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Vanderbilt-Ingram Cancer CenterVanderbilt-Ingram Cancer Center

 
Keith T.  Wilson

Keith T. Wilson, M.D.

Thomas F. Frist, Sr. Professor of Medicine (Gastroenterology, Hepatology & Nutrition)
Professor of Cancer Biology
Director of Research and Fellowship Training Program, Division of Gastroenterology, Hepatology, & Nutrition
Researcher

Contact Information:

Vanderbilt University Medical Center
1030C MRBIV
Nashville , TN 37232-0252
615-343-5675
Fax: 615-343-6229

Profile

An emerging concept over the last decade is that most gastrointestinal malignancies actually arise from chronic inflammation. In keeping with this concept I have made a major component of my research program how the dysregulation of mucosal immune responses can lead to neoplastic transformation.
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An emerging concept over the last decade is that most gastrointestinal malignancies actually arise from chronic inflammation. In keeping with this concept I have made a major component of my research program how the dysregulation of mucosal immune responses can lead to neoplastic transformation.

Exploding knowledge about Helicobacter pylori in the 1990's and the elegance of this area of investigation as a perfect model to study mucosal immunology caused me to study this area for the last 10 years. My work has focused on host response to the infection. These studies have involved the innate immune response and the identification of ways that this response is ineffective. In this context we have also elucidated several important mechanisms whereby the epithelial responses may also be inappropriate, leading to risk for cancer development. My laboratory seeks to unravel novel mechanisms for inflammation and cellular damage, which in the case of H. pylori infection leads to increased cancer risk. One such pathway that we have reported is that H. pylori specifically induces the enzyme spermine oxidase (SMO), originally known as polyamine oxidase 1, which selectively utilizes the polyamine spermine as substrate. Our studies showed that the generation of H2O2 by SMO results in mitochondrial membrane depolarization, cytochrome c release, caspase-3 activation, and apoptosis. Our work has also shown that spermine itself contributes to the inadequacy of the host response, by blocking iNOS translation and hence NO production that is needed for the killing of H. pylori. We have specifically reported that upregulation of SMO is a major source of oxidative stress in gastric epithelial cells that leads to both apoptosis and DNA damage. Our funded studies are focused on the role of SMO in inflammatory responses and the mechanisms of ODC and SMO gene promoter activation. We are now moving further into the direction of the role of SMO in cancer, since we will be working with carcinogenic strains of H. pylori developed at Vanderbilt and a mouse model of gastric cancer, hypergastrinemic INS-GAS mice.

My lab will also be investigating the role of SMO in colon cancer derived from inflammatory bowel disease and in esophageal cancer derived from Barrett's esophagus. We also have substantial experience working with COX-2 in inflammation-associated carcinogenesis in the case of Barrett's esophagus and H. pylori infection.

Education
  • B.A. Cornell University, 1982
  • M.D. Harvard Medical School, 1986
  • Residency, Internal Medicine, Case Western Reserve University Hospitals of Cleveland 1986-1989
  • Fellowship, Gastroenterology, University of Chicago, 1989-1993
Research Description

My laboratory is focused on gastrointestinal mucosal inflammation and carcinogenesis. We study the host immune response to the gastric pathogen Helicobacter pylori that causes peptic ulcer disease and gastric cancer. This includes the innate immune response in macrophages and the identification of ways that this response is ineffective. We have also elucidated mechanisms whereby epithelial responses are inappropriate, leading to risk for cancer development. We study novel mechanisms for inflammation and cellular/DNA damage, which leads to increased cancer risk.

We have reported that H. pylori induces the enzyme spermine oxidase (SMOX), originally known as polyamine oxidase 1, which utilizes the polyamine spermine as substrate. Generation of H2O2 by SMOX results in mitochondrial membrane depolarization, cytochrome c release, and apoptosis. Spermine itself contributes to the inadequacy of the host response, by blocking translation of inducible nitric oxide (NO) synthase (iNOS) and hence NO production that is needed for the killing of H. pylori. Upregulation of SMOX causes oxidative stress in gastric epithelial cells that leads to both apoptosis and DNA damage. Induction of ornithine decarboxylase (ODC) that generates polyamines also leads to apoptosis of macrophages, contributing to loss of host innate immunity to H. pylori. We have shown that induction of the transcription factor c-Myc by H. pylori enhances ODC transcription and has a causal role in macrophage apoptosis. We have also implicated formation of a specific AP-1 complex in the activation of c-Myc.

We are utilizing clinical material from a large cohort of human subjects from Colombia, South America where H. pylori infection prevalence is very high, but gastric cancer risk is 25-fold higher in the Andean mountains when compared to the coastal region. We have found that SMOX-dependent oxidative stress is increased in gastric epithelial cells in vivo in the subjects at high risk for gastric cancer and that H. pylori clinical strains from these subjects induce more SMOX and oxidative DNA damage both in vitro and in vivo in a gerbil model. Furthermore, inhibition of ODC or SMOX reduces gastric cancer in the gerbil model. Studies are ongoing to pursue the mechanisms involved in the differential induction of SMOX and DNA damage.

