Alain P. Gobert, Ph.D.

Research Associate Professor

alain.p.gobert@vanderbilt.edu
Faculty Appointments
Research Associate Professor of Medicine
Education
Ph.D., Université Bordeaux 1, Bordeaux, FranceB.S., University of Orleans, Orleans, Foreign, FranceM.S., Université Bordeaux 1, Bordeaux, France
Office Address
1015 MRB IV
TN
Research Description
Dr. Gobert has a particular interest in the study of host/pathogen interactions and has significant experience in the study of nitrosative stress as a mediator of the immune response. After a PhD in Chemistry from the University of Bordeaux, France, Dr. Gobert completed postdoctoral training at the University of Maryland, Baltimore, where he conducted research on the role and the regulation of nitric oxide (NO) during infectious diseases of the gastrointestinal tract. More particularly, his work uncovered the essential role of arginine metabolism in the control of H. pylori infection, inflammation and gastric cancer. He was then awarded a postdoctoral fellowship from The Pasteur Institute in Paris, France, to pursue his research on the inflammation associated with the gastric pathogen Helicobacter pylori. He began his independent research program at the French National Institute for Agricultural Research in 2003 where he and his group highlighted the molecular mechanisms by which NO regulates cellular attachment and toxin production by intestinal pathogenic bacteria. After a three-year sabbatical in the Division of Gastroenterology at Vanderbilt University Medical Center, Dr. Gobert is now joining the new Center for Mucosal Inflammation and Cancer headed by Pr. Keith T. Wilson. His work will yield important insights into how pathogen-induced inflammation leads to carcinogenesis and will have directly translatable utility in therapeutic strategies to treat gastric cancer.
Research Keywords
Nitric Oxide; Polyamines; Inflammation; Macrophage; Epithelial Cell; Bacteria; Pathogen; Carcinogenesis.
Publications
Singh K, Coburn LA, Asim M, Barry DP, Allaman MM, Shi C, Washington MK, Luis PB, Schneider C, Delgado AG, Piazuelo MB, Cleveland JL, Gobert AP, Wilson KT. Ornithine Decarboxylase in Macrophages Exacerbates Colitis and Promotes Colitis-Associated Colon Carcinogenesis by Impairing M1 Immune Responses. Cancer Res [print-electronic]. 2018 Aug 8/1/2018; 78(15): 4303-15. PMID: 29853605, PMCID: PMC6072585, PII: 0008-5472.CAN-18-0116, DOI: 10.1158/0008-5472.CAN-18-0116, ISSN: 1538-7445.

Choksi YA, Reddy VK, Singh K, Barrett CW, Short SP, Parang B, Keating CE, Thompson JJ, Verriere TG, Brown RE, Piazuelo MB, Bader DM, Washington MK, Mittal MK, Brand T, Gobert AP, Coburn LA, Wilson KT, Williams CS. BVES is required for maintenance of colonic epithelial integrity in experimental colitis by modifying intestinal permeability. Mucosal Immunol [print-electronic]. 2018 Jun 6/15/2018; PMID: 29907869, PII: 10.1038/s41385-018-0043-2, DOI: 10.1038/s41385-018-0043-2, ISSN: 1935-3456.

Gobert AP, Al-Greene NT, Singh K, Coburn LA, Sierra JC, Verriere TG, Luis PB, Schneider C, Asim M, Allaman MM, Barry DP, Cleveland JL, Destefano Shields CE, Casero RA, Washington MK, Piazuelo MB, Wilson KT. Distinct Immunomodulatory Effects of Spermine Oxidase in Colitis Induced by Epithelial Injury or Infection. Front Immunol. 2018; 9: 1242. PMID: 29922289, PMCID: PMC5996034, DOI: 10.3389/fimmu.2018.01242, ISSN: 1664-3224.

