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AG Utermöhlen
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AG Utermöhlen

Group Leader: Prof. Dr. Olaf Utermöhlen
Phone: +49 221 478-32023 [Email protection active, please enable JavaScript.]

Selected publications

Co-workers:
Ulrike Karow (-32213 [Email protection active, please enable JavaScript.])

Research topic:
Innate and adaptive immunity in vivo

Aim of our research is to improve the understanding of the complex interactions between microbes and the host during infections. We use mainly two neurotropic viruses, the Lymphocytic Choriomeningitis Virus (LCMV) and the Zika Virus (ZIKV) as infectious pathogens. Depending e.g. on the virus strain, infection dose, or route of application, these viruses lead to rather different responses. During infections with these viruses, physiologic mechanisms of antiviral immunity as well as immunopathologic reactions inferring damage to the host may by characterized at any level from single cells, via organs to the whole organism.

With regard to the host side of immune responses, we are particularly interested in

a) molecular mechanisms involving reactive oxygen species (ROS) beyond the well-known direct antimicrobial effects of ROS

b) metabolism of sphingomyelins as important membrane lipids, which exert complex structural and functional roles

An improved understanding of physiologic and immunopathologic reactions may delineate novel antimicrobial and/or immunomodulatory approaches.

 

Selected publications:

Research focus: Antiviral immunity

Roman Sankowski, Jasmin Ahmari, Charlotte Mezö, Anna Lena Hrabě de Angelis, Vidmante Fuchs, Olaf Utermöhlen, Thorsten Buch, Thomas Blank, Mercedes Gomez de Agüero, Andrew J Macpherson, Daniel Erny. Host  microbiota regulate selective myeloid subsets in the central nervous system during homeostasis and disease.  EMBO J. 2021 Dec 1;40(23):e108605. doi: 10.15252/embj.2021108605. Epub 2021 Oct 7.PMID: 34622466 

Elke Gabriel, Anand Ramani, Ulrike Karow, Marco Gottardo, Karthick Natarajan, Li Ming Gooi, Gladiola Goranci-Buzhala, Oleg Krut, Franziska Peters, Milos Nikolic, Suvi Kuivanen, Essi Korhonen, Teemu Smura, Olli Vapalahti, Argyris Papantonis, Jonas Schmidt-Chanasit, Maria Riparbelli, Giuliano Callaini, Martin Krönke, *Olaf Utermöhlen, *Jay Gopalakrishnan (*shared senior authorship) Recent Zika Virus Isolates Induce Premature Differentiation of Neural Progenitors in Human Brain Organoids. Cell Stem Cell. 20(3): 397-406. 2017

Kristin Jakobshagen, Beate Ward, Nikola Baschuk, Sebastian Huss, Anna Brunn, Monika Malecki, Michael Fiolka, Gunther Rappl, Diana Corogeanu, Ulrike Karow, Petra Schiller, Hinrich Abken, Lukas C. Heukamp, Martina Deckert, Martin Krönke, Olaf Utermöhlen. Endogenous IL-10 alleviates the systemic antiviral cellular immune response and T cell-mediated immunopathology in select organs of acutely LCMV-infected mice. Am J Pathol, 185: 3025-38. 2015

Daniel Erny D, Anna Lena Hrabě de Angelis, Diego Jaitin, Peter Wieghofer, Ori Staszewski , Eyal David, Hadas Keren-Shaul, Tanel Mahlakoiv, Kristin Jakobshagen, Thorsten Buch, Vera Schwierzeck, Olaf Utermöhlen, Eunyoung Chun, Wendy S. Garrett, Kathy D. McCoy, Andreas Diefenbach, Peter Staeheli, Bärbel Stecher, Odo Amit, Marco Prinz. Host microbiota constantly control maturation and function of microglia in the CNS. Nat Neurosci. 18: 965-77. 2015

Lars Ketscher, Ronny Hannß, David Morales, Anja Basters, Susana Guerra, Tobias Goldmann, Annika Hausmann, Marco Prinz, Ronald Naumann, Andrew Pekosz, Olaf Utermöhlen, Deborah J. Lenschow, Klaus-Peter Knobeloch. Selective inactivation of USP18 isopeptidase activity in vivo enhances ISG15 conjugation and viral resistance. Proc Natl Acad Sci U S A. 112:1577-82. 2015

Jasmin Herz, Julian Pardo, Hamid Kashkar, Michael Schramm, Erik Bos, Katja  Wiegmann, Reinhard Wallich, Peter J. Peters, Elmon Schmelzer, Martin Krönke, Markus M. Simon, Olaf Utermöhlen. Acid sphingomyelinase is a critical regulator of cytotoxic granule secretion by primary T lymphocytes. Nature Immunology 10:761-768. 2009.

