Juniorgroup "Experimental Research"

Prof. Markus Bosmann, MD
Leader Juniorgroup "Experimental Research"

Sepsis and acute lung injury (ALI, ARDS) are life-threatening diseases in intensive care medicine with an estimated 150,000 cases per year in Germany. Patients with a weakened immune system have an increased risk for infections (e.g. pneumonia, intestinal infection), which can trigger sepsis or ARDS. Serious disturbances in hemostasis (disseminated intravascular coagulopathy, consumption coagulopathy) can occur as complications.

The dysregulation the innate immune response and the blood coagulation system play key roles in sepsis and ARDS. In particular, the release of a plethora of cytokines (e.g. IL-27) and other inflammatory mediators (e.g. C5a) can be observed, which transduce their effects by complex mechanisms of intracellular signal transduction and orchestrate downstream effects on hemostasis. A special focus of our research is on the molecular interactions of the innate immune response with the coagulation system. A focus is on the immune-modulatory functions of linear polyphosphates, inflammatory mediators and intracellular signaling pathways in macrophages.

Our projects contribute to a better understanding of the molecular pathogenesis of sepsis and acute lung injury and will help to identify new strategies for effective treatment options.

Research Interests

• Molecular research of the molecular pathomechanisms of sepsis and acute lung injury (ARDS)
• Host-pathogen interactions and bacterial infections of organs with epithelial interfaces to the environment (intestines, lungs)
• Role of polyphosphates in immune metabolism, infection and hemostasis
• Cytokines (e.g. IL-27), complement factors (e.g. C5a) and signaling pathways
• Neutrophil extracellular traps 

Partners of Collaboration

• Prof. Dr. Wolfram Ruf (CTH)
• Jun.-Prof. Dr. Christoph Reinhardt (CTH)
• Prof. Dr. Tobias Bopp (Institut für Immunologie)
• Prof. Dr. Stefan Tenzer (Institut für Immunologie)

National Partners

• Prof. Dr. Heiko Mühl (Institut für Allgemeine Pharmakologie und Toxikologie, Johann Wolfgang Goethe-Universität Frankfurt)
• Prof. Dr. E. Schulze-Bahr (Institut für Genetik von Herzerkrankungen, Universitätsklinikum Münster)

International Partners

• Prof. Dr. Peter A. Ward (Department of Pathology, University of Michigan, Ann Arbor, USA)
• Prof. Dr. James H. Morrissey und Dr. Stephanie A. Smith (Department of Biochemistry, University of Illinois, Urbana, USA)
• Prof. Dr. Florian Douam (Department of Microbiology, Boston University, USA)

Research Funding

• DFG (German Research Foundation)

Biography - Markus Bosmann

Positions:
Since 2022 – Extraordinary Professorship, University Medical Center, Johannes Gutenberg-University, Mainz
Since 2018 – Faculty Member, Boston University School of Medicine
Since 2012 – Junior Group Leader 'Experimental Research', CTH, University Medical Center, Johannes Gutenberg-University, Mainz (since 2018 adjuct faculty)

Research Career:
2009 - 2012 – PostDoc, University of Michigan, Ann Arbor, USA

Academic and Medical Education:
2019 - Certified Immunologist, German Society of Immunology (DGfI)
2017 - Board Certification in Internal Medicine
2005 - MD Thesis, Frankfurt a.M.
1997 - 2004 – Medical Degree, Johann Wolfgang Goethe-University Frankfurt

ORCID Researcher ID:
0000-0003-2773-1033

Team - Juniorgroup Experimental Research

Alumni

• Dr. med. Norman Russkamp
• Dr. rer. nat. Dennis Riehl
• PD Dr. med. Robert Rümmler
• Dr. rer. nat. Julian Röwe
• Dr. med. Max Higer
• Dr. med. Georgios Stavrides
• Dr. med. Johannes Schoeche
• Dr. rer. nat. Marcel Strüve
• Dr. rer. nat. Frano Malinarich
• Dr. rer. nat. Markus Dudek
• Dr. rer. nat. Johannes Platten
• cand. med. Vanessa Tansi