Nzoumbou-Boko R, De Muylder G, Semballa S, Lecordier L, Dauchy FA, Gobert AP, Holzmuller P, Lemesre JL, Bras-Gonçalves R, Barnabé C, Courtois P, Daulouède S, Beschin A, Pays E, Vincendeau P. Trypanosoma musculi Infection in Mice Critically Relies on Mannose Receptor-Mediated Arginase Induction by a TbKHC1 Kinesin H Chain Homolog. J. Immunol [print-electronic]. 2017 Sep 9/1/2017; 199(5): 1762-71. PMID: 28739879, PII: jimmunol.1700179, DOI: 10.4049/jimmunol.1700179, ISSN: 1550-6606.

Hardbower DM, Coburn LA, Asim M, Singh K, Sierra JC, Barry DP, Gobert AP, Piazuelo MB, Washington MK, Wilson KT. EGFR-mediated macrophage activation promotes colitis-associated tumorigenesis. Oncogene [print-electronic]. 2017 Jul 7/6/2017; 36(27): 3807-19. PMID: 28263971, PMCID: PMC5501754, PII: onc201723, DOI: 10.1038/onc.2017.23, ISSN: 1476-5594.

Gobert AP, Wilson KT. Effect of CO2 on Peroxynitrite-Mediated Bacteria Killing: Response to Tsikas et al [letter]. Trends Microbiol [print-electronic]. 2017 Jun 6/10/2017; PMID: 28610877, PII: S0966-842X(17)30123-3, DOI: 10.1016/j.tim.2017.05.009, ISSN: 1878-4380.

Sierra JC, Asim M, Verriere TG, Piazuelo MB, Suarez G, Romero-Gallo J, Delgado AG, Wroblewski LE, Barry DP, Peek RM, Gobert AP, Wilson KT. Epidermal growth factor receptor inhibition downregulates Helicobacter pylori-induced epithelial inflammatory responses, DNA damage and gastric carcinogenesis. Gut [print-electronic]. 2017 May 5/4/2017; PMID: 28473630, PII: gutjnl-2016-312888, DOI: 10.1136/gutjnl-2016-312888, ISSN: 1468-3288.

Hardbower DM, Asim M, Luis PB, Singh K, Barry DP, Yang C, Steeves MA, Cleveland JL, Schneider C, Piazuelo MB, Gobert AP, Wilson KT. Ornithine decarboxylase regulates M1 macrophage activation and mucosal inflammation via histone modifications. Proc. Natl. Acad. Sci. U.S.A [print-electronic]. 2017 Jan 1/31/2017; 114(5): E751-E760. PMID: 28096401, PMCID: PMC5293075, PII: 1614958114, DOI: 10.1073/pnas.1614958114, ISSN: 1091-6490.

Gobert AP, Wilson KT. Human and Helicobacter pylori Interactions Determine the Outcome of Gastric Diseases. Curr. Top. Microbiol. Immunol. 2017; 400: 27-52. PMID: 28124148, PMCID: PMC5316293, DOI: 10.1007/978-3-319-50520-6_2, ISSN: 0070-217X.

Gobert AP, Sagrestani G, Delmas E, Wilson KT, Verriere TG, Dapoigny M, Del'homme C, Bernalier-Donadille A. The human intestinal microbiota of constipated-predominant irritable bowel syndrome patients exhibits anti-inflammatory properties. Sci Rep. 2016 Dec 12/16/2016; 6: 39399. PMID: 27982124, PMCID: PMC5159846, PII: srep39399, DOI: 10.1038/srep39399, ISSN: 2045-2322.

Singh K, Al-Greene NT, Verriere TG, Coburn LA, Asim M, Barry DP, Allaman MM, Hardbower DM, Delgado AG, Piazuelo MB, Vallance BA, Gobert AP, Wilson KT. The L-Arginine Transporter Solute Carrier Family 7 Member 2 Mediates the Immunopathogenesis of Attaching and Effacing Bacteria. PLoS Pathog. 2016 Oct; 12(10): e1005984. PMID: 27783672, PMCID: PMC5081186, PII: PPATHOGENS-D-16-01126, DOI: 10.1371/journal.ppat.1005984, ISSN: 1553-7374.

Gobert AP, Wilson KT. Polyamine- and NADPH-dependent generation of ROS during Helicobacter pylori infection: A blessing in disguise. Free Radic. Biol. Med [print-electronic]. 2016 Sep 9/25/2016; PMID: 27682363, PII: S0891-5849(16)30435-X, DOI: 10.1016/j.freeradbiomed.2016.09.024, ISSN: 1873-4596.

