Honors & Awards


  • Seed Grant, Stanford Center for Innovation in Global Health (2018)
  • Marie Curie Actions Initial Training Network Fellowship, European Initiative for Basic Research in Microbiology and Infectious Diseases (2011-2014)

Boards, Advisory Committees, Professional Organizations


  • Event Organizer, Stanford Microbiome Summit 2017 (2017 - 2017)
  • Member, Marie Curie Alumni Association (2016 - Present)
  • Trainee Member, Society for Mucosal Immunology (2016 - Present)
  • Event Coordinator, Pint of Science US (San Francisco) (2016 - 2016)
  • Vice President, StaPa (Young Researchers Association at the Institut Pasteur Paris) (2013 - 2014)

Professional Education


  • Doctor of Philosophy, Université Pierre et Marie Curie - Paris VI, Comlexité du Vivant (2014)
  • Master of Science, Charité Berlin, Molecular Medicine (2010)
  • Bachelor of Science, University of Konstanz, Life Sciences (2008)

Stanford Advisors


Current Research and Scholarly Interests


Studying the host-microbiome relationship in very early-onset inflammatory bowel disease via microbial DNA sequencing and analysis. Evaluating expression of antimicrobial peptides and other immune mediators in human stool via mass spectrometry in collaboration with the Elisa lab on campus. Another project focuses on the gut and skin microbiome in children with severe acute malnutrition in Bangladesh (in collaboration with Gary Darmstadt).

Lab Affiliations


All Publications


  • Clostridium difficile, Aging, and the Gut: Can Microbiome Rejuvenation Keep Us Young and Healthy? The Journal of infectious diseases Fischer, N., Relman, D. A. 2018; 217 (2): 174–76

    View details for PubMedID 28968708

  • Histone deacetylase inhibition enhances antimicrobial peptide but not inflammatory cytokine expression upon bacterial challenge PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Fischer, N., Sechet, E., Friedman, R., Amiot, A., Sobhani, I., Nigro, G., Sansonetti, P. J., Sperandio, B. 2016; 113 (21): E2993-E3001

    Abstract

    Antimicrobial peptides (AMP) are defense effectors of the innate immunity playing a crucial role in the intestinal homeostasis with commensals and protection against pathogens. Herein we aimed to investigate AMP gene regulation by deciphering specific characteristics allowing their enhanced expression among innate immune genes, particularly those encoding proinflammatory mediators. Our emphasis was on epigenetic regulation of the gene encoding the AMP β-defensin 2 (HBD2), taken as a model of possibly specific induction, upon challenge with a commensal bacterium, compared with the proinflammatory cytokine IL-8. Using an in vitro model of colonic epithelial cells challenged with Escherichia coli K12, we showed that inhibition of histone deacetylases (HDAC) by trichostatin A dramatically enhanced induction of HBD2 expression, without affecting expression of IL-8. This mechanism was supported by an increased phosphorylation of histone H3 on serine S10, preferentially at the HBD2 promoter. This process occurred through activation of the IκB kinase complex, which also led to activation of NF-κB. Moreover, we demonstrated that NF-κB was modified by acetylation upon HDAC inhibition, partly by the histone acetyltransferase p300, and that both NF-κB and p300 supported enhanced induction of HBD2 expression. Furthermore, we identified additional genes belonging to antimicrobial defense and epithelial restitution pathways that showed a similar pattern of epigenetic control. Finally, we confirmed our finding in human colonic primary cells using an ex vivo organoid model. This work opens the way to use epigenetic pharmacology to achieve induction of epithelial antimicrobial defenses, while limiting the deleterious risk of an inflammatory response.

    View details for DOI 10.1073/pnas.1605997113

    View details for Web of Science ID 000376779900017

    View details for PubMedID 27162363

  • Mucosal physical and chemical innate barriers: Lessons from microbial evasion strategies SEMINARS IN IMMUNOLOGY Sperandio, B., Fischer, N., Sansonetti, P. J. 2015; 27 (2): 111-118

    Abstract

    The innate immune system has evolved since millions of years under a selective pressure. Among the different host mechanisms selected and conserved as a first line of defense, the gastrointestinal mucus layer constitutes an efficient physical and chemical barrier against invading microbes. Mucin glycoproteins and antimicrobial peptides are the major components of the mucus barrier, and evidences prove that they form an effective protection against most microbes. However, successful pathogens have evolved evasion strategies to circumvent this defense barrier. Here, we discuss the interactions between pathogens, mucins, and antimicrobial peptides, and the mechanisms that pathogens have developed to evade the innate defense systems of the intestinal mucosal barrier.

    View details for DOI 10.1016/j.smim.2015.03.011

    View details for Web of Science ID 000355893500005

    View details for PubMedID 25936225

  • Virulent Shigella flexneri Affects Secretion, Expression, and Glycosylation of Gel-Forming Mucins in Mucus-Producing Cells INFECTION AND IMMUNITY Sperandio, B., Fischer, N., Chevalier-Curt, M. J., Rossez, Y., Roux, P., Masselot, C. R., Sansonetti, P. J. 2013; 81 (10): 3632-3643
  • Deciphering the intracellular fate of Propionibacterium acnes in macrophages. BioMed research international Fischer, N., Mak, T. N., Shinohara, D. B., Sfanos, K. S., Meyer, T. F., Brüggemann, H. 2013; 2013: 603046-?

    Abstract

    Propionibacterium acnes is a Gram-positive bacterium that colonizes various niches of the human body, particularly the sebaceous follicles of the skin. Over the last years a role of this common skin bacterium as an opportunistic pathogen has been explored. Persistence of P. acnes in host tissue has been associated with chronic inflammation and disease development, for example, in prostate pathologies. This study investigated the intracellular fate of P. acnes in macrophages after phagocytosis. In a mouse model of P. acnes-induced chronic prostatic inflammation, the bacterium could be detected in prostate-infiltrating macrophages at 2 weeks postinfection. Further studies performed in the human macrophage cell line THP-1 revealed intracellular survival and persistence of P. acnes but no intracellular replication or escape from the host cell. Confocal analyses of phagosome acidification and maturation were performed. Acidification of P. acnes-containing phagosomes was observed at 6 h postinfection but then lost again, indicative of cytosolic escape of P. acnes or intraphagosomal pH neutralization. No colocalization with the lysosomal markers LAMP1 and cathepsin D was observed, implying that the P. acnes-containing phagosome does not fuse with lysosomes. Our findings give first insights into the intracellular fate of P. acnes; its persistency is likely to be important for the development of P. acnes-associated inflammatory diseases.

    View details for DOI 10.1155/2013/603046

    View details for PubMedID 23862148

  • Propionibacterium acnes host cell tropism contributes to vimentin-mediated invasion and induction of inflammation CELLULAR MICROBIOLOGY Mak, T. N., Fischer, N., Laube, B., Brinkmann, V., Metruccio, M. M., Sfanos, K. S., Mollenkopf, H., Meyer, T. F., Brueggemann, H. 2012; 14 (11): 1720-1733

    Abstract

    The contribution of the human microbiota to health and disease is poorly understood. Propionibacterium acnes is a prominent member of the skin microbiota, but is also associated with acne vulgaris. This bacterium has gained recent attention as a potential opportunistic pathogen at non-skin infection sites due to its association with chronic pathologies and its isolation from diseased prostates. We performed comparative global-transcriptional analyses for P. acnes infection of keratinocytes and prostate cells. P. acnes induced an acute, transient transcriptional inflammatory response in keratinocytes, whereas this response was delayed and sustained in prostate cells. We found that P. acnes invaded prostate epithelial cells, but not keratinocytes, and was detectable intracellularly 7 days post infection. Further characterization of the host cell response to infection revealed that vimentin was a key determinant for P. acnes invasion in prostate cells. siRNA-mediated knock-down of vimentin in prostate cellsattenuated bacterial invasion and the inflammatory response to infection. We conclude that host cell tropism, which may depend on the host protein vimentin, is relevant for P. acnes invasion and in part determines its sustained inflammatory capacity and persistence of infection.

    View details for DOI 10.1111/j.1462-5822.2012.01833.x

    View details for Web of Science ID 000310072400006

    View details for PubMedID 22759266

  • Growth temperature-dependent expression of structural variants of Listeria monocytogenes lipoteichoic acid IMMUNOBIOLOGY Dehus, O., Pfitzenmaier, M., Stuebs, G., Fischer, N., Schwaeble, W., Morath, S., Hartung, T., Geyer, A., Hermann, C. 2011; 216 (1-2): 24-31

    Abstract

    Investigating the expression of lipoteichoic acid (LTA) from Listeria monocytogenes, we found two distinct structural variants of LTA (LTA1 and LTA2) using NMR and MS technology. While both LTA consisted of a poly-glycerophosphate backbone (differing in length) bound via a disaccharide to a diacyl-glycerol moiety, one LTA type (LTA2) possessed a second diacyl-glycerol moiety linked to the disaccharide via a phosphodiester. As examined in vitro, LTA2 in contrast to LTA1 failed to activate the L-ficolin dependent pathway of complement. Most interestingly, growth temperature had a strong influence on the expression levels of LTA1 and LTA2 in the cell wall: while the amount of LTA1 was comparable, the expression of LTA2 was low when Listeria had grown at room temperature (ratio of LTA1 to LTA2 was 1:0.06), but increased when Listeria had been cultivated at 37°C (ratio of LTA1 to LTA2 was 1:0.68). The observed shift in LTA expression, probably accompanying the switch from the saprophytic to the virulent entity, indicates an important adaptation to the different structural requirements inside the host cells.

    View details for DOI 10.1016/j.imbio.2010.03.008

    View details for Web of Science ID 000286403300003

    View details for PubMedID 20413180

  • Constitutive, agonist-accelerated, recycling and lysosomal degradation of GABA(B) receptors in cortical neurons MOLECULAR AND CELLULAR NEUROSCIENCE Grampp, T., Notz, V., Broll, I., Fischer, N., Benke, D. 2008; 39 (4): 628-637

    Abstract

    Endocytosis is considered as an important mechanism for regulating cell surface numbers and thereby signaling strength of G protein-coupled receptors. Currently, little is known about the endocytotic pathways of GABA(B) receptors in neurons. Here we report that GABA(B) receptors are constitutively internalized presumably via clathrin-dependent endocytosis in cultured cortical neurons. Colocalization of GABA(B) receptors with endosomal marker proteins indicated sorting of GABA(B) receptors from early endosomes to recycling endosomes and to lysosomes. Cell surface biotinylation experiments revealed fast constitutive recycling of GABA(B) receptors as the predominant pathway that was accelerated by the GABA(B) receptor agonist baclofen. Finally, degradation of GABA(B) receptors in lysosomes was demonstrated by their intracellular accumulation upon inhibition of lysosomal proteases and by blocking recycling which resulted in the redirection of receptors to lysosomes for degradation. These data imply rapid constitutive - agonist-accelerated - recycling of GABA(B) receptors presumably via clathrin-coated pits and their final targeting to lysosomes for degradation.

    View details for DOI 10.1016/j.mcn.2008.09.004

    View details for Web of Science ID 000261541600013

    View details for PubMedID 18948198