Bosman Lab at Boston University, USA

Original Articles

• Roewe J, Walachowski S, Sharma A, Berthiaume KA, Reinhardt C, Bosmann M. Bacterial polyphosphates induce CXCL4 and synergize with complement anaphylatoxin C5a in lung injury. Front Immunol. 2022 Nov 3;13:980733. doi: 10.3389/fimmu.2022.980733
• Krenzlin V, Roewe J, Strueve M, Martínez-Negro M, Sharma A, Reinhardt C, Morsbach S, Bosmann M. Bacterial-Type Long-Chain Polyphosphates Bind Human Proteins in the Phosphatidylinositol Signaling Pathway. Thromb Haemost. 2022 Nov;122(11):1943-1947
• Chaudhary N, Jayaraman A, Reinhardt C, Campbell JD, Bosmann M. A single-cell lung atlas of complement genes identifies the mesothelium and epithelium as prominent sources of extrahepatic complement proteins. Mucosal Immunol. 2022 May;15(5):927-939.
• Kenney DJ, O'Connell AK, Turcinovic J, Montanaro P, Hekman RM, Tamura T, Berneshawi AR, Cafiero TR, Al Abdullatif S, Blum B, Goldstein SI, Heller BL, Gertje HP, Bullitt E, Trachtenberg AJ, Chavez E, Nono ET, Morrison C, Tseng AE, Sheikh A, Kurnick S, Grosz K, Bosmann M, Ericsson M, Huber BR, Saeed M, Balazs AB, Francis KP, Klose A, Paragas N, Campbell JD, Connor JH, Emili A, Crossland NA, Ploss A, Douam F. Humanized mice reveal a macrophage-enriched gene signature defining human lung tissue protection during SARS-CoV-2 infection. Cell Rep. 2022 Apr 19;39(3):110714.
• Sharma A, Noon JB, Kontodimas K, Garo LP, Platten J, Quinton LJ, Urban JF Jr, Reinhardt C, Bosmann M. IL-27 Enhances γδ T Cell-Mediated Innate Resistance to Primary Hookworm Infection in the Lungs. J Immunol. 2022 Apr 15;208(8):2008-2018.
• Carossino M, Kenney D, O'Connell AK, Montanaro P, Tseng AE, Gertje HP, Grosz KA, Ericsson M, Huber BR, Kurnick SA, Subramaniam S, Kirkland TA, Walker JR, Francis KP, Klose AD, Paragas N, Bosmann M, Saeed M, Balasuriya UBR, Douam F, Crossland NA. Fatal Neurodissemination and SARS-CoV-2 Tropism in K18-hACE2 Mice Is Only Partially Dependent on hACE2 Expression. Viruses. 2022 Mar 5;14(3):535
• Huang J, Hume AJ, Abo KM, Werder RB, Villacorta-Martin C, Alysandratos KD, Beermann ML, Simone-Roach C, Lindstrom-Vautrin J, Olejnik J, Suder EL, Bullitt E, Hinds A, Sharma A, Bosmann M, Wang R, Hawkins F, Burks EJ, Saeed M, Wilson AA, Mühlberger E, Kotton DN. SARS-CoV-2 Infection of Pluripotent Stem Cell-Derived Human Lung Alveolar Type 2 Cells Elicits a Rapid Epithelial-Intrinsic Inflammatory Response. Cell Stem Cell. 2020 Dec 3;27(6):962-973.e7.
• Roewe J, Stavrides G, Strueve M, Sharma A, Marini F, Mann A, Smith SA, Kaya Z, Strobl B, Mueller M, Reinhardt C, Morrissey JH, Bosmann M. Bacterial polyphosphates interfere with the innate host defense to infection. Nat Commun. 2020 Aug 12;11(1):4035.
• Sharma A, Steven S, Bosmann M. The pituitary gland prevents shock-associated death by controlling multiple inflammatory mediators. Biochem Biophys Res Commun 2019;509(1):188-193.
• Hansen M, Peltier J, Killy B, Amin B, Bodendorfer B, Hartlova A, Uebel S, Bosmann M, Hofmann J, Buttner C, Ekici AB, Kuttke M, Franzyk H, Foged C, Beer-Hammer S, Schabbauer G, Trost M, Lang R. Macrophage Phosphoproteome Analysis Reveals MINCLE-dependent and -independent Mycobacterial Cord Factor Signaling. Mol Cell Proteomics 2019;18(4):669-685.