We are also pursuing studies on immune dysregulation in inflammatory bowel disease. This includes work on arginine availability/transport, polyamines, and nitric oxide. We have reported that levels of the amino acid L-arginine are increased in the serum of humans with ulcerative colitis. Because L-arginine is important in regulation of epithelial integrity and immune function a defect in the utilization of L-arginine could contribute to the disease pathogenesis. Consistent with this, we have shown that treatment with L-arginine improves colitis in mouse models and that mice lacking an inducible L-arginine transporter have increased disease activity.

Our funded studies are focused on:
1) Mechanisms of H. pylori induced DNA damage and immune dysregulation, with an emphasis on the effects of polyamines and their oxidation (PI, R01 grant)
2) The role oxidative and nitrosative stress in the development of gastric cancer in Colombia, and the importance of H. pylori strains from regions of low and high gastric cancer risk in modulation of host responses (PI, P01 grant)
3) Importance of arginine metabolism in the immune response to H. pylori (PI, VA Merit Review Grant)
4) Role of EGFR signaling and polyamines in epithelial dysfunction in H. pylori infection and carcinogenesis (PI, project on P01)
5) Inhibition of polyamine synthesis with difluoromethylornithine in human subjects in Colombia and Honduras with precancerous gastric lesions (PI, R01 grant).
6) Arginine and other amino acids as immunomodulatory agents and potential therapies in colitis and colitis-associated cancer (PI, R01 grant)
7) Clinical study on amino acids in ulcerative colitis (PI- R01 supplement; funding completed, analysis ongoing)

Publications
  • Murray-Stewart T, Sierra JC, Piazuelo MB, Mera RM, Chaturvedi R, Bravo LE, Correa P, Schneider BG, Wilson KT, Casero RA. Epigenetic silencing of miR-124 prevents spermine oxidase regulation: implications for Helicobacter pylori-induced gastric cancer. Oncogene [print-electronic]. 2016 Apr 4/4/2016; PMID: 27041578, PII: onc201691, DOI: 10.1038/onc.2016.91, ISSN: 1476-5594.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/27041578.
  • Gobert AP, Wilson KT. The Immune Battle against Helicobacter pylori Infection: NO Offense. Trends Microbiol [print-electronic]. 2016 Feb 2/22/2016; PMID: 26916789, PII: S0966-842X(16)00041-X, DOI: 10.1016/j.tim.2016.02.005, ISSN: 1878-4380.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/26916789.
  • Garay J, Piazuelo MB, Majumdar S, Li L, Trillo-Tinoco J, Del Valle L, Schneider BG, Delgado AG, Wilson KT, Correa P, Zabaleta J. The homing receptor CD44 is involved in the progression of precancerous gastric lesions in patients infected with Helicobacter pylori and in development of mucous metaplasia in mice. Cancer Lett [print-electronic]. 2016 Feb 2/1/2016; 371(1): 90-8. PMID: 26639196, PII: S0304-3835(15)00705-3, DOI: 10.1016/j.canlet.2015.10.037, ISSN: 1872-7980.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/26639196.
  • Yang I, Woltemate S, Piazuelo MB, Bravo LE, Yepez MC, Romero-Gallo J, Delgado AG, Wilson KT, Peek RM, Correa P, Josenhans C, Fox JG, Suerbaum S. Different gastric microbiota compositions in two human populations with high and low gastric cancer risk in Colombia. Sci Rep. 2016; 6: 18594. PMID: 26729566, PMCID: PMC4700446, PII: srep18594, DOI: 10.1038/srep18594, ISSN: 2045-2322.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/26729566.
  • Waddell A, Vallance JE, Moore PD, Hummel AT, Wu D, Shanmukhappa SK, Fei L, Washington MK, Minar P, Coburn LA, Nakae S, Wilson KT, Denson LA, Hogan SP, Rosen MJ. IL-33 Signaling Protects from Murine Oxazolone Colitis by Supporting Intestinal Epithelial Function. Inflamm. Bowel Dis. 2015 Dec; 21(12): 2737-46. PMID: 26313694, PMCID: PMC4654638, DOI: 10.1097/MIB.0000000000000532, ISSN: 1536-4844.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/26313694.
  • Gogoi M, Datey A, Wilson KT, Chakravortty D. Dual role of arginine metabolism in establishing pathogenesis. Curr. Opin. Microbiol [print-electronic]. 2015 Nov 11/20/2015; 29: 43-8. PMID: 26610300, PII: S1369-5274(15)00153-8, DOI: 10.1016/j.mib.2015.10.005, ISSN: 1879-0364.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/26610300.
  • Schneider BG, Mera R, Piazuelo MB, Bravo JC, Zabaleta J, Delgado AG, Bravo LE, Wilson KT, El-Rifai W, Peek RM, Correa P. DNA Methylation Predicts Progression of Human Gastric Lesions. Cancer Epidemiol. Biomarkers Prev [print-electronic]. 2015 Oct; 24(10): 1607-13. PMID: 26269563, PMCID: PMC4592454, PII: 1055-9965.EPI-15-0388, DOI: 10.1158/1055-9965.EPI-15-0388, ISSN: 1538-7755.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/26269563.
  • Sharifnia T, Antoun J, Verriere TG, Suarez G, Wattacheril J, Wilson KT, Peek RM, Abumrad NN, Flynn CR. Hepatic TLR4 signaling in obese NAFLD. Am. J. Physiol. Gastrointest. Liver Physiol [print-electronic]. 2015 Aug 8/15/2015; 309(4): G270-8. PMID: 26113297, PMCID: PMC4537925, PII: ajpgi.00304.2014, DOI: 10.1152/ajpgi.00304.2014, ISSN: 1522-1547.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/26113297.
  • Barrett CW, Reddy VK, Short SP, Motley AK, Lintel MK, Bradley AM, Freeman T, Vallance J, Ning W, Parang B, Poindexter SV, Fingleton B, Chen X, Washington MK, Wilson KT, Shroyer NF, Hill KE, Burk RF, Williams CS. Selenoprotein P influences colitis-induced tumorigenesis by mediating stemness and oxidative damage. J. Clin. Invest [print-electronic]. 2015 Jul 7/1/2015; 125(7): 2646-60. PMID: 26053663, PMCID: PMC4563672, PII: 76099, DOI: 10.1172/JCI76099, ISSN: 1558-8238.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/26053663.
  • Chaturvedi R, de Sablet T, Asim M, Piazuelo MB, Barry DP, Verriere TG, Sierra JC, Hardbower DM, Delgado AG, Schneider BG, Israel DA, Romero-Gallo J, Nagy TA, Morgan DR, Murray-Stewart T, Bravo LE, Peek RM, Fox JG, Woster PM, Casero RA, Correa P, Wilson KT. Increased Helicobacter pylori-associated gastric cancer risk in the Andean region of Colombia is mediated by spermine oxidase. Oncogene [print-electronic]. 2015 Jun; 34(26): 3429-40. PMID: 25174398, PMCID: PMC4345146, PII: onc2014273, DOI: 10.1038/onc.2014.273, ISSN: 1476-5594.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/25174398.