Monteiro R, Ageorges V, Rojas-Lopez M, Schmidt H, Weiss A, Bertin Y, Forano E, Jubelin G, Henderson IR, Livrelli V, Gobert AP, Rosini R, Soriani M, Desvaux M. A secretome view of colonisation factors in Shiga toxin-encoding Escherichia coli (STEC): from enterohaemorrhagic E. coli (EHEC) to related enteropathotypes. FEMS Microbiol. Lett [print-electronic]. 2016 Aug; 363(16): PMID: 27465489, PII: fnw179, DOI: 10.1093/femsle/fnw179, ISSN: 1574-6968.

Gobert AP, Wilson KT. The Immune Battle against Helicobacter pylori Infection: NO Offense. Trends Microbiol [print-electronic]. 2016 May; 24(5): 366-76. PMID: 26916789, PMCID: PMC4841705, PII: S0966-842X(16)00041-X, DOI: 10.1016/j.tim.2016.02.005, ISSN: 1878-4380.

Gobert AP, Verriere T, Asim M, Barry DP, Piazuelo MB, de Sablet T, Delgado AG, Bravo LE, Correa P, Peek RM, Chaturvedi R, Wilson KT. Heme oxygenase-1 dysregulates macrophage polarization and the immune response to Helicobacter pylori. J. Immunol [print-electronic]. 2014 Sep 9/15/2014; 193(6): 3013-22. PMID: 25108023, PMCID: PMC4171064, PII: jimmunol.1401075, DOI: 10.4049/jimmunol.1401075, ISSN: 1550-6606.

Branchu P, Matrat S, Vareille M, Garrivier A, Durand A, Crépin S, Harel J, Jubelin G, Gobert AP. NsrR, GadE, and GadX interplay in repressing expression of the Escherichia coli O157:H7 LEE pathogenicity island in response to nitric oxide. PLoS Pathog [print-electronic]. 2014 Jan; 10(1): e1003874. PMID: 24415940, PMCID: PMC3887101, PII: PPATHOGENS-D-13-00441, DOI: 10.1371/journal.ppat.1003874, ISSN: 1553-7374.

Gobert AP, Verriere T, de Sablet T, Peek RM, Chaturvedi R, Wilson KT. Haem oxygenase-1 inhibits phosphorylation of the Helicobacter pylori oncoprotein CagA in gastric epithelial cells. Cell. Microbiol [print-electronic]. 2013 Jan; 15(1): 145-56. PMID: 23051580, PMCID: PMC3524338, DOI: 10.1111/cmi.12039, ISSN: 1462-5822.

Gobert AP, Wilson KT. Editorial: Orchestration of macrophage polarization by polyamines [editorial]. J. Leukoc. Biol. 2012 May; 91(5): 677-9. PMID: 22547131, PMCID: PMC3336771, PII: 91/5/677, DOI: 10.1189/jlb.0112047, ISSN: 1938-3673.

Chaturvedi R, de Sablet T, Coburn LA, Gobert AP, Wilson KT. Arginine and polyamines in Helicobacter pylori-induced immune dysregulation and gastric carcinogenesis. Amino Acids [print-electronic]. 2012 Feb; 42(2-3): 627-40. PMID: 21874531, PMCID: PMC3258477, DOI: 10.1007/s00726-011-1038-4, ISSN: 1438-2199.

Gobert AP, Asim M, Piazuelo MB, Verriere T, Scull BP, de Sablet T, Glumac A, Lewis ND, Correa P, Peek RM, Chaturvedi R, Wilson KT. Disruption of nitric oxide signaling by Helicobacter pylori results in enhanced inflammation by inhibition of heme oxygenase-1. J. Immunol [print-electronic]. 2011 Nov 11/15/2011; 187(10): 5370-9. PMID: 21987660, PMCID: PMC3208050, PII: jimmunol.1102111, DOI: 10.4049/jimmunol.1102111, ISSN: 1550-6606.