• Gawish R, Bulat T, Biaggio M, Lassnig C, Bago-Horvath Z, Macho-Maschler S, Poelzl A, Simonovic N, Prchal-Murphy M, Rom R, Amenitsch L, Ferrarese L, Kornhoff J, Lederer T, Svinka J, Eferl R, Bosmann M, Kalinke U, Stoiber D, Sexl V, Krmpotic A, Jonjic S, Müller M, Strobl B. Myeloid Cells Restrict MCMV and Drive Stress-Induced Extramedullary Hematopoiesis through STAT1. Cell Rep 2019;26(9):2394-2406 e2395.
• Kröller-Schön S, Daiber A, Steven S, Oelze M, Frenis K, Kalinovic S, Heimann A, Schmidt FP, Pinto A, Kvandova M, Vujacic-Mirski K, Filippou K, Dudek M, Bosmann M, Klein M, Bopp T, Hahad O, Wild PS, Frauenknecht K, Methner A, Schmidt ER, Rapp S, Mollnau H, Münzel T. Crucial role for Nox2 and sleep deprivation in aircraft noise-induced vascular and cerebral oxidative stress, inflammation, and gene regulation. Eur Heart J 2018;39(38):3528-3539.
• Alflen A, Prüfer S, Ebner K, Reuter S, Aranda Lopez P, Scharrer I, Banno F, Stassen M, Schild H, Jurk K, Bosmann M, Beckert H, Radsak MP (2017) ADAMTS-13 regulates neutrophil recruitment in a mouse model of invasive pulmonary aspergillosis. Scientific reports 7: 7184
• Roewe J, Higer M, Riehl DR, Gericke A, Radsak MP, Bosmann M (2017) Neuroendocrine Modulation of IL-27 in Macrophages. Journal of immunology 199(7):2503-2514
• Schütz E, Bochenek ML, Riehl DR, Bosmann M, Münzel T, Konstantinides S, Schäfer K. Absence of transforming growth factor beta 1 in murine platelets reduces neointima formation without affecting arterial thrombosis. Thromb Haemost 2017;117(9):1782-1797.
• Kiouptsi K, Grill A, Mann A, Döhrmann M, Lillich M, Jäckel S, Malinarich F, Formes H, Manukyan D, Subramaniam S, Khandagale A, Karwot C, Thal SC, Bosmann M, Scharrer I, Jurk K, Reinhardt C (2017) Mice deficient in the anti-haemophilic coagulation factor VIII show increased von Willebrand factor plasma levels. PloS one 12: e0183590 
• Fattahi F, Kalbitz M, Malan EA, Abe E, Jajou L, Huber-Lang MS, Bosmann M, Russell MW, Zetoune FS, Ward PA (2017) Complement-induced activation of MAPKs and Akt during sepsis: role in cardiac dysfunction. FASEB journal 31(9):4129-4139
• Russkamp NF, Ruemmler R, Roewe J, Moore BB, Ward PA, Bosmann M. Experimental design of complement component 5a-induced acute lung injury (C5a-ALI): a role of CC-chemokine receptor type 5 during immune activation by anaphylatoxin. FASEB journal. pii: fj.15-271635, 2015.
• Kalbitz M, Grailer JJ, Fattahi F, Jajou L, Herron TJ, Campbell KF, Zetoune FS, Bosmann M, Sarma JV, Huber-Lang M, Gebhard F, Loaiza R, Valdivia HH, Jalife J, Russell MW, Ward PA. Role of extracellular histones in the cardiomyopathy of sepsis. FASEB journal. 29:2185-2193. 2015.
• Taddonio MA, Dolgachev V, Bosmann M, Ward PA, Su G, Wang SC, Hemmila MR. Influence of lipopolysaccharide-binding protein on pulmonary inflammation in gram-negative pneumonia. Shock. 43:612-619. 2015.
• Prüfer S, Weber M, Stein P, Bosmann M, Stassen M, Kreft A, Schild H, Radsak MP. Oxidative burst and neutrophil elastase contribute to clearance of Aspergillus fumigatus pneumonia in mice. Immunobiology. 219:87-96. 2014.