  • Wroblewski LE, Piazuelo MB, Chaturvedi R, Schumacher M, Aihara E, Feng R, Noto JM, Delgado A, Israel DA, Zavros Y, Montrose MH, Shroyer N, Correa P, Wilson KT, Peek RM. Helicobacter pylori targets cancer-associated apical-junctional constituents in gastroids and gastric epithelial cells. Gut [print-electronic]. 2015 May; 64(5): 720-30. PMID: 25123931, PMCID: PMC4329117, PII: gutjnl-2014-307650, DOI: 10.1136/gutjnl-2014-307650, ISSN: 1468-3288.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/25123931.
  • Krakowiak MS, Noto JM, Piazuelo MB, Hardbower DM, Romero-Gallo J, Delgado A, Chaturvedi R, Correa P, Wilson KT, Peek RM. Matrix metalloproteinase 7 restrains Helicobacter pylori-induced gastric inflammation and premalignant lesions in the stomach by altering macrophage polarization. Oncogene [print-electronic]. 2015 Apr 4/2/2015; 34(14): 1865-71. PMID: 24837365, PMCID: PMC4237684, PII: onc2014135, DOI: 10.1038/onc.2014.135, ISSN: 1476-5594.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/24837365.
  • Poindexter SV, Reddy VK, Mittal MK, Williams AM, Washington MK, Harris E, Mah A, Hiebert SW, Singh K, Chaturvedi R, Wilson KT, Lund PK, Williams CS. Transcriptional corepressor MTG16 regulates small intestinal crypt proliferation and crypt regeneration after radiation-induced injury. Am. J. Physiol. Gastrointest. Liver Physiol [print-electronic]. 2015 Mar 3/15/2015; 308(6): G562-71. PMID: 25573176, PMCID: PMC4360050, PII: ajpgi.00253.2014, DOI: 10.1152/ajpgi.00253.2014, ISSN: 1522-1547.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/25573176.
  • Asim M, Chikara SK, Ghosh A, Vudathala S, Romero-Gallo J, Krishna US, Wilson KT, Israel DA, Peek RM, Chaturvedi R. Draft Genome Sequence of Gerbil-Adapted Carcinogenic Helicobacter pylori Strain 7.13. Genome Announc. 2015; 3(3): PMID: 26067974, PMCID: PMC4463538, PII: 3/3/e00641-15, DOI: 10.1128/genomeA.00641-15, ISSN: 2169-8287.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/26067974.
  • Ahmad R, Chaturvedi R, Olivares-Villagómez D, Habib T, Asim M, Shivesh P, Polk DB, Wilson KT, Washington MK, Van Kaer L, Dhawan P, Singh AB. Targeted colonic claudin-2 expression renders resistance to epithelial injury, induces immune suppression, and protects from colitis. Mucosal Immunol [print-electronic]. 2014 Nov; 7(6): 1340-53. PMID: 24670427, PMCID: PMC4221190, PII: mi201421, DOI: 10.1038/mi.2014.21, ISSN: 1935-3456.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/24670427.
  • Van Kaer L, Algood HM, Singh K, Parekh VV, Greer MJ, Piazuelo MB, Weitkamp JH, Matta P, Chaturvedi R, Wilson KT, Olivares-Villagómez D. CD8aa¿ innate-type lymphocytes in the intestinal epithelium mediate mucosal immunity. Immunity [print-electronic]. 2014 Sep 9/18/2014; 41(3): 451-64. PMID: 25220211, PMCID: PMC4169715, PII: S1074-7613(14)00304-5, DOI: 10.1016/j.immuni.2014.08.010, ISSN: 1097-4180.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/25220211.
  • 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.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/25108023.
  • Hardbower DM, Peek RM, Wilson KT. At the Bench: Helicobacter pylori, dysregulated host responses, DNA damage, and gastric cancer. J. Leukoc. Biol [print-electronic]. 2014 Aug; 96(2): 201-12. PMID: 24868089, PMCID: PMC4101087, PII: jlb.4BT0214-099R, DOI: 10.1189/jlb.4BT0214-099R, ISSN: 1938-3673.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/24868089.
  • Chaturvedi R, Asim M, Piazuelo MB, Yan F, Barry DP, Sierra JC, Delgado AG, Hill S, Casero RA, Bravo LE, Dominguez RL, Correa P, Polk DB, Washington MK, Rose KL, Schey KL, Morgan DR, Peek RM, Wilson KT. Activation of EGFR and ERBB2 by Helicobacter pylori results in survival of gastric epithelial cells with DNA damage. Gastroenterology [print-electronic]. 2014 Jun; 146(7): 1739-51.e14. PMID: 24530706, PMCID: PMC4035375, PII: S0016-5085(14)00192-9, DOI: 10.1053/j.gastro.2014.02.005, ISSN: 1528-0012.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/24530706.
  • Wang D, Fu L, Ning W, Guo L, Sun X, Dey SK, Chaturvedi R, Wilson KT, DuBois RN. Peroxisome proliferator-activated receptor d promotes colonic inflammation and tumor growth. Proc. Natl. Acad. Sci. U.S.A [print-electronic]. 2014 May 5/13/2014; 111(19): 7084-9. PMID: 24763687, PMCID: PMC4024916, PII: 1324233111, DOI: 10.1073/pnas.1324233111, ISSN: 1091-6490.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/24763687.
  • Shi C, Washington MK, Chaturvedi R, Drosos Y, Revetta FL, Weaver CJ, Buzhardt E, Yull FE, Blackwell TS, Sosa-Pineda B, Whitehead RH, Beauchamp RD, Wilson KT, Means AL. Fibrogenesis in pancreatic cancer is a dynamic process regulated by macrophage-stellate cell interaction. Lab. Invest [print-electronic]. 2014 Apr; 94(4): 409-21. PMID: 24535260, PMCID: PMC3992484, PII: labinvest201410, DOI: 10.1038/labinvest.2014.10, ISSN: 1530-0307.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/24535260.