 

Research focus: Reactive oxygen species (ROS) in antimicrobial immunity

Carolyn Morris, Aida Habibovic, Christopher Dustin, Caspar Schiffers, Miao-Chong Lin, Yvonne M.W. Janssen-Heininger, Matthew E. Poynter, Olaf Utermöhlen, Martin Kröncke, Albert van der Vliet. Macrophage-intrinsic DUOX1 contributes to type 2 inflammation and mucus metaplasia during chronic allergic airway disease. Mucosal Immunol. 2022 May;15(5):977-989. doi: 10.1038/s41385-022-00530-x. Epub 2022 Jun 2.PMID: 35654836

Bettina Tosetti, Beate Ward, Daniela Grumme,  Michael Schramm,  Olaf Utermöhlen, Lucas C. Heukamp,  Martin Krönke, Oleg Krut. NOX2 deficiency permits sustained survival of S. aureus in macrophages contributes to severity of infection. Frontiers in Immunology 2021 Mar 22;12:633629. doi: 10.3389/fimmu.2021.633629. eCollection 2021.PMID: 33868252

Utermöhlen O, Jakobshagen K, Blissenbach B, Wiegmann K, Merz T, Hefti JP, Krönke M. Emergence of AnnexinVpos CD31neg CD42blow/neg extracellular vesicles in plasma of humans at extreme altitude. PLoS One. 2019 Aug 1;14(8):e0220133. doi: 10.1371/journal.pone.0220133. eCollection 2019.

Marc Herb, Alexander Gluschko, Katja Wiegmann, Alina Farid, Anne Wolf, Olaf Utermöhlen, Oleg Krut, Martin Krönke, Michael Schramm. Mitochondrial reactive oxygen species enable proinflammatory signaling through disulfide linkage of NEMO. Sci Signal. 2019 Feb 12;12(568). pii: eaar5926. doi: 10.1126/scisignal.aar5926.

Michael Schramm, Katja Wiegmann, Sandra Schramm, Olaf Utermöhlen, Martin Krönke.  Riboflavin (vitamin B2) deficiency impairs phagocytic ROS production and defense against Listeria monocytogenes. Eur. J. Immunol., 44:728-41. 2014

 

Research focus: Sphingomyelinases in immunity and beyond

Khadija El-Hindi, Sebastian Brachtendorf, Jennifer Christina Hartel, Stephanie Örtel, Kerstin Birod, Nadine Merz, Sandra Trautmann, Dominique Thomas, Andreas Weigert, Tim J. Schäufele, Klaus Scholich, Susanne Schiffmann, Thomas Ulshöfer, Olaf Utermöhlen, Sabine Grösch. T-cell specific CerS4 depletion prolongs inflammation and en-hances tumor burden in the AOM/DSS induced CAC model. Int J Mol Sci. 2022 Feb 7;23(3):1866. doi: 10.3390/ijms23031866.PMID: 35163788

Khadija El-Hindi, Sebastian Brachtendorf, Jennifer Christina Hartel, Stephanie Oertel, Kerstin Birod, Sandra Trautmann, Dominique Thomas, Thomas Ulshöfer, Andreas Weigert, Olaf Utermöhlen, Martin Krönke, Sabine Grösch. Ceramide Synthase 5 deficiency aggravates dextran sodium sulfate-induced colitis and colon carcinogenesis and impairs T-cell activation. Cancers (Basel). 2020 Jul 1;12(7):1753. doi: 10.3390/cancers12071753.

Franziska Peters, Frederik Tellkamp, Susanne Brodesser, Emmi Wachsmuth, Bettina Tosetti, Ulrike Karow, Wilhelm Bloch, Olaf Utermöhlen, Martin Krönke, Carien M. Niessen. Murine Epidermal Ceramide Synthase 4 is a Key Regulator of Skin Barrier Homeostasis. J Invest Dermatol. 2020 Oct;140(10):1927-1937.e5. doi: 10.1016/j.jid.2020.02.006. Epub 2020 Feb 22.

Bettina Tosetti, Susanne Brodesser, Anna Brunn, Martina Deckert, M. Blüher, Wolfram Doehner, Stefan D. Anker, D. Wenzel, Bernd Fleischmann, Carola Pongratz, Franziksa Peters, Olaf Utermöhlen, Martin Krönke. A tissue-specific screen of ceramide expression in aged mice identifies Ceramide Synthase-1 and -5 as potential regulators of fiber size and strength in skeletal muscle. Aging Cell. 2020 Jan;19(1):e13049. doi: 10.1111/acel.13049.

Katharina Dannhausen, Marcus Karlstetter, Albert Caramoy, Cornelia Volz, Herbert Jaegle, Gerhard Liebisch, Olaf Utermöhlen, Thomas Langmann. Acid sphingomyelinase (aSMase) deficiency leads to abnormal microglia behavior and disturbed retinal function. Biochem Biophys Res Com, 2015 Aug 21;464(2):434-40. doi: 10.1016/j.bbrc.2015.06.133

 

Further cooperative projects

Arina Riabinska, Daria Lehrmann, Ron Daniel Jachimowicz, Gero Knittel, Christian Fritz, Anna Schmitt, Aenne Geyer, Carola Heneweer, Maike Wittersheim, Lukas P. Frenzel, Alessandro Torgovnick, Janica Lea Wiederstein, Claudia Maria Wunderlich, Monika Ortmann, Arlette Paillard, Wilhelm Wößmann, Arndt Borkhardt, Stefan Burdach, Martin-Leo Hansmann, Andreas Rosenwald, Sven Perner, Gita Mall, Wolfram Klapper, Andrea Merseburg, Marcus Krüger, Holger Grüll, Thorsten Persigehl, Frank Thomas Wunderlich, Martin Peifer, Olaf Utermöhlen, Reinhard Büttner, Filippo Beleggia, Hans Christian Reinhardt. ATM activity in T-cells is critical for immune surveillance of lymphoma in vivo. Leukemia. 2020 Mar;34(3):771-786. doi: 10.1038/s41375-019-0618-2.

Monica Sánchez-Ruiz, NKPolakos, Tobias Blau, Olaf Utermöhlen, Anna Brunn, Manuel Montesinos-Rongen, Thomas Hünig, Martina Deckert. TLR signals license CD8 T cells to destroy oligodendrocytes expressing an antigen shared with a Listeria pathogen. Eur J Immunol. 2019 Jan 22. doi: 10.1002/eji.201847834. [Epub ahead of print] PMID: 30666625

Kristine von Bargen, Mirella Scraba, Ina Krämer, Maren Ketterer, Christian Nehls, Sina Krokowski, Urska Repnik, Michaela Wittlich, Anna Maaser, Pia Zapka, Madeleine Bunge, Martin Schlesinger, Gitta Huth, Annette Klees, Philipp Hansen, Andreas Jeschke, Gerd Bendas, Olaf Utermöhlen, Gareth Griffiths, Thomas Gutsmann, Jens Wohlmann, Albert Haas. VapA from Rhodococcus equi is an inter-compartment pH-neutralising virulence factor. Cellular Microbiology 2019 Jan;21(1):e12958. doi: 10.1111/cmi.12958. Epub 2018 Nov 9. PMID: 30251327

Alexander Gluschko, Marc Herb, Katja Wiegmann, Oleg Krut, Wolfram Friedrich Neiss, Olaf Utermöhlen, Martin Krönke, Michael Schramm. The β2 integrin Mac-1 induces protective LC3-associated phagocytosis of Listeria monocytogenes Cell Host and Microbe, 23(3):324-337. 2018

Kerstin Wennhold, Martin Thelen, Hans Anton Schlößer, Natalie Haustein, Sabrina Reuter, Maria Garcia-Marquez, Axel Lechner, Sebastian Kobold, Felicitas Rataj, Olaf Utermöhlen, Geothy Chakupurakal, Sebastian Theurich, Michael Hallek, Hinrich Abken, Alexander Shimabukuro-Vornhagen, Michael von Bergwelt-Baildon. Using antigen-specific B cells to combine antibody and T cell based cancer immunotherapy. Cancer Immunology Research, 5(9):730-743. 2017

Marianna Hösel, Anke Huber, Susanne Bohlen, Julie Lucifora, Giuseppe Ronzitti, Francesco Puzzo, Florence Boisgerault, Ulrich T. Hacker, Nora Klöting, Matthias Blüher, Alexander Gluschko, Michael Schramm, Olaf Utermöhlen, Wilhelm Bloch, Federico Mingozzi, Oleg Krut, Hildegard Büning. Autophagy Determines Efficiency of Liver-directed Gene Therapy with Adeno-associated Viral Vectors. Hepatology, 2017 Mar 20. doi: 10.1002/hep.29176. [Epub ahead of print] PMID: 28318036

Anna Brunn, Mirna Mihelcic, Mariana Carstov, Lisa Feind, Eva C. Wieser, Julia Schmidt, Olaf Utermöhlen, Martina Deckert. Toll-Like Receptor 2, Toll-like Receptor 4, Myeloid Differentiation Response Gene 88, and Toll-IL-1 Receptor Domain-Containing Adaptor-inducen Interferon- (TRIF) selectively regulate susceptibility of P0106-125-induced murine experimental autoimmune neuritis. Am J Pathol, 187:42-54. 2017

Maria A. Ermolaeva, Alexandra Segred, Alexander Dakhovnik, Hui-Ling Ou, Jennifer I. Schneider, Olaf Utermöhlen, Thorsten Hoppe, Björn Schumacher. DNA damage in germ cells induces innate immune response triggering systemic stress resistance through enhanced proteostasis. Nature, 501: 416-20. 2013

 

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