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Tor Savidge Lab



Recent Publications


Li S, Shi L, Yang Z, Zhang Y, Perez-Cordon G, Huang T, Ramsey J, Oezguen N, Savidge TC, Feng H. Critical roles of Clostridium difficile toxin B enzymatic activities in pathogenesis. Infect Immun. 2015 Feb;83(2):502-13. doi: 10.1128/IAI.02316-14. Epub 2014 Nov 17. PubMed PMID: 25404023; PubMed Central PMCID: PMC4294253.

Joffré E, von Mentzer A, Abd El Ghany M, Oezguen N, Savidge T, Dougan G, Svennerholm AM, Sjöling Å. Allele variants of enterotoxigenic Escherichia coli heat-labile toxin are globally transmitted and associated with colonization factors. J Bacteriol. 2015 Jan;197(2):392-403. doi: 10.1128/JB.02050-14. Epub 2014 Nov 17. PubMed PMID: 25404692; PubMed Central PMCID: PMC4272596.

MacEachern SJ, Patel BA, Keenan CM, Dicay M, Chapman K, McCafferty DM, Savidge TC, Beck PL, MacNaughton WK, Sharkey KA. Inhibiting Inducible Nitric Oxide Synthase in Enteric Glia Restores Electrogenic Ion Transport in Mice With Colitis. Gastroenterology. 2015 Aug;149(2):445-55.e3. doi: 10.1053/j.gastro.2015.04.007. Epub 2015 Apr 9. PubMed PMID: 25865048; PubMed Central PMCID: PMC4516675.

Savidge TC. Epigenetic Regulation of Enteric Neurotransmission by Gut Bacteria. Front Cell Neurosci. 2016 Jan 8;9:503. doi: 10.3389/fncel.2015.00503. eCollection 2015. Review. PubMed PMID: 26778967; PubMed Central PMCID: PMC4705220.

Chen D, Oezguen N, Urvil P, Ferguson C, Dann SM, Savidge TC. Regulation of protein-ligand binding affinity by hydrogen bond pairing. Sci Adv. 2016 Mar 25;2(3):e1501240. doi: 10.1126/sciadv.1501240. eCollection 2016 Mar. PubMed PMID: 27051863; PubMed Central PMCID: PMC4820369.

Yu H, Chen K, Wu J, Yang Z, Shi L, Barlow LL, Aronoff DM, Garey KW, Savidge TC, von Rosenvinge EC, Kelly CP, Feng H. Identification of toxemia in patients with Clostridium difficile infection. PLoS One. 2015 Apr 17;10(4):e0124235. doi: 10.1371/journal.pone.0124235. eCollection 2015. PubMed PMID: 25885671; PubMed Central PMCID: PMC4401762.

Chen D, Savidge T. BIOPHYSICS. Comment on "Extreme electric fields power catalysis in the active site of ketosteroid isomerase". Science. 2015 Aug 28;349(6251):936. doi: 10.1126/science.aab0095. Epub 2015 Aug 27. PubMed PMID: 26315427; PubMed Central PMCID: PMC4797066. 8: Savidge TC. Importance of NO and its related compounds in enteric nervous system regulation of gut homeostasis and disease susceptibility. Curr Opin Pharmacol. 2014 Dec;19:54-60. doi: 10.1016/j.coph.2014.07.009. Epub 2014 Aug 7. Review. PubMed PMID: 25108170; PubMed Central PMCID: PMC4254210.

Couturier J, Hutchison AT, Medina MA, Gingaras C, Urvil P, Yu X, Nguyen C, Mahale P, Lin L, Kozinetz CA, Schmitz JE, Kimata JT, Savidge TC, Lewis DE (2014).HIV replication in conjunction with granzyme B production by CCR5+ memory CD4 T cells: Implications for bystander cell and tissue pathologies. Virology;462-463:175-88. doi: 10.1016/j.virol.2014.06.008.

Sharkey KA, Savidge TC (2014). Reprint of: Role of enteric neurotransmission in host defense and protection of the gastrointestinal tract. Auton Neurosci;182:70-82. doi: 10.1016/j.autneu.2014.03.004.

Chumpitazi BP, Hollister EB, Oezguen N, Tsai CM, McMeans AR, Luna RA, Savidge TC, Versalovic J, Shulman RJ (2014). Gut microbiota influences low fermentable substrate diet efficacy in children with irritable bowel syndrome. Gut Microbes;5(2):165-75. doi: 10.4161/gmic.27923.

Mayer EA, Savidge T, Shulman RJ (2014). Brain-gut microbiome interactions and functional bowel disorders. Gastroenterology;146(6):1500-12. doi:10.1053/j.gastro.2014.02.037.

Sharkey KA, Savidge TC (2014). Role of enteric neurotransmission in host defense and protection of the gastrointestinal tract. Auton Neurosci;181:94-106.doi: 10.1016/j.autneu.2013.12.006

Peniche AG, Savidge TC, Dann SM (2013). Recent insights into Clostridium difficile pathogenesis. Curr Opin Infect Dis;26(5):447-53. doi:10.1097/01.qco.0000433318.82618.c6.

Juneau C, Mendias EN, Wagal N, Loeffelholz M, Savidge T, Croisant S, Dann S (2013). Community-Acquired Clostridium Difficile Infection: Awareness and Clinical Implications. J Nurse Pract;9(1):1-6.

Zhang, Y., L. Shi, S. Li, Z. Yang, C. Standley, R. ZhuGe, T. Savidge, X. Wang and H. Feng (2013). "A segment of 97 amino acids within the translocation domain of Clostridium difficile toxin B is essential for toxicity." PloS one 8(3): e58634.

Wang, H., X. Sun, Y. Zhang, S. Li, K. Chen, L. Shi, W. Nie, R. Kumar, S. Tzipori, J. Wang, T. Savidge and H. Feng (2012). "A chimeric toxin vaccine protects against primary and recurrent Clostridium difficile infection." Infection and immunity 80(8): 2678-2688.

Savidge, T. O. and F. Stein (2012). "Prevention, treatment, and recovery supports for those with substance use problems: opportunities for enhanced access and quality of care." North Carolina medical journal 73(3): 209-211.

Oezguen, N., T. D. Power, P. Urvil, H. Feng, C. Pothoulakis, J. S. Stamler, W. Braun and T. C. Savidge (2012). "Clostridial toxins: sensing a target in a hostile gut environment." Gut microbes 3(1): 35-41.

Medina, M. A., J. Couturier, M. L. Feske, A. E. Mahne, M. Turner, X. Yu, C. A. Kozinetz, A. F. Orozco, A. T. Hutchison, T. C. Savidge, J. R. Rodgers and D. E. Lewis (2012). "Granzyme B- and Fas ligand-mediated cytotoxic function induced by mitogenic CD28 stimulation of human memory CD4+ T cells." Journal of leukocyte biology 91(5): 759-771.

Wiktorowicz, J. E., S. Stafford, H. Rea, P. Urvil, K. Soman, A. Kurosky, J. R. Perez-Polo and T. C. Savidge (2011). "Quantification of cysteinyl S-nitrosylation by fluorescence in unbiased proteomic studies." Biochemistry 50(25): 5601-5614.

Van Landeghem, L., J. Chevalier, M. M. Mahe, T. Wedel, P. Urvil, P. Derkinderen, T. Savidge and M. Neunlist (2011). "Enteric glia promote intestinal mucosal healing via activation of focal adhesion kinase and release of proEGF." American journal of physiology. Gastrointestinal and liver physiology 300(6): G976-987.

Savidge, T. C., P. Urvil, N. Oezguen, K. Ali, A. Choudhury, V. Acharya, I. Pinchuk, A. G. Torres, R. D. English, J. E. Wiktorowicz, M. Loeffelholz, R. Kumar, L. Shi, W. Nie, W. Braun, B. Herman, A. Hausladen, H. Feng, J. S. Stamler and C. Pothoulakis (2011). "Host S-nitrosylation inhibits clostridial small molecule-activated glucosylating toxins." Nature medicine 17(9): 1136-1141.

Savidge, T. C. (2011). "S-nitrosothiol signals in the enteric nervous system: lessons learnt from big brother." Frontiers in neuroscience 5: 31.

Savidge, T. C. (2011). "Glia and NO nicotine: a perfect harmony for secretory control." The Journal of physiology 589(Pt 15): 3685-3686.

Flamant, M., P. Aubert, M. Rolli-Derkinderen, A. Bourreille, M. R. Neunlist, M. M. Mahe, G. Meurette, B. Marteyn, T. Savidge, J. P. Galmiche, P. J. Sansonetti and M. Neunlist (2011). "Enteric glia protect against Shigella flexneri invasion in intestinal epithelial cells: a role for S-nitrosoglutathione." Gut 60(4): 473-484.

Sun, X., T. Savidge and H. Feng (2010). "The enterotoxicity of Clostridium difficile toxins." Toxins 2(7): 1848-1880.

Chaniotou, Z., P. Giannogonas, S. Theoharis, T. Teli, J. Gay, T. Savidge, Y. Koutmani, J. Brugni, E. Kokkotou, C. Pothoulakis and K. P. Karalis (2010). "Corticotropin-releasing factor regulates TLR4 expression in the colon and protects mice from colitis." Gastroenterology 139(6): 2083-2092.

Kokkotou, E., D. O. Espinoza, D. Torres, I. Karagiannides, S. Kosteletos, T. Savidge, M. O'Brien and C. Pothoulakis (2009). "Melanin-concentrating hormone (MCH) modulates C difficile toxin A-mediated enteritis in mice." Gut 58(1): 34-40.

Neunlist, M., L. Van Landeghem, A. Bourreille and T. Savidge (2008). "Neuro-glial crosstalk in inflammatory bowel disease." Journal of internal medicine 263(6): 577-583.

Savidge, T. C., M. V. Sofroniew and M. Neunlist (2007). "Starring roles for astroglia in barrier pathologies of gut and brain." Laboratory investigation; a journal of technical methods and pathology 87(8): 731-736.

Savidge, T. C., P. Newman, C. Pothoulakis, A. Ruhl, M. Neunlist, A. Bourreille, R. Hurst and M. V. Sofroniew (2007). "Enteric glia regulate intestinal barrier function and inflammation via release of S-nitrosoglutathione." Gastroenterology 132(4): 1344-1358.

Savidge, T. C. (2007). "MIND the gap: an astroglial perspective on barrier regulation." Neuron glia biology 3(3): 191-197.

Neunlist, M., P. Aubert, S. Bonnaud, L. Van Landeghem, E. Coron, T. Wedel, P. Naveilhan, A. Ruhl, B. Lardeux, T. Savidge, F. Paris and J. P. Galmiche (2007). "Enteric glia inhibit intestinal epithelial cell proliferation partly through a TGF-beta1-dependent pathway." American journal of physiology. Gastrointestinal and liver physiology 292(1): G231-241.

Moss, A. C., P. Anton, T. Savidge, P. Newman, A. S. Cheifetz, J. Gay, S. Paraschos, M. W. Winter, M. P. Moyer, K. Karalis, E. Kokkotou and C. Pothoulakis (2007). "Urocortin II mediates pro-inflammatory effects in human colonocytes via corticotropin-releasing hormone receptor 2alpha." Gut 56(9): 1210-1217.

Hoogerwerf, W. A., H. L. Hellmich, G. Cornelissen, F. Halberg, V. B. Shahinian, J. Bostwick, T. C. Savidge and V. M. Cassone (2007). "Clock gene expression in the murine gastrointestinal tract: endogenous rhythmicity and effects of a feeding regimen." Gastroenterology 133(4): 1250-1260.

Savidge, T. C., P. G. Newman, W. H. Pan, M. Q. Weng, H. N. Shi, B. A. McCormick, A. Quaroni and W. A. Walker (2006). "Lipopolysaccharide-induced human enterocyte tolerance to cytokine-mediated interleukin-8 production may occur independently of TLR-4/MD-2 signaling." Pediatric research 59(1): 89-95.

