbiology and Hygiene, University Medical Center Ulm)
- Prof. Dr. A. Liebold (Department of Cardiothoracic and Vascular Surgery, University Medical Center Ulm)
- PD Dr. D. Messerer (Department of Molecular Diagnostics, Molecular Therapy and Experimental Transplantation, Institute of Clinical Transfusion Medicine and Immunogenetics Ulm)
- Prof. Dr. B. Nilsson (Department of Immunology, Genetics and Pathology, University Uppsala, Schweden)
- Prof. Dr. K. Nilsson Ekdahl (Department of Immunology, Genetics and Pathology, University Uppsala, Linnæus Center of Biomaterials Chemistry, Schweden)
- PD Dr. C. Schmidt (Institute of Pharmacology of Natural Products and Clinical Pharmacology, Ulm University)
- Prof. Dr. M. Weiß, Prof. Dr. E. Barth (Department of Anaesthesiology and Intensive Care Medicine, University Medical Center Ulm)