Schuller, Stephanie - University of East Anglia

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Schuller, Stephanie Dr 收藏完善纠错
University of East Anglia Department of Medicine
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个人简介

I always had a keen interest in the interactions between human pathogenic bacteria and their (unfortunate) hosts. After studying Biology at the universities of Bonn and Marburg in Germany, I finished my undergraduate studies with a one year diploma thesis on the gut pathogen Listeria monocytogenes in the laboratory of Prof Werner Goebel at the University of Würzburg. I stayed on for my PhD thesis where I investigated how Listeria modulates the macrophage immune response with particular interest on antigen presentation. After completion of my PhD I went to the UK to study the interactions of Mycobacterium bovis BCG with human macrophages and investigate the characteristics of the Mycobacterium-containing phagosome. This work was performed in the group of Prof Douglas Young and financed by a Marie Curie Fellowship. The final part of the project was completed at the Netherlands Cancer Institute in Amsterdam where I was hosted in the lab of Prof Jacques Neefjes. In 2001, I returned to London (and the human gut) and took up work with Prof Alan Phillips at the Royal Free Medical School at UCL. As it turned out, this was the start of a long-lasting relationship with enteropathogenic (EPEC) and enterohaemorrhagic E. coli (EHEC) and involved many productive collaborations with leading scientists in the area (Profs Gadi Frankel, Jim Kaper, Brendan Kenny, Jorge Giron). Particular areas of research included the application of in vitro organ culture of human intestinal biopsies to study EPEC- and EHEC-mediated signal transduction in intestinal epithelial cells and the subsequent innate immune response. A successful Wellcome Trust project grant also led to the development and application of a microaerobic in vitro human intestinal infection model which enabled me to study the influence of oxygen on bacterial virulence gene expression. In 2010, I moved to Norwich where I took up a lecturer position at the Norwich Medical School, UEA and became a Research Leader within in Gut Health & Food Safety Programme at the Institute of Food Research. In Nov 2011, I was awarded an MRC New Investigator Research Grant to study EHEC Shiga toxin translocation across the gut epithelium. Career History Lecturer, University of East Anglia, Oct 2010-present Research Associate, University College London, 2001–2010 Research Associate, Netherlands Cancer Institute, Amsterdam, 1999-2001 Research Associate, Imperial College London, 1997-1999 Academic Background PhD, University of Würzburg, Germany, 1997 Diplom, University of Marburg, Germany, 1994

研究领域

E. coli bacteria are usually known as harmless commensals in the human gut. However, several subsets of E. coli have acquired genetic elements which make them pathogenic to humans. Research in our laboratory is focused on pathogenesis of enteropathogenic (EPEC) and enterohaemorrhagic E. coli (EHEC) both of which are important foodborne pathogens. While EPEC is a major cause of infant diarrhoea in developing countries, EHEC is associated with bloody diarrhoea and severe kidney disease (Haemolytic Uraemic Syndrome/HUS) in children in the developed world. Both EPEC and EHEC share the ability to adhere to the human gut epithelium by forming characteristic attaching/effacing lesions. This is mediated by a type III secretion system which acts as a macromolecular syringe to inject bacterial effector proteins into the host cell. A multitude of effectors have been identified for EPEC and EHEC which interfere with a range of signal transduction pathways within the host cell and ultimately lead to the development of diarrhoea. EHEC also release Shiga toxins (Stx) which are associated with HUS and highly cytotoxic to renal microvasculature. HUS is the leading cause of acute kidney failure in children and currently there is no treatment for this potentially fatal disease. Research in our laboratory aims at understanding EPEC- and EHEC-mediated pathogenesis by using in vitro and ex vivo model systems that closely mimic the environment in the human gut. In collaboration with gastroenterologists at the Norfolk & Norwich University Hospital, we are using in vitro organ culture of human intestinal biopsies to investigate bacterial colonisation and gene expression, host innate immune response to infection and the use of probiotics as treatment strategies. In addition, we have established a vertical diffusion chamber (VDC) system which enables us to perform infections under microaerobic conditions similar to those in the human gut. By using the VDC system we are aiming to understand the influence of oxygen on bacterial virulence gene expression and pathogenesis, the role of Stx in intestinal pathology and the mechanism of Stx translocation across the gut barrier. Taken together, our research should lead to a better understanding of the early events during EPEC and EHEC pathogenesis and enable the design of more efficient treatment strategies.

近期论文

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Walsham, A., MacKenzie, D. A., Cook, V., Wemyss-Holden, S., Hews, C., Juge, N., Schuller, S.(2016)Lactobacillus reuteri Inhibition of Enteropathogenic Escherichia coli Adherence to Human Intestinal Epitheliumin Frontiers in Microbiology7. Full Text UEA Repository(Article) Lewis, S., Prior, A., Ellis, S., Cook, V., Chan, S., Gelson, W., Schuller, S.(2016)Flagellin induces β-defensin 2 in human colonic ex vivo infection with enterohemorrhagic Escherichia coliin Frontiers in Cellular and Infection Microbiology6. Full Text UEA Repository(Article) Lewis, S., Cook, V., Tighe, R., Schuller, S.(2015)Enterohemorrhagic Escherichia coli colonization of human colonic epithelium in vitro and ex vivoin Infection and Immunity83.pp. 942-949 Full Text UEA Repository(Article) Tran, S., Billoud, L., Lewis, S. B., Phillips, A. D., Schüller, S.(2014)Shiga toxin production and translocation during microaerobic human colonic infection with Shiga toxin-producing E. coli O157:H7 and O104:H4in Cellular Microbiology16.pp. 1255–1266 Full Text UEA Repository(Article) Fang, S., Schuller, S., Phillips, A. D.(2013)Human Intestinal In Vitro Organ Culture as a Model for Investigation of Bacteria-Host Interactionsin Journal of Experimental and Clinical Medicine5.pp. 43-50 Full Text UEA Repository(Article) Schuller, S.(2011)Shiga Toxin Interaction with Human Intestinal Epitheliumin Toxins3.pp. 626-639 Full Text UEA Repository(Article) Schuller, S., Phillips, A.(2010)Microaerobic conditions enhance type 111 secretion and adherence of enterohaemorrhagic Escherichia coli to polarized human intestinal epithelial cells.in Environmental Microbiology12.pp. 2426-2435 Full Text UEA Repository(Article) Crepin, V. F., Girard, F., Schuller, S., Phillips, A. D., Mousnier, A., Frankel, G.(2010)Dissecting the role of the Tir:Nck and Tir:IRTKS/IRSp53 signalling pathwaysin vivoin Molecular Microbiology75.pp. 308-323 Full Text UEA Repository(Article) Saldana, Z., Erdem, A. L., Schuller, S., Okeke, I. N., Lucas, M., Sivananthan, A., Phillips, A. D., Kaper, J. B., Puente, J. L., Giron, J. A.(2009)The Escherichia coli Common Pilus and the Bundle-Forming Pilus Act in Concert during the Formation of Localized Adherence by Enteropathogenic E. coliin Journal of Bacteriology191.pp. 3451-3461 Full Text UEA Repository(Article) Schuller, S., Lucas, M., Kaper, J. B., Girón, J. A., Phillips, A. D.(2009)The ex vivo response of human intestinal mucosa to enteropathogenic Escherichia coli infectionin Cellular Microbiology11.pp. 521-530 Full Text UEA Repository(Article) Bai, L., Schuller, S., Whale, A., Mousnier, A., Marches, O., Wang, L., Ooka, T., Heuschkel, R., Torrente, F., Kaper, J., Gomes, T., Xu, J., Phillips, A.(2008)Enteropathogenic Escherichia coli O125:H6 triggers attaching and effacing lesions on human intestinal biopsy specimens independently of Nck and TccP/TccP2.in Infection and Immunity76.pp. 361-368 Full Text UEA Repository(Article) Mousnier, A., Whale, A. D., Schuller, S., Leong, J. M., Phillips, A. D., Frankel, G.(2008)Cortactin Recruitment by Enterohemorrhagic Escherichia coli O157:H7 during Infection In Vitro and Ex Vivoin Infection and Immunity76.pp. 4669-4676 Full Text UEA Repository(Article) Zilbauer, M., Dorrell, N., Elmi, A., Lindley, K. J., Schuller, S., Jones, H. E., Klein, N. J., Núňez, G., Wren, B. W., Bajaj-Elliott, M.(2007)A major role for intestinal epithelial nucleotide oligomerization domain 1 (NOD1) in eliciting host bactericidal immune responses to Campylobacter jejuniin Cellular Microbiology9.pp. 2404-2416 Full Text UEA Repository(Article) Whale, A. D., Hernandes, R. T., Ooka, T., Beutin, L., Schuller, S., Garmendia, J., Crowther, L., Vieira, M. A. M., Ogura, Y., Krause, G., Phillips, A. D., Gomes, T. A. T., Hayashi, T., Frankel, G.(2007)TccP2-mediated subversion of actin dynamics by EPEC 2 - a distinct evolutionary lineage of enteropathogenic Escherichia coliin Microbiology153.pp. 1743-1755 Full Text UEA Repository(Article) Schuller, S., Chong, Y., Lewin, J., Kenny, B., Frankel, G., Phillips, A. D.(2007)Tir phosphorylation and Nck/N-WASP recruitment by enteropathogenic and enterohaemorrhagic Escherichia coli during ex vivo colonization of human intestinal mucosa is different to cell culture modelsin Cellular Microbiology9.pp. 1352-1364 Full Text UEA Repository(Article) Mundy, R., Schuller, S., Girard, F., Fairbrother, J. M., Phillips, A. D., Frankel, G.(2007)Functional studies of intimin in vivo and ex vivo: implications for host specificity and tissue tropismin Microbiology153.pp. 959-967 Full Text UEA Repository(Article) Schuller, S., Heuschkel, R., Torrente, F., Kaper, J. B., Phillips, A. D.(2007)Shiga toxin binding in normal and inflamed human intestinal mucosain Microbes and Infection9.pp. 35-39 Full Text UEA Repository(Article) Dean, P., Maresca, M., Schuller, S., Phillips, A., Kenny, B.(2006)Potent diarrheagenic mechanism mediated by the cooperative action of three enteropathogenic Escherichia coli-injected effector proteinsin Proceedings of the National Academy of Sciences103.pp. 1876-1881 Full Text UEA Repository(Article) Marches, O., Wiles, S., Dziva, F., La Ragione, R. M., Schuller, S., Best, A., Phillips, A. D., Hartland, E. L., Woodward, M. J., Stevens, M. P., Frankel, G.(2005)Characterization of Two Non-Locus of Enterocyte Effacement-Encoded Type III-Translocated Effectors, NleC and NleD, in Attaching and Effacing Pathogensin Infection and Immunity73.pp. 8411-8417 Full Text UEA Repository(Article) Garmendia, J., Phillips, A. D., Carlier, M., Chong, Y., Schuller, S., Marches, O., Dahan, S., Oswald, E., Shaw, R. K., Knutton, S., Frankel, G.(2004)TccP is an enterohaemorrhagic Escherichia coli O157:H7 type III effector protein that couples Tir to the actin-cytoskeletonin Cellular Microbiology6.pp. 1167-1183 Full Text UEA Repository(Article)

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