  • Chaturvedi R, Asim M, Barry DP, Frye JW, Casero RA, Wilson KT. Spermine oxidase is a regulator of macrophage host response to Helicobacter pylori: enhancement of antimicrobial nitric oxide generation by depletion of spermine. Amino Acids [print-electronic]. 2014 Mar; 46(3): 531-42. PMID: 23820617, PMCID: PMC3812355, DOI: 10.1007/s00726-013-1531-z, ISSN: 1438-2199.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/23820617.
  • Lu N, Wang L, Cao H, Liu L, Van Kaer L, Washington MK, Rosen MJ, Dubé PE, Wilson KT, Ren X, Hao X, Polk DB, Yan F. Activation of the epidermal growth factor receptor in macrophages regulates cytokine production and experimental colitis. J. Immunol [print-electronic]. 2014 Feb 2/1/2014; 192(3): 1013-23. PMID: 24391216, PMCID: PMC4006992, PII: jimmunol.1300133, DOI: 10.4049/jimmunol.1300133, ISSN: 1550-6606.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/24391216.
  • Falaiye TO, Mitchell KR, Lu Z, Saville BR, Horst SN, Moulton DE, Schwartz DA, Wilson KT, Rosen MJ. Outcomes following infliximab therapy for pediatric patients hospitalized with refractory colitis-predominant IBD. J. Pediatr. Gastroenterol. Nutr. 2014 Feb; 58(2): 213-9. PMID: 24048170, PMCID: PMC3946904, DOI: 10.1097/MPG.0b013e3182a98df2, ISSN: 1536-4801.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/24048170.
  • Kodaman N, Pazos A, Schneider BG, Piazuelo MB, Mera R, Sobota RS, Sicinschi LA, Shaffer CL, Romero-Gallo J, de Sablet T, Harder RH, Bravo LE, Peek RM, Wilson KT, Cover TL, Williams SM, Correa P. Human and Helicobacter pylori coevolution shapes the risk of gastric disease. Proc. Natl. Acad. Sci. U.S.A [print-electronic]. 2014 Jan 1/28/2014; 111(4): 1455-60. PMID: 24474772, PMCID: PMC3910595, PII: 1318093111, DOI: 10.1073/pnas.1318093111, ISSN: 1091-6490.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/24474772.
  • Carbo A, Olivares-Villagómez D, Hontecillas R, Bassaganya-Riera J, Chaturvedi R, Piazuelo MB, Delgado A, Washington MK, Wilson KT, Algood HM. Systems modeling of the role of interleukin-21 in the maintenance of effector CD4+ T cell responses during chronic Helicobacter pylori infection. MBio. 2014; 5(4): e01243-14. PMID: 25053783, PMCID: PMC4120195, PII: mBio.01243-14, DOI: 10.1128/mBio.01243-14, ISSN: 2150-7511.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/25053783.
  • Noto JM, Piazuelo MB, Chaturvedi R, Bartel CA, Thatcher EJ, Delgado A, Romero-Gallo J, Wilson KT, Correa P, Patton JG, Peek RM. Strain-specific suppression of microRNA-320 by carcinogenic Helicobacter pylori promotes expression of the antiapoptotic protein Mcl-1. Am. J. Physiol. Gastrointest. Liver Physiol [print-electronic]. 2013 Dec; 305(11): G786-96. PMID: 24136787, PMCID: PMC3882435, PII: ajpgi.00279.2013, DOI: 10.1152/ajpgi.00279.2013, ISSN: 1522-1547.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/24136787.
  • Hardbower DM, de Sablet T, Chaturvedi R, Wilson KT. Chronic inflammation and oxidative stress: the smoking gun for Helicobacter pylori-induced gastric cancer?. Gut Microbes [print-electronic]. 2013 Nov; 4(6): 475-81. PMID: 23811829, PMCID: PMC3928159, PII: 25583, DOI: 10.4161/gmic.25583, ISSN: 1949-0984.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/23811829.
  • Schneider BG, Piazuelo MB, Sicinschi LA, Mera R, Peng DF, Roa JC, Romero-Gallo J, Delgado AG, de Sablet T, Bravo LE, Wilson KT, El-Rifai W, Peek RM, Correa P. Virulence of infecting Helicobacter pylori strains and intensity of mononuclear cell infiltration are associated with levels of DNA hypermethylation in gastric mucosae. Epigenetics [print-electronic]. 2013 Nov; 8(11): 1153-61. PMID: 24128875, PMCID: PMC3927747, PII: 26072, DOI: 10.4161/epi.26072, ISSN: 1559-2308.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/24128875.
  • Williams CS, Bradley AM, Chaturvedi R, Singh K, Piazuelo MB, Chen X, McDonough EM, Schwartz DA, Brown CT, Allaman MM, Coburn LA, Horst SN, Beaulieu DB, Choksi YA, Washington MK, Williams AD, Fisher MA, Zinkel SS, Peek RM, Wilson KT, Hiebert SW. MTG16 contributes to colonic epithelial integrity in experimental colitis. Gut [print-electronic]. 2013 Oct; 62(10): 1446-55. PMID: 22833394, PMCID: PMC3663894, PII: gutjnl-2011-301439, DOI: 10.1136/gutjnl-2011-301439, ISSN: 1468-3288.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/22833394.
  • Singh K, Coburn LA, Barry DP, Asim M, Scull BP, Allaman MM, Lewis ND, Washington MK, Rosen MJ, Williams CS, Chaturvedi R, Wilson KT. Deletion of cationic amino acid transporter 2 exacerbates dextran sulfate sodium colitis and leads to an IL-17-predominant T cell response. Am. J. Physiol. Gastrointest. Liver Physiol [print-electronic]. 2013 Aug 8/1/2013; 305(3): G225-40. PMID: 23703655, PMCID: PMC3742860, PII: ajpgi.00091.2013, DOI: 10.1152/ajpgi.00091.2013, ISSN: 1522-1547.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/23703655.
  • Sierra JC, Hobbs S, Chaturvedi R, Yan F, Wilson KT, Peek RM, Polk DB. Induction of COX-2 expression by Helicobacter pylori is mediated by activation of epidermal growth factor receptor in gastric epithelial cells. Am. J. Physiol. Gastrointest. Liver Physiol [print-electronic]. 2013 Jul 7/15/2013; 305(2): G196-203. PMID: 23681474, PMCID: PMC3725681, PII: ajpgi.00495.2012, DOI: 10.1152/ajpgi.00495.2012, ISSN: 1522-1547.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/23681474.
  • Sheh A, Chaturvedi R, Merrell DS, Correa P, Wilson KT, Fox JG. Phylogeographic origin of Helicobacter pylori determines host-adaptive responses upon coculture with gastric epithelial cells. Infect. Immun [print-electronic]. 2013 Jul; 81(7): 2468-77. PMID: 23630959, PMCID: PMC3697613, PII: IAI.01182-12, DOI: 10.1128/IAI.01182-12, ISSN: 1098-5522.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/23630959.
  • Parekh VV, Wu L, Olivares-Villagómez D, Wilson KT, Van Kaer L. Activated invariant NKT cells control central nervous system autoimmunity in a mechanism that involves myeloid-derived suppressor cells. J. Immunol [print-electronic]. 2013 Mar 3/1/2013; 190(5): 1948-60. PMID: 23345328, PMCID: PMC3577977, PII: jimmunol.1201718, DOI: 10.4049/jimmunol.1201718, ISSN: 1550-6606.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/23345328.
  • Rosen MJ, Chaturvedi R, Washington MK, Kuhnhein LA, Moore PD, Coggeshall SS, McDonough EM, Weitkamp JH, Singh AB, Coburn LA, Williams CS, Yan F, Van Kaer L, Peebles RS, Wilson KT. STAT6 deficiency ameliorates severity of oxazolone colitis by decreasing expression of claudin-2 and Th2-inducing cytokines. J. Immunol [print-electronic]. 2013 Feb 2/15/2013; 190(4): 1849-58. PMID: 23303670, PMCID: PMC3563924, PII: jimmunol.1201373, DOI: 10.4049/jimmunol.1201373, ISSN: 1550-6606.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/23303670.
  • Barrett CW, Ning W, Chen X, Smith JJ, Washington MK, Hill KE, Coburn LA, Peek RM, Chaturvedi R, Wilson KT, Burk RF, Williams CS. Tumor suppressor function of the plasma glutathione peroxidase gpx3 in colitis-associated carcinoma. Cancer Res [print-electronic]. 2013 Feb 2/1/2013; 73(3): 1245-55. PMID: 23221387, PMCID: PMC3563732, PII: 0008-5472.CAN-12-3150, DOI: 10.1158/0008-5472.CAN-12-3150, ISSN: 1538-7445.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/23221387.
  • 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.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/23051580.
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  • Cross RK, Wilson KT, Binion DG. Narcotic use in patients with Crohn's disease. Am. J. Gastroenterol. 2005 Oct; 100(10): 2225-9. PMID: 16181373, PII: AJG256, DOI: 10.1111/j.1572-0241.2005.00256.x, ISSN: 0002-9270.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/16181373.
  • Cheng Y, Chaturvedi R, Asim M, Bussière FI, Scholz A, Xu H, Casero RA, Wilson KT. Helicobacter pylori-induced macrophage apoptosis requires activation of ornithine decarboxylase by c-Myc. J. Biol. Chem [print-electronic]. 2005 Jun 6/10/2005; 280(23): 22492-6. PMID: 15843384, PII: C500122200, DOI: 10.1074/jbc.C500122200, ISSN: 0021-9258.
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  • Cross RK, Wilson KT, Binion DG. Polypharmacy and Crohn's disease. Aliment. Pharmacol. Ther. 2005 May 5/15/2005; 21(10): 1211-6. PMID: 15882241, PII: APT2429, DOI: 10.1111/j.1365-2036.2005.02429.x, ISSN: 0269-2813.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/15882241.
  • 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.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/15995584.
  • 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.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/15548540.
  • Xu H, Chaturvedi R, Cheng Y, Bussiere FI, Asim M, Yao MD, Potosky D, Meltzer SJ, Rhee JG, Kim SS, Moss SF, Hacker A, Wang Y, Casero RA, Wilson KT. Spermine oxidation induced by Helicobacter pylori results in apoptosis and DNA damage: implications for gastric carcinogenesis. Cancer Res. 2004 Dec 12/1/2004; 64(23): 8521-5. PMID: 15574757, PII: 64/23/8521, DOI: 10.1158/0008-5472.CAN-04-3511, ISSN: 0008-5472.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/15574757.