Kim, H., S. H. Rhee, E. Kokkotou, X. Na, T. Savidge, M. P. Moyer, C. Pothoulakis and J. T. LaMont (2005). "Clostridium difficile toxin A regulates inducible cyclooxygenase-2 and prostaglandin E2 synthesis in colonocytes via reactive oxygen species and activation of p38 MAPK." The Journal of biological chemistry 280(22): 21237-21245.

Mrsny, R. J., A. T. Gewirtz, D. Siccardi, T. Savidge, B. P. Hurley, J. L. Madara and B. A. McCormick (2004). "Identification of hepoxilin A3 in inflammatory events: a required role in neutrophil migration across intestinal epithelia." Proceedings of the National Academy of Sciences of the United States of America 101(19): 7421-7426.

Claud, E. C., L. Lu, P. M. Anton, T. Savidge, W. A. Walker and B. J. Cherayil (2004). "Developmentally regulated IkappaB expression in intestinal epithelium and susceptibility to flagellin-induced inflammation." Proceedings of the National Academy of Sciences of the United States of America 101(19): 7404-7408.

Savidge, T. C., W. H. Pan, P. Newman, M. O'Brien, P. M. Anton and C. Pothoulakis (2003). "Clostridium difficile toxin B is an inflammatory enterotoxin in human intestine." Gastroenterology 125(2): 413-420.

Lu, L., M. E. Baldeon, T. Savidge, C. Pothoulakis and W. A. Walker (2003). "Development of microbial-human enterocyte interaction: cholera toxin." Pediatric research 54(2): 212-218.

Claud, E. C., T. Savidge and W. A. Walker (2003). "Modulation of human intestinal epithelial cell IL-8 secretion by human milk factors." Pediatric research 53(3): 419-425.

Cabarrocas, J., T. C. Savidge and R. S. Liblau (2003). "Role of enteric glial cells in inflammatory bowel disease." Glia 41(1): 81-93.

Buisine, M. P., J. P. Aubert, W. A. Walker and T. C. Savidge (2003). "Developmental patterns of mucin gene expression in human fetal small intestinal xenografts maintained in severe-combined immunodeficient mice." Pediatric research 53(6): 898-904.

Dai, D., N. N. Nanthakumar, T. C. Savidge, D. S. Newburg and W. A. Walker (2002). "Region-specific ontogeny of alpha-2,6-sialyltransferase during normal and cortisone-induced maturation in mouse intestine." American journal of physiology. Gastrointestinal and liver physiology 282(3): G480-490.

Savidge, T. C., D. C. Lowe and W. A. Walker (2001). "Developmental regulation of intestinal epithelial hydrolase activity in human fetal jejunal xenografts maintained in severe-combined immunodeficient mice." Pediatric research 50(2): 196-202.

Cornet, A., T. C. Savidge, J. Cabarrocas, W. L. Deng, J. F. Colombel, H. Lassmann, P. Desreumaux and R. S. Liblau (2001). "Enterocolitis induced by autoimmune targeting of enteric glial cells: a possible mechanism in Crohn's disease?" Proceedings of the National Academy of Sciences of the United States of America 98(23): 13306-13311.

Savidge, T. C. (2000). "Gastrointestinal response to food: artificial or not?" Journal of pediatric gastroenterology and nutrition 31(2): 118-120.

Murch, S. H., C. R. Fertleman, C. Rodrigues, G. Morgan, N. J. Klein, N. Meadows, T. C. Savidge, A. D. Phillips and J. A. Walker-Smith (1999). "Autoimmune enteropathy with distinct mucosal features in T-cell activation deficiency: the contribution of T cells to the mucosal lesion." Journal of pediatric gastroenterology and nutrition 28(4): 393-399.

Montagne, L., R. Toullec, T. Savidge and J. P. Lalles (1999). "Morphology and enzyme activities of the small intestine are modulated by dietary protein source in the preruminant calf." Reproduction, nutrition, development 39(4): 455-466.

Lowe, D. C., T. C. Savidge, D. Pickard, L. Eckmann, M. F. Kagnoff, G. Dougan and S. N. Chatfield (1999). "Characterization of candidate live oral Salmonella typhi vaccine strains harboring defined mutations in aroA, aroC, and htrA." Infection and immunity 67(2): 700-707.