Chaturvedi R, Asim M, Romero-Gallo J, Barry DP, Hoge S, de Sablet T, Delgado AG, Wroblewski LE, Piazuelo MB, Yan F, Israel DA, Casero RA, Correa P, Gobert AP, Polk DB, Peek RM, Wilson KT. Spermine oxidase mediates the gastric cancer risk associated with Helicobacter pylori CagA. Gastroenterology [print-electronic]. 2011 Nov; 141(5): 1696-708.e1. PMID: 21839041, PMCID: PMC3202654, PII: S0016-5085(11)01080-8, DOI: 10.1053/j.gastro.2011.07.045, ISSN: 1528-0012.

Lewis ND, Asim M, Barry DP, de Sablet T, Singh K, Piazuelo MB, Gobert AP, Chaturvedi R, Wilson KT. Immune evasion by Helicobacter pylori is mediated by induction of macrophage arginase II. J. Immunol [print-electronic]. 2011 Mar 3/15/2011; 186(6): 3632-41. PMID: 21296975, PMCID: PMC3069806, PII: jimmunol.1003431, DOI: 10.4049/jimmunol.1003431, ISSN: 1550-6606.

Barry DP, Asim M, Scull BP, Piazuelo MB, de Sablet T, Lewis ND, Coburn LA, Singh K, Ellies LG, Gobert AP, Chaturvedi R, Wilson KT. Cationic amino acid transporter 2 enhances innate immunity during Helicobacter pylori infection. PLoS ONE [print-electronic]. 2011; 6(12): e29046. PMID: 22194986, PMCID: PMC3237590, PII: PONE-D-11-18825, DOI: 10.1371/journal.pone.0029046, ISSN: 1932-6203.

Gobert AP, Chaturvedi R, Wilson KT. Methods to evaluate alterations in polyamine metabolism caused by Helicobacter pylori infection. Methods Mol. Biol. 2011; 720: 409-25. PMID: 21318889, PMCID: PMC3069756, DOI: 10.1007/978-1-61779-034-8_26, ISSN: 1940-6029.

Chaturvedi R, Asim M, Hoge S, Lewis ND, Singh K, Barry DP, de Sablet T, Piazuelo MB, Sarvaria AR, Cheng Y, Closs EI, Casero RA, Gobert AP, Wilson KT. Polyamines Impair Immunity to Helicobacter pylori by Inhibiting L-Arginine Uptake Required for Nitric Oxide Production. Gastroenterology [print-electronic]. 2010 Nov; 139(5): 1686-98, 1698.e1. PMID: 20600019, PMCID: PMC2967614, PII: S0016-5085(10)01003-6, DOI: 10.1053/j.gastro.2010.06.060, ISSN: 1528-0012.

Asim M, Chaturvedi R, Hoge S, Lewis ND, Singh K, Barry DP, Algood HS, de Sablet T, Gobert AP, Wilson KT. Helicobacter pylori induces ERK-dependent formation of a phospho-c-Fos c-Jun activator protein-1 complex that causes apoptosis in macrophages. J. Biol. Chem [print-electronic]. 2010 Jun 6/25/2010; 285(26): 20343-57. PMID: 20410304, PMCID: PMC2888446, PII: M110.116988, DOI: 10.1074/jbc.M110.116988, ISSN: 1083-351X.

Lewis ND, Asim M, Barry DP, Singh K, de Sablet T, Boucher JL, Gobert AP, Chaturvedi R, Wilson KT. Arginase II restricts host defense to Helicobacter pylori by attenuating inducible nitric oxide synthase translation in macrophages. J. Immunol [print-electronic]. 2010 Mar 3/1/2010; 184(5): 2572-82. PMID: 20097867, PMCID: PMC2841360, PII: jimmunol.0902436, DOI: 10.4049/jimmunol.0902436, ISSN: 1550-6606.

de Sablet T, Chassard C, Bernalier-Donadille A, Vareille M, Gobert AP, Martin C. Human microbiota-secreted factors inhibit shiga toxin synthesis by enterohemorrhagic Escherichia coli O157:H7. Infect. Immun [print-electronic]. 2009 Feb; 77(2): 783-90. PMID: 19064636, PMCID: PMC2632037, PII: IAI.01048-08, DOI: 10.1128/IAI.01048-08, ISSN: 1098-5522.