• Weber M, Rudolph B, Stein P, Yogev N, Bosmann M, Schild H, Radsak MP. 2014. Host-derived CD8(+) dendritic cells protect against acute graft-versus-host disease after experimental allogeneic bone marrow transplantation. Biology of blood and marrow transplantation. 20:1696-1704. 2014.
• Bosmann M, Russkamp NF, Strobl B, Roewe J, Balouzian L, Pache F, Radsak MP, van Rooijen N, Zetoune FS, Sarma JV, Nunez G, Muller M, Murray PJ, Ward PA. Interruption of macrophage-derived IL-27(p28) production by IL-10 during sepsis requires STAT3 but not SOCS3. Journal of immunology. 193:5668-5677, 2014.
• Bosmann M, Strobl B, Kichler N, Rigler D, Grailer JJ, Pache F, Murray PJ, Muller M, Ward PA. Tyrosine kinase 2 promotes sepsis-associated lethality by facilitating production of interleukin-27. J Leukoc Biol. doi:10.1189/jlb.3A1013-541R, 2014.
• Bosmann M, Grailer JJ, Ruemmler R, Russkamp NF, Zetoune FS, Sarma JV, Standiford TJ, Ward PA. Extracellular histones are essential effectors of C5aR- and C5L2-mediated tissue damage and inflammation in acute lung injury. FASEB Journal. 27(12):5010-21, 2013.
• Bosmann M, Meta F, Ruemmler R, Haggadone MD, Sarma JV, Zetoune FS, Ward PA. Regulation of IL-17 Family Members by Adrenal Hormones During Experimental Sepsis in Mice. American Journal of Pathology. 182(4):1124-30, 2013.
• Bosmann M, Zhu K, Grailer JJ, Matthay MA, Sarma JV, Zetoune FS, Ward PA. Anti-inflammatory Effects of ß2 Adrenergic Receptor Agonists in Experimental Acute Lung Injury. FASEB Journal. 26(5):2137-44, 2012.
• Bosmann M, Sarma JV, Atefi G, Zetoune FS, Ward PA. Evidence for anti-inflammatory effects of C5a on the innate IL-17A/IL-23 axis. FASEB Journal. 26(4):1640-51, 2012.
• Bosmann M, Haggadone MD, Hemmila MR, Zetoune FS, Sarma JV, Ward PA. Complement activation product C5a is a selective suppressor of TLR4-induced, but not TLR3-induced, production of IL-27(p28) from macrophages. Journal of Immunology. 188(10):5086-93, 2012.
• Bosmann M, Patel VR, Russkamp NF, Pache F, Zetoune FS, Sarma JV, Ward PA. MyD88-dependent production of IL-17F is modulated by the anaphylatoxin C5a: Role of the Akt signaling pathway. FASEB Journal. 25(12):4222-32, 2011.

Selected Reviews

• Subramaniam S, Ruf W, Bosmann M. Advocacy of targeting protease-activated receptors in severe coronavirus disease 2019. Br J Pharmacol. 2022 May;179(10):2086-2099.
• Sharma A, Kontodimas K, Bosmann M. The MAVS Immune Recognition Pathway in Viral Infection and Sepsis. Antioxid Redox Signal. 2021 Dec;35(16):1376-1392.
• Sharma A, Kontodimas K, Bosmann M. Nanomedicine: A Diagnostic and Therapeutic Approach to COVID-19. Front Med (Lausanne). 2021 Jun 4;8:648005.
• Bosmann M, Ward PA. Modulation of inflammation by interleukin-27. J Leukoc Biol. 2013 Dec;94(6):1159-65.
• Bosmann M, Ward PA. The inflammatory response in sepsis. Trends Immunol. 2013 Mar;34(3):129-36.

Editorials and Comments

• Bosmann M. Complement Activation during Critical Illness: Current Findings and an Outlook in the Era of COVID-19. Am J Respir Crit Care Med. 2020 Jul 15;202(2):163-165.
• Bosmann M. Complement control for COVID-19. Sci Immunol. 2021 May 25;6(59):eabj1014.