  • 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.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/15247269.
  • 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.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/15265947.
  • 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.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/15128819.
  • Ma X, Yang Q, Wilson KT, Kundu N, Meltzer SJ, Fulton AM. Promoter methylation regulates cyclooxygenase expression in breast cancer. Breast Cancer Res [print-electronic]. 2004; 6(4): R316-21. PMID: 15217498, PMCID: PMC468630, PII: bcr793, DOI: 10.1186/bcr793, ISSN: 1465-542X.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/15217498.
  • 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.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/14530307.
  • Cross RK, Wilson KT. Nitric oxide in inflammatory bowel disease. Inflamm. Bowel Dis. 2003 May; 9(3): 179-89. PMID: 12792224, ISSN: 1078-0998.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/12792224.
  • Panchal PC, Forman JS, Blumberg DR, Wilson KT. Helicobacter pylori infection: pathogenesis. Curr. Opin. Gastroenterol. 2003 Jan; 19(1): 4-10. PMID: 15699887, PII: 00001574-200301000-00002, ISSN: 0267-1379.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/15699887.
  • Rafiee P, Johnson CP, Li MS, Ogawa H, Heidemann J, Fisher PJ, Lamirand TH, Otterson MF, Wilson KT, Binion DG. Cyclosporine A enhances leukocyte binding by human intestinal microvascular endothelial cells through inhibition of p38 MAPK and iNOS. Paradoxical proinflammatory effect on the microvascular endothelium. J. Biol. Chem [print-electronic]. 2002 Sep 9/20/2002; 277(38): 35605-15. PMID: 12110686, PII: M205826200, DOI: 10.1074/jbc.M205826200, ISSN: 0021-9258.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/12110686.
  • 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.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/12055207.
  • 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.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/11971019.
  • Wilson KT. Angiogenic markers, neovascularization and malignant deformation of Barrett's esophagus. Dis. Esophagus. 2002; 15(1): 16-21. PMID: 12060038, PII: 212, ISSN: 1120-8694.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/12060038.
  • 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.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/11717441.
  • Akhtar M, Cheng Y, Magno RM, Ashktorab H, Smoot DT, Meltzer SJ, Wilson KT. Promoter methylation regulates Helicobacter pylori-stimulated cyclooxygenase-2 expression in gastric epithelial cells. Cancer Res. 2001 Mar 3/15/2001; 61(6): 2399-403. PMID: 11289104, ISSN: 0008-5472.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/11289104.
  • Fleisher AS, Esteller M, Tamura G, Rashid A, Stine OC, Yin J, Zou TT, Abraham JM, Kong D, Nishizuka S, James SP, Wilson KT, Herman JG, Meltzer SJ. Hypermethylation of the hMLH1 gene promoter is associated with microsatellite instability in early human gastric neoplasia. Oncogene. 2001 Jan 1/18/2001; 20(3): 329-35. PMID: 11313962, DOI: 10.1038/sj.onc.1204104, ISSN: 0950-9232.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/11313962.
  • Binion DG, Rafiee P, Ramanujam KS, Fu S, Fisher PJ, Rivera MT, Johnson CP, Otterson MF, Telford GL, Wilson KT. Deficient iNOS in inflammatory bowel disease intestinal microvascular endothelial cells results in increased leukocyte adhesion. Free Radic. Biol. Med. 2000 Nov 11/1/2000; 29(9): 881-8. PMID: 11063913, PII: S0891-5849(00)00391-9, ISSN: 0891-5849.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/11063913.
  • Meyer F, Wilson KT, James SP. Modulation of innate cytokine responses by products of Helicobacter pylori. Infect. Immun. 2000 Nov; 68(11): 6265-72. PMID: 11035734, PMCID: PMC97708, ISSN: 0019-9567.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/11035734.
  • Fleisher AS, Esteller M, Harpaz N, Leytin A, Rashid A, Xu Y, Liang J, Stine OC, Yin J, Zou TT, Abraham JM, Kong D, Wilson KT, James SP, Herman JG, Meltzer SJ. Microsatellite instability in inflammatory bowel disease-associated neoplastic lesions is associated with hypermethylation and diminished expression of the DNA mismatch repair gene, hMLH1. Cancer Res. 2000 Sep 9/1/2000; 60(17): 4864-8. PMID: 10987299, ISSN: 0008-5472.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/10987299.
  • Tsuchiya T, Tamura G, Sato K, Endoh Y, Sakata K, Jin Z, Motoyama T, Usuba O, Kimura W, Nishizuka S, Wilson KT, James SP, Yin J, Fleisher AS, Zou T, Silverberg SG, Kong D, Meltzer SJ. Distinct methylation patterns of two APC gene promoters in normal and cancerous gastric epithelia. Oncogene. 2000 Jul 7/27/2000; 19(32): 3642-6. PMID: 10951570, DOI: 10.1038/sj.onc.1203704, ISSN: 0950-9232.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/10951570.
  • Tamura G, Yin J, Wang S, Fleisher AS, Zou T, Abraham JM, Kong D, Smolinski KN, Wilson KT, James SP, Silverberg SG, Nishizuka S, Terashima M, Motoyama T, Meltzer SJ. E-Cadherin gene promoter hypermethylation in primary human gastric carcinomas. J. Natl. Cancer Inst. 2000 Apr 4/5/2000; 92(7): 569-73. PMID: 10749913, ISSN: 0027-8874.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/10749913.
  • Malamud A, Wilson KT. Treatment of gastrointestinal infections. Curr. Opin. Gastroenterol. 2000 Jan; 16(1): 51-5. PMID: 17024016, PII: 00001574-200001000-00009, ISSN: 0267-1379.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/17024016.
  • Fu S, Ramanujam KS, Wong A, Fantry GT, Drachenberg CB, James SP, Meltzer SJ, Wilson KT. Increased expression and cellular localization of inducible nitric oxide synthase and cyclooxygenase 2 in Helicobacter pylori gastritis. Gastroenterology. 1999 Jun; 116(6): 1319-29. PMID: 10348815, PII: S0016508599005442, ISSN: 0016-5085.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/10348815.
  • Fleisher AS, Esteller M, Wang S, Tamura G, Suzuki H, Yin J, Zou TT, Abraham JM, Kong D, Smolinski KN, Shi YQ, Rhyu MG, Powell SM, James SP, Wilson KT, Herman JG, Meltzer SJ. Hypermethylation of the hMLH1 gene promoter in human gastric cancers with microsatellite instability. Cancer Res. 1999 Mar 3/1/1999; 59(5): 1090-5. PMID: 10070967, ISSN: 0008-5472.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/10070967.
  • Wilson KT, Fantry GT. Pathogenesis of Helicobacter pylori infection. Curr. Opin. Gastroenterol. 1999 Jan; 15(1): 66-71. PMID: 17023920, PII: 00001574-199901000-00012, ISSN: 0267-1379.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/17023920.
  • Binion DG, Fu S, Ramanujam KS, Chai YC, Dweik RA, Drazba JA, Wade JG, Ziats NP, Erzurum SC, Wilson KT. INOS expression in human intestinal microvascular endothelial cells inhibits leukocyte adhesion. Am. J. Physiol. 1998 Sep; 275(3 Pt 1): G592-603. PMID: 9724273, ISSN: 0002-9513.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/9724273.
  • Varanasi RV, Fantry GT, Wilson KT. Decreased prevalence of Helicobacter pylori infection in gastroesophageal reflux disease. Helicobacter. 1998 Sep; 3(3): 188-94. PMID: 9731990, ISSN: 1083-4389.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/9731990.
  • Wilson KT, Fu S, Ramanujam KS, Meltzer SJ. Increased expression of inducible nitric oxide synthase and cyclooxygenase-2 in Barrett's esophagus and associated adenocarcinomas. Cancer Res. 1998 Jul 7/15/1998; 58(14): 2929-34. PMID: 9679948, ISSN: 0008-5472.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/9679948.
  • Kundu N, Dorsey R, Jackson MJ, Guiterrez P, Wilson K, Fu S, Ramanujam K, Thomas E, Fulton AM. Interleukin-10 gene transfer inhibits murine mammary tumors and elevates nitric oxide. Int. J. Cancer. 1998 May 5/29/1998; 76(5): 713-9. PMID: 9610731, PII: 10.1002/(SICI)1097-0215(19980529)76:5<713::AID-IJC17>3.0.CO;2-4, ISSN: 0020-7136.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/9610731.
  • Wilson KT, Ramanujam KS, Mobley HL, Musselman RF, James SP, Meltzer SJ. Helicobacter pylori stimulates inducible nitric oxide synthase expression and activity in a murine macrophage cell line. Gastroenterology. 1996 Dec; 111(6): 1524-33. PMID: 8942731, PII: S0016-5085(96)70014-8, ISSN: 0016-5085.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/8942731.
  • Wilson KT, Vaandrager AB, De Vente J, Musch MW, De Jonge HR, Chang EB. Production and localization of cGMP and PGE2 in nitroprusside-stimulated rat colonic ion transport. Am. J. Physiol. 1996 Mar; 270(3 Pt 1): C832-40. PMID: 8638664, ISSN: 0002-9513.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/8638664.
  • Wilson, KT, Chang, EB. Immune regulation of intestinal secretion. Practical Gastroenterol. 1994; 3: 22J-22Q.
  • Wilson KT, Xie Y, Musch MW, Chang EB. Sodium nitroprusside stimulates anion secretion and inhibits sodium chloride absorption in rat colon. J. Pharmacol. Exp. Ther. 1993 Jul; 266(1): 224-30. PMID: 8331560, ISSN: 0022-3565.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/8331560.
  • Wilson, KT, Musch, MW, Chang, EB. In MacDermott, R, Stenson, W, eds., Inflammatory Bowel Disease. New York: Elsevier. [place unknown: publisher unknown]; 1992.