Laurent, F., M. F. Kagnoff, T. C. Savidge, M. Naciri and L. Eckmann (1998). "Human intestinal epithelial cells respond to Cryptosporidium parvum infection with increased prostaglandin H synthase 2 expression and prostaglandin E2 and F2alpha production." Infection and immunity 66(4): 1787-1790.

Kim, J. M., L. Eckmann, T. C. Savidge, D. C. Lowe, T. Witthoft and M. F. Kagnoff (1998). "Apoptosis of human intestinal epithelial cells after bacterial invasion." The Journal of clinical investigation 102(10): 1815-1823.

Bush, T. G., T. C. Savidge, T. C. Freeman, H. J. Cox, E. A. Campbell, L. Mucke, M. H. Johnson and M. V. Sofroniew (1998). "Fulminant jejuno-ileitis following ablation of enteric glia in adult transgenic mice." Cell 93(2): 189-201.

Buisine, M. P., L. Devisme, T. C. Savidge, C. Gespach, B. Gosselin, N. Porchet and J. P. Aubert (1998). "Mucin gene expression in human embryonic and fetal intestine." Gut 43(4): 519-524.

Whyte, A., D. Locke, T. Savidge and S. T. Licence (1997). "Pig lymphocytes utilise mouse MAdCAM-1 to enter fetal gut xenografts in SCID mice." Cellular immunology 182(1): 38-44.

Laurent, F., L. Eckmann, T. C. Savidge, G. Morgan, C. Theodos, M. Naciri and M. F. Kagnoff (1997). "Cryptosporidium parvum infection of human intestinal epithelial cells induces the polarized secretion of C-X-C chemokines." Infection and immunity 65(12): 5067-5073.

Eckmann, L., W. F. Stenson, T. C. Savidge, D. C. Lowe, K. E. Barrett, J. Fierer, J. R. Smith and M. F. Kagnoff (1997). "Role of intestinal epithelial cells in the host secretory response to infection by invasive bacteria. Bacterial entry induces epithelial prostaglandin h synthase-2 expression and prostaglandin E2 and F2alpha production." The Journal of clinical investigation 100(2): 296-309.

Savidge, T. C., A. N. Shmakov, J. A. Walker-Smith and A. D. Phillips (1996). "Epithelial cell proliferation in childhood enteropathies." Gut 39(2): 185-193.

Savidge, T. C. (1996). "The life and times of an intestinal M cell." Trends in microbiology 4(8): 301-306.

Huang, G. T., L. Eckmann, T. C. Savidge and M. F. Kagnoff (1996). "Infection of human intestinal epithelial cells with invasive bacteria upregulates apical intercellular adhesion molecule-1 (ICAM)-1) expression and neutrophil adhesion." The Journal of clinical investigation 98(2): 572-583.

Shmakov, A. N. and T. C. Savidge (1995). "Cellular proliferation in the crypt epithelium of human small intestinal xenografts." Epithelial cell biology 4(3): 104-112.

Shmakov, A. N., A. L. Morey, D. J. Ferguson, K. A. Fleming, J. A. O'Brien and T. C. Savidge (1995). "Conventional patterns of human intestinal proliferation in a severe-combined immunodeficient xenograft model." Differentiation; research in biological diversity 59(5): 321-330.

Savidge, T. C., J. A. Walker-Smith and A. D. Phillips (1995). "Intestinal proliferation in coeliac disease: looking into the crypt." Gut 36(3): 321-323.

Savidge, T. C., J. A. Walker-Smith and A. D. Phillips (1995). "Novel insights into human intestinal epithelial cell proliferation in health and disease using confocal microscopy." Gut 36(3): 369-374.

Savidge, T. C., M. W. Smith and P. S. James (1995). "A confocal microscopical analysis of Peyer's patch membranous (M) cell and lymphocyte interactions in the scid mouse." Advances in experimental medicine and biology 371A: 243-245.

