Markus Bosmann, M.D.

 

Assistant Professor of MedicineMarkus Bosmann_05-2012

mbosmann@bu.edu

Graduate School: Johann Wolfgang Goethe-University, Frankfurt a. M., Germany

Fellowship: University of Michigan, Ann Arbor, MI (Peter A. Ward, Department of Pathology)

Special Interests:

 Research:

  • Acute respiratory distress syndrome (ARDS)
  • Bacterial sepsis
  • Pneumonia
  • Lung fibrosis
  • Infection-associated inflammation
  • Host-pathogen interactions
  • Innate immunity
  • Macrophages, neutrophils, T cells, lung epithelial cells
  • Cytokines (e.g. IL-27/IL-27RA)
  • Complement system (e.g. C5a/C5aRs)
  • Signaling pathways (e.g. MAVS)
  • Gene editing (CRISPR/Cas9)

Sepsis and acute respiratory distress syndrome (ARDS) are life-threatening diseases and frequently require treatment in critical care medicine. Patients with bacterial pneumonia are under increased risks for the development of both ARDS and sepsis. There are estimated more than 600,000 annual cases of sepsis and ARDS in the United States. In the current absence of FDA-approved drugs, the mortality rates of ARDS and sepsis remain around 20-50%. Hence, these disorders represent important clinical problems with an urgent need for a better understanding of their pathogenesis.

Accumulating evidence suggests key roles of dysbalanced innate immune responses, inflammation and host-pathogen interactions during pneumonia, ARDS and sepsis. The presence of pathogen-associated molecular patterns (PAMPs) provokes the release of a plethora of inflammatory mediators (e.g. cytokines, complement anaphylatoxins) accompanied by complex interactions of intracellular signaling cascades. The focus of our experimental research projects is on the cellular and molecular mechanisms of these innate immune responses including macrophage functions, neutrophil extracellular trap (NETs) formation, cytokines/chemokines, complement, signaling pathways and novel bacterial PAMPs (e.g. polyphosphates). We employ transcriptome-wide screening approaches (RNA-Seq.) for identifying novel differentially expressed genes in experimental sepsis/ARDS and are experienced in generating new transgenic mouse models (e.g. Cre-lox, CRISPR/Cas9). In summary, our studies aim for a better understanding of the molecular pathogenesis of infection-associated inflammation during sepsis and ARDS, thereby helping to identify future avenues for therapeutic interventions.

Selected Publications:

  1. Bosmann M, Ward PA. Protein-based therapies for acute lung injury: Targeting neutrophil extracellular traps. Expert Opin Ther Targets. 2014 Jun;18(6):703-14.
  2. Bosmann M, Ward PA. The inflammatory response in sepsis. Trends Immunol. 2013 Mar;34(3):129-36.
  3. 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 J. 2012 Apr;26(4):1640-51.
  4. 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. J Immunol. 2012 May 15;188(10):5086-93.
  5. 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 J. 2013 Dec;27(12):5010-21.
  6. Bosmann M, Strobl B, Kichler N, Rigler D, Grailer JJ, Pache F, Murray PJ, Müller M, Ward PA. Tyrosine kinase 2 promotes sepsis-associated lethality by facilitating production of Interleukin-27. J Leukocyte Biol. 2014 Jul;96(1):123-31.
  7. Bosmann M, Russkamp NF, Strobl B, Roewe J, Balouzian L, Pache F, Radsak MP, van Rooijen N, Zetoune FS, Sarma JV, Núñez G, Müller M, Murray PJ, Ward PA. Interruption of macrophage-derived IL-27(p28) production by IL-10 during sepsis requires STAT3 but not SOCS3. J Immunol. 2014 Dec 1;193(11):5668-77.
  8. Russkamp NF, Rummler 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 J. 2015 Sep;29(9):3762-72.
  9. Roewe J, Higer M, Riehl DR, Gericke A, Radsak MP, Bosmann M. Neuroendocrine Modulation of IL-27 in Macrophages. J Immunol. 2017 Aug 23. [Epub ahead of print] 

     

    Selected Reprints:

    1. The inflammatory response in sepsis
    2. Extracellular histones & neutrophil extracellular traps
    3. Experimental ARDS

     

    Links:

      Bosmann Lab, University of Mainz, Germany