Vareille M, Rannou F, Thélier N, Glasser AL, de Sablet T, Martin C, Gobert AP. Heme oxygenase-1 is a critical regulator of nitric oxide production in enterohemorrhagic Escherichia coli-infected human enterocytes. J. Immunol. 2008 Apr 4/15/2008; 180(8): 5720-6. PMID: 18390757, PII: 180/8/5720, ISSN: 0022-1767.

Gobert AP, Coste A, Guzman CA, Vareille M, Hindré T, de Sablet T, Girardeau JP, Martin C. Modulation of chemokine gene expression by Shiga-toxin producing Escherichia coli belonging to various origins and serotypes. Microbes Infect [print-electronic]. 2008 Feb; 10(2): 159-65. PMID: 18248761, PII: S1286-4579(07)00339-5, DOI: 10.1016/j.micinf.2007.10.018, ISSN: 1286-4579.

de Sablet T, Bertin Y, Vareille M, Girardeau JP, Garrivier A, Gobert AP, Martin C. Differential expression of stx2 variants in Shiga toxin-producing Escherichia coli belonging to seropathotypes A and C. Microbiology (Reading, Engl.). 2008 Jan; 154(Pt 1): 176-86. PMID: 18174136, PII: 154/1/176, DOI: 10.1099/mic.0.2007/009704-0, ISSN: 1350-0872.

Gobert AP, Vareille M, Glasser AL, Hindré T, de Sablet T, Martin C. Shiga toxin produced by enterohemorrhagic Escherichia coli inhibits PI3K/NF-kappaB signaling pathway in globotriaosylceramide-3-negative human intestinal epithelial cells. J. Immunol. 2007 Jun 6/15/2007; 178(12): 8168-74. PMID: 17548655, PII: 178/12/8168, ISSN: 0022-1767.

Vareille M, de Sablet T, Hindré T, Martin C, Gobert AP. Nitric oxide inhibits Shiga-toxin synthesis by enterohemorrhagic Escherichia coli. Proc. Natl. Acad. Sci. U.S.A [print-electronic]. 2007 Jun 6/12/2007; 104(24): 10199-204. PMID: 17537918, PMCID: PMC1891265, PII: 0702589104, DOI: 10.1073/pnas.0702589104, ISSN: 0027-8424.

Gobert AP, Wilson KT, Martin C. Cellular responses to attaching and effacing bacteria: activation and implication of the innate immune system. Arch. Immunol. Ther. Exp. (Warsz.). 2005 May; 53(3): 234-44. PMID: 15995584, PII: 7450, ISSN: 0004-069X.

Bussière FI, Chaturvedi R, Cheng Y, Gobert AP, Asim M, Blumberg DR, Xu H, Kim PY, Hacker A, Casero RA, Wilson KT. Spermine causes loss of innate immune response to Helicobacter pylori by inhibition of inducible nitric-oxide synthase translation. J. Biol. Chem [print-electronic]. 2005 Jan 1/28/2005; 280(4): 2409-12. PMID: 15548540, PII: C400498200, DOI: 10.1074/jbc.C400498200, ISSN: 0021-9258.

Chaturvedi R, Cheng Y, Asim M, Bussière FI, Xu H, Gobert AP, Hacker A, Casero RA, Wilson KT. Induction of polyamine oxidase 1 by Helicobacter pylori causes macrophage apoptosis by hydrogen peroxide release and mitochondrial membrane depolarization. J. Biol. Chem [print-electronic]. 2004 Sep 9/17/2004; 279(38): 40161-73. PMID: 15247269, PII: M401370200, DOI: 10.1074/jbc.M401370200, ISSN: 0021-9258.

Gobert AP, Cheng Y, Akhtar M, Mersey BD, Blumberg DR, Cross RK, Chaturvedi R, Drachenberg CB, Boucher JL, Hacker A, Casero RA, Wilson KT. Protective role of arginase in a mouse model of colitis. J. Immunol. 2004 Aug 8/1/2004; 173(3): 2109-17. PMID: 15265947, PII: 173/3/2109, ISSN: 0022-1767.