Savidge, T. C. and M. W. Smith (1995). "Evidence that membranous (M) cell genesis is immuno-regulated." Advances in experimental medicine and biology 371A: 239-241.

Savidge, T. C. and A. Shmakova (1995). "Human gastrointestinal drug delivery; an experimental chimeric approach." Journal of drug targeting 3(1): 71-74.

Savidge, T. C., A. L. Morey, D. J. Ferguson, K. A. Fleming, A. N. Shmakov and A. D. Phillips (1995). "Human intestinal development in a severe-combined immunodeficient xenograft model." Differentiation; research in biological diversity 58(5): 361-371.

Savidge, T. C., M. W. Smith, S. Mayel-Afshar, A. J. Collins and T. C. Freeman (1994). "Selective regulation of epithelial gene expression in rabbit Peyer's patch tissue." Pflugers Archiv : European journal of physiology 428(3-4): 391-399.

Jepson, M. A., N. L. Simmons, T. C. Savidge, P. S. James and B. H. Hirst (1993). "Selective binding and transcytosis of latex microspheres by rabbit intestinal M cells." Cell and tissue research 271(3): 399-405.

Brown, D., M. W. Smith, P. S. James and T. C. Savidge (1993). "Possible models describing enterocyte replacement in mouse Peyer's patch follicle-associated epithelial tissue." Epithelial cell biology 2(4): 135-142.

Porta, C., P. S. James, A. D. Phillips, T. C. Savidge, M. W. Smith and D. Cremaschi (1992). "Confocal analysis of fluorescent bead uptake by mouse Peyer's patch follicle-associated M cells." Experimental physiology 77(6): 929-932.

Savidge, T. C., M. W. Smith, P. S. James and P. Aldred (1991). "Salmonella-induced M-cell formation in germ-free mouse Peyer's patch tissue." The American journal of pathology 139(1): 177-184.

Savidge, T. C., M. W. Smith and P. J. Kilshaw (1990). "Possible lymphocyte effects on lactase expression by mouse jejunal enterocytes." Experimental physiology 75(1): 111-113.

Savidge, T. A. and M. Cole (1975). "Penicillin acylase (bacterial)." Methods in enzymology 43: 705-721.

Cole, M., T. Savidge and H. Vanderhaeghe (1975). "Penicillin acylase (assay)." Methods in enzymology 43: 698-705.


Book Chapters


Savidge TC, Pothoulakis C (Editors). Microbial Imaging in Methods in Microbiology Volume 34. London, Elsevier Academic Press; November 2004.

Savidge T, Neunlist M, Sofroniew M. Glial cells and barrier functions: another gut-brain paradigm. In: Glial Cells in Health and Disease. Medimond S.r.l. pp 41-46 (2007).

Savidge TC. Ectopic transplantation techniques for evaluating gastrointestinal development of the Gastrointestinal Tract. In Development of the Gastrointestinal Tract. Eds; Sanderson IR, Walker WA. Hamilton: Decker BC Publishers 307-319 (1999) (citation: 2).

Savidge TC, Shmakov AN, Walker-Smith JA, Phillips AD. Intestinal proliferation and infection in childhood. In: Holt F, Winton D, Wright N, eds. The gut as a model for cell and molecular biology. Dordrecht: Kluwer Academic Publishers, 110-120 (1997).

Savidge TC, James PS, Smith MW. A confocal microscopical analysis of Peyer's patch M cell-lymphocyte interactions in the scid mouse. In: Mestecky J et al, eds. Advances in Mucosal Immunology, Part A. New York: Plenum Publishing Co. 243-245 (1995) (citation: 4).

Savidge TC, Smith MW. Evidence that membranous (M) cell genesis is immuno-regulated. In: Mestecky J et al, eds. Advances in Mucosal Immunology, Part A. New York: Plenum Publishing Co. 239-241 (1995) (citation: 33).

Savidge TC, M.W. Smith MW, P.S. James PS, Aldred P. Salmonella increase cell numbers in mouse Peyer's patch follicle associated epithelium. In: MacDonald TT et al, eds. Advances in Mucosal Immunology. Dordrecht: Kluwer Academic Publishers, 95-98 (1990).