Markus Bosmann, MD
Leader Juniorgroup "Experimental Research"
Sepsis and acute lung injury (ALI, ARDS) are life-threatening diseases and frequently require treatment in critical care medicine. The annual incidence of sepsis and ALI is approximately 150,000 cases in Germany. Immunocompromised patients are under increased risk for the development of infections, which can progress to sepsis or/and ALI. Additional complications can arise from severe disturbances in the blood clotting system (e.g. disseminated intravascular coagulopathy) during sepsis and ALI.
Accumulating evidence suggests key roles of the coagulation system and innate immune responses during sepsis and ALI. The release of a plethora of inflammatory mediators (e.g. IL-27, C5a) is observed and accompanied by complex interactions of intracellular signaling cascades and down-stream effects on coagulation. The focus of our research projects is on the molecular interactions of blood coagulation and the innate immune responses. In detail, the roles of plasmatic and cellular components of coagulation are investigated. We study the immune-modulatory functions of platelets and role of coagulation factors in macrophages and type II alveolar epithelial cells. Additional projects are related to novel pathogen-associates molecular patterns (e.g. polyphosphates), signal transduction pathways (e.g. MAVS, MDA5, RIG-I) and neutrophil extracellular traps in the context of coagulopathies during sepsis and ALI.
Our studies will contribute to a better understanding of the molecular pathogenesis of sepsis and acute lung injury, thereby helping to identify new avenues for therapeutic interventions.
Molecular pathogenesis of sepsis and acute lung injury (ALI)
Interactions of acute inflammation and the coagulation system
Role of inflammatory mediators (e.g. IL-27) during innate immune responses
Cross-talk of the complement system and coagulation
- Host-pathogen interactions and pathogen-associated molecular patterns
- Neutrophil extracellular traps
Partners of Collaboration
Peter A. Ward, MD (Godfrey D. Stobbe Professor, Department of Pathology, University of Michigan, Ann Arbor, USA)
Professor James H. Morrissey, PhD (Professor of Biochemistry, Molecular and Cellular Biology, Department of Biochemistry) and Stephanie A. Smith, PhD (Assistant Professor, Department of Biochemistry), University of Illinois, Urbana, USA
Heiko Mühl, PhD (Professor of Pharmacology and Toxicology, Center of Pharmacology, Johann Wolfgang Goethe-University, Frankfurt a.M., Germany)
Peter J. Murray, PhD (Associate Member, St. Jude Faculty, Departments of Infectious Diseases and Immunology, St. Jude Children’s Research Hospital, Memphis, USA)
- Charles T. Esmon, PhD (Adjunct Professor, Departments of Biochemistry & Molecular Biology and Pathology, University Oklahoma Health Science Center, USA)
CTH/BMBF (Federal Ministry of Education and Research, Modul A, JG)
DFG (German Research Foundation, BO 3482/3-1)
- MAIFOR Program
Internal university research funding, Level I
EU Marie Curie Career Integration Grant (CIG)
EHA Clinical Research Fellowship
Team - Juniorgroup Experimental Research
Markus Bosmann, MD
Position: Juniorgroup leader, Physician, Assistant Professor for Molecular Medicine
Assistant Professor of Medicine, Boston University
- Norman Russkamp, Assistenzarzt, Zentrum für Hämatologie und Onkologie, UniversitätsSpital Zürich
- Dr. rer. nat. Dennis Riehl, Nationales Centrum für Tumorerkrankungen, Deutsches Krebsforschungszentrum, Heidelberg
- Dr. med. Robert Rümmler, Assistenzarzt, Klinik für Anästhesiologie
- Dr. rer. nat. Julian Röwe, DKFZ Heidelberg
- Ward PA, Fattahi F, Bosmann M. New Insights into Molecular Mechanisms of Immune Complex-Induced Injury in Lung. Frontiers in immunology 7:86. 2016.
- Bosmann M, Ward PA. Protein-based therapies for acute lung injury: targeting neutrophil extracellular traps. Expert Opin Ther Targets. 18:703-714, 2014.
- Bosmann M, Ward P. Modulation of inflammation by interleukin-27. Journal of Leukocyte Biology. 94(6):1159-65, 2013.
- Bosmann M, Ward PA. Role of C3, C5 and anaphylatoxin receptors in acute lung injury and in sepsis (Review). Adv Exp Med Biol. 946:147-59, 2012.
- Bosmann M., Ward P. A. The inflammatory response in sepsis. Trends Immunology. 1471-4906(12)00162-7, 2012.
- Ward P. A., Bosmann M. A historical perspective on sepsis. The American Journal of Pathology. 181(1):2-7, 2012.
- 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.