Duleu S, Vincendeau P, Courtois P, Semballa S, Lagroye I, Daulouède S, Boucher JL, Wilson KT, Veyret B, Gobert AP. Mouse strain susceptibility to trypanosome infection: an arginase-dependent effect. J. Immunol. 2004 May 5/15/2004; 172(10): 6298-303. PMID: 15128819, ISSN: 0022-1767.

Gobert AP, Bambou JC, Werts C, Balloy V, Chignard M, Moran AP, Ferrero RL. Helicobacter pylori heat shock protein 60 mediates interleukin-6 production by macrophages via a toll-like receptor (TLR)-2-, TLR-4-, and myeloid differentiation factor 88-independent mechanism. J. Biol. Chem [print-electronic]. 2004 Jan 1/2/2004; 279(1): 245-50. PMID: 14573621, PII: M307858200, DOI: 10.1074/jbc.M307858200, ISSN: 0021-9258.

Meyer F, Ramanujam KS, Gobert AP, James SP, Wilson KT. Cutting edge: cyclooxygenase-2 activation suppresses Th1 polarization in response to Helicobacter pylori. J. Immunol. 2003 Oct 10/15/2003; 171(8): 3913-7. PMID: 14530307, ISSN: 0022-1767.

Vincendeau P, Gobert AP, Daulouède S, Moynet D, Mossalayi MD. Arginases in parasitic diseases. Trends Parasitol. 2003 Jan; 19(1): 9-12. PMID: 12488215, PII: S1471492202000107, ISSN: 1471-4922.

Gobert AP, Mersey BD, Cheng Y, Blumberg DR, Newton JC, Wilson KT. Cutting edge: urease release by Helicobacter pylori stimulates macrophage inducible nitric oxide synthase. J. Immunol. 2002 Jun 6/15/2002; 168(12): 6002-6. PMID: 12055207, ISSN: 0022-1767.

Gobert AP, Cheng Y, Wang JY, Boucher JL, Iyer RK, Cederbaum SD, Casero RA, Newton JC, Wilson KT. Helicobacter pylori induces macrophage apoptosis by activation of arginase II. J. Immunol. 2002 May 5/1/2002; 168(9): 4692-700. PMID: 11971019, ISSN: 0022-1767.

Gobert AP, McGee DJ, Akhtar M, Mendz GL, Newton JC, Cheng Y, Mobley HL, Wilson KT. Helicobacter pylori arginase inhibits nitric oxide production by eukaryotic cells: a strategy for bacterial survival. Proc. Natl. Acad. Sci. U.S.A. 2001 Nov 11/20/2001; 98(24): 13844-9. PMID: 11717441, PMCID: PMC61129, PII: 98/24/13844, DOI: 10.1073/pnas.241443798, ISSN: 0027-8424.

Gobert AP, Daulouede S, Lepoivre M, Boucher JL, Bouteille B, Buguet A, Cespuglio R, Veyret B, Vincendeau P. L-Arginine availability modulates local nitric oxide production and parasite killing in experimental trypanosomiasis. Infect. Immun. 2000 Aug; 68(8): 4653-7. PMID: 10899869, PMCID: PMC98402, ISSN: 0019-9567.

Gobert AP, Vincendeau P, Mossalayi D, Veyret B. Mechanism of extracellular thiol nitrosylation by N(2)O(3) produced by activated macrophages. Nitric Oxide. 1999 Dec; 3(6): 467-72. PMID: 10637125, PII: S1089-8603(99)90260-4, DOI: 10.1006/niox.1999.0260, ISSN: 1089-8603.

Gobert AP, Semballa S, Daulouede S, Lesthelle S, Taxile M, Veyret B, Vincendeau P. Murine macrophages use oxygen- and nitric oxide-dependent mechanisms to synthesize S-nitroso-albumin and to kill extracellular trypanosomes. Infect. Immun. 1998 Sep; 66(9): 4068-72. PMID: 9712749, PMCID: PMC108487, ISSN: 0019-9567.