Vanderbilt-Ingram Cancer Center

The VICC.ORG Investigator Directory

Timothy L. Cover, M.D.

Professor of Medicine
VICC Member
Researcher

Contact Information:

Vanderbilt University Medical Center
A-3310 Medical Center North
Nashville, TN 37232-2605
615-322-2035

Research Specialty:

Bacteria-host interactions, bacterial toxins, Helicobacter pylori, gastric cancer

Research Description:

Research projects in the Cover laboratory are focused on investigating molecular mechanisms by which pathogenic bacteria cause disease in humans. We are particularly interested in the bacterium Helicobacter pylori, which contributes to the development of stomach cancer and peptic ulcer disease. H. pylori persistently colonizes the acidic gastric mucosa of humans, and persistent H. pylori colonization of the stomach results in chronic gastric inflammation. H. pylori is the only bacterial pathogen that commonly causes cancer in humans, and stomach cancer is the second leading cause of cancer mortality worldwide.

To investigate molecular mechanisms by which H. pylori causes disease, our laboratory uses a variety of molecular biology, cell biology, genomic, and immunologic methods. Current projects include (i) investigation of two H. pylori toxins (VacA and CagA) in cell culture and animal models, (ii) investigation of the H. pylori type IV secretion system that delivers CagA into gastric epithelial cells, (iii) investigation of mechanisms by which gene expression is regulated in H. pylori, and (iv) comparative genome sequence analysis of H. pylori strains isolated from patients with different disease states, with the goal of identifying new bacterial biomarkers that predict the development of gastric cancer.

Publications:

• Duncan, SS, Valk, PL, McClain, MS, Shaffer, CL, Metcalf, JA, Bordenstein, SR, Cover, TL Comparative Genomic Analysis of East Asian and Non-Asian Helicobacter pylori Strains Identifies Rapidly Evolving Genes. PLoS One, 8(1), e55120, 2013.
• Serrano, C, Wright, SW, Bimczok, D, Shaffer, CL, Cover, TL, Venegas, A, Salazar, MG, Smythies, LE, Harris, PR, Smith, PD Downregulated Th17 responses are associated with reduced gastritis in Helicobacter pylori-infected children. Mucosal Immunol, 2013.
• Radin, JN, Gaddy, JA, Gonz¿¿lez-Rivera, C, Loh, JT, Algood, HM, Cover, TL Flagellar Localization of a Helicobacter pylori Autotransporter Protein. MBio, 4(2), 2013.
• Barrozo, RM, Cooke, CL, Hansen, LM, Lam, AM, Gaddy, JA, Johnson, EM, Cariaga, TA, Suarez, G, Peek, RM, Cover, TL, Solnick, JV Functional Plasticity in the Type IV Secretion System of Helicobacter pylori. PLoS Pathog, 9(2), e1003189, 2013.
• Gaddy, JA, Radin, JN, Loh, JT, Zhang, F, Washington, MK, Peek, RM, Algood, HM, Cover, TL High dietary salt intake exacerbates Helicobacter pylori-induced gastric carcinogenesis. Infect Immun, 2013.
• Noto, JM, Gaddy, JA, Lee, JY, Piazuelo, MB, Friedman, DB, Colvin, DC, Romero-Gallo, J, Suarez, G, Loh, J, Slaughter, JC, Tan, S, Morgan, DR, Wilson, KT, Bravo, LE, Correa, P, Cover, TL, Amieva, MR, Peek, RM Iron deficiency accelerates Helicobacter pylori-induced carcinogenesis in rodents and humans. J Clin Invest, 123(1), 479-92, 2013.
• Chambers, MG, Pyburn, TM, Gonz¿¿lez-Rivera, C, Collier, SE, Eli, I, Yip, CK, Takizawa, Y, Lacy, DB, Cover, TL, Ohi, MD Structural Analysis of the Oligomeric States of Helicobacter pylori VacA Toxin. J Mol Biol, 425(3), 524-35, 2013.
• Johnson, EM, Gaddy, JA, Cover, TL Alterations in Helicobacter pylori Triggered by Contact with Gastric Epithelial Cells. Front Cell Infect Microbiol, 217, 2012.
• Conradi, J, Tegtmeyer, N, Wo¿¿na, M, Wissbrock, M, Michalek, C, Gagell, C, Cover, TL, Frank, R, Sewald, N, Backert, S An RGD Helper Sequence in CagL of Helicobacter pylori Assists in Interactions with Integrins and Injection of CagA. Front Cell Infect Microbiol, 270, 2012.
• Loh, JT, Friedman, DB, Piazuelo, MB, Bravo, LE, Wilson, KT, Peek, RM, Correa, P, Cover, TL Analysis of Helicobacter pylori cagA promoter elements required for salt-induced upregulation of CagA expression. Infect Immun, 80(9), 3094-106, 2012.
• Duncan, SS, Valk, PL, Shaffer, CL, Bordenstein, SR, Cover, TL J-Western forms of Helicobacter pylori cagA constitute a distinct phylogenetic group with a widespread geographic distribution. J Bacteriol, 194(6), 1593-604, 2012.
• Cover, TL Perspectives on methodology for in vitro culture of Helicobacter pylori. Methods Mol Biol, 92111-5, 2012.
• Cover, TL Role of Helicobacter pylori CagL in modulating gastrin expression. Gut, 61(7), 965-6, 2012.
• González-Rivera, C, Algood, HM, Radin, JN, McClain, MS, Cover, TL The Intermediate Region of Helicobacter pylori VacA Is a Determinant of Toxin Potency in a Jurkat T Cell Assay. Infect Immun, 80(8), 2578-88, 2012.
• Loh, JT, Shaffer, CL, Piazuelo, MB, Bravo, LE, McClain, MS, Correa, P, Cover, TL Analysis of cagA in Helicobacter pylori Strains from Colombian Populations with Contrasting Gastric Cancer Risk Reveals a Biomarker for Disease Severity. Cancer Epidemiol Biomarkers Prev, 20(10), 2237-49, 2011.
• Yan, F, Cao, H, Cover, TL, Washington, MK, Shi, Y, Liu, L, Chaturvedi, R, Peek, RM, Wilson, KT, Polk, DB Colon-specific delivery of a probiotic-derived soluble protein ameliorates intestinal inflammation in mice through an EGFR-dependent mechanism. J Clin Invest, 121(6), 2242-53, 2011.
• Radin, JN, González-Rivera, C, Ivie, SE, McClain, MS, Cover, TL Helicobacter pylori VacA Induces Programmed Necrosis in Gastric Epithelial Cells. Infect Immun, 79(7), 2535-43, 2011.
• Shaffer, CL, Gaddy, JA, Loh, JT, Johnson, EM, Hill, S, Hennig, EE, McClain, MS, McDonald, WH, Cover, TL Helicobacter pylori exploits a unique repertoire of type IV secretion system components for pilus assembly at the bacteria-host cell interface. PLoS Pathog, 7(9), e1002237, 2011.
• de Sablet, T, Piazuelo, MB, Shaffer, CL, Schneider, BG, Asim, M, Chaturvedi, R, Bravo, LE, Sicinschi, LA, Delgado, AG, Mera, RM, Israel, DA, Romero-Gallo, J, Peek, RM, Cover, TL, Correa, P, Wilson, KT Phylogeographic origin of Helicobacter pylori is a determinant of gastric cancer risk. Gut, 60(9), 1189-95, 2011.
• Nagy, TA, Wroblewski, LE, Wang, D, Piazuelo, MB, Delgado, A, Romero-Gallo, J, Noto, J, Israel, DA, Ogden, SR, Correa, P, Cover, TL, Peek, RM β-Catenin and p120 mediate PPARδ-dependent proliferation induced by Helicobacter pylori in human and rodent epithelia. Gastroenterology, 141(2), 553-64, 2011.
• Ivie, SE, McClain, MS, Algood, HM, Lacy, DB, Cover, TL Analysis of a beta-helical region in the p55 domain of Helicobacter pylori vacuolating toxin. BMC Microbiol, 1060, 2010.
• Loh, JT, Gupta, SS, Friedman, DB, Krezel, AM, Cover, TL Analysis of protein expression regulated by the Helicobacter pylori ArsRS two-component signal transduction system. J Bacteriol, 192(8), 2034-43, 2010.
• Shen, F, Hobley, L, Doherty, N, Loh, JT, Cover, TL, Sockett, RE, Hardie, KR, Atherton, JC In Helicobacter pylori auto-inducer-2, but not LuxS/MccAB catalysed reverse transsulphuration, regulates motility through modulation of flagellar gene transcription. BMC Microbiol, 10210, 2010.
• Gangwer, KA, Shaffer, CL, Suerbaum, S, Lacy, DB, Cover, TL, Bordenstein, SR Molecular evolution of the Helicobacter pylori vacuolating toxin gene vacA. J Bacteriol, 192(23), 6126-35, 2010.
• González-Rivera, C, Gangwer, KA, McClain, MS, Eli, IM, Chambers, MG, Ohi, MD, Lacy, DB, Cover, TL Reconstitution of Helicobacter pylori VacA toxin from purified components. Biochemistry, 49(27), 5743-52, 2010.
• Yan, F, Cao, H, Chaturvedi, R, Krishna, U, Hobbs, SS, Dempsey, PJ, Peek, RM, Cover, TL, Washington, MK, Wilson, KT, Polk, DB Epidermal growth factor receptor activation protects gastric epithelial cells from Helicobacter pylori-induced apoptosis. Gastroenterology, 136(4), 1297-1307, 2009.
• McClain, MS, Shaffer, CL, Israel, DA, Peek, RM, Cover, TL Genome sequence analysis of Helicobacter pylori strains associated with gastric ulceration and gastric cancer. BMC Genomics, 10(1), 3, 2009.
• Cover, TL, Blaser, MJ Helicobacter pylori in health and disease. Gastroenterology, 136(6), 1863-73, 2009.
• Algood, HM, Allen, SS, Washington, MK, Peek, RM, Miller, GG, Cover, TL Regulation of gastric B cell recruitment is dependent on IL-17 receptor A signaling in a model of chronic bacterial infection. J Immunol, 183(9), 5837-46, 2009.
• Gupta, SS, Borin, BN, Cover, TL, Krezel, AM Structural analysis of the DNA-binding domain of the Helicobacter pylori response regulator ArsR. J Biol Chem, 284(10), 6536-45, 2009.
• Cover, TL Beta2 integrin mediates entry of a bacterial toxin into T lymphocytes. Cell Host Microbe, 3(1), 5-6, 2008.
• Loh, JT, Torres, VJ, Algood, HM, McClain, MS, Cover, TL Helicobacter pylori HopQ outer membrane protein attenuates bacterial adherence to gastric epithelial cells. FEMS Microbiol Lett, 289(1), 53-8, 2008.
• Wang, F, Xia, P, Wu, F, Wang, D, Wang, W, Ward, T, Liu, Y, Aikhionbare, F, Guo, Z, Powell, M, Liu, B, Bi, F, Shaw, A, Zhu, Z, Elmoselhi, A, Fan, D, Cover, TL, Ding, X, Yao, X Helicobacter pylori VacA disrupts apical membrane-cytoskeletal interactions in gastric parietal cells. J Biol Chem, 283(39), 26714-25, 2008.
• Ivie, SE, McClain, MS, Torres, VJ, Algood, HM, Lacy, DB, Yang, R, Blanke, SR, Cover, TL Helicobacter pylori VacA subdomain required for intracellular toxin activity and assembly of functional oligomeric complexes. Infect Immun, 76(7), 2843-51, 2008.
• Ding, SZ, Olekhnovich, IN, Cover, TL, Peek, RM, Smith, MF, Goldberg, JB Helicobacter pylori and mitogen-activated protein kinases mediate activator protein-1 (AP-1) subcomponent protein expression and DNA-binding activity in gastric epithelial cells. FEMS Immunol Med Microbiol, 53(3), 385-94, 2008.
• Gangwer, KA, Mushrush, DJ, Stauff, DL, Spiller, B, McClain, MS, Cover, TL, Lacy, DB Crystal structure of the Helicobacter pylori vacuolating toxin p55 domain. Proc Natl Acad Sci U S A, 104(41), 16293-8, 2007.
• McClain, MS, Cover, TL Functional analysis of neutralizing antibodies against Clostridium perfringens epsilon-toxin. Infect Immun, 75(4), 1785-93, 2007.
• Torres, VJ, Vancompernolle, SE, Sundrud, MS, Unutmaz, D, Cover, TL Helicobacter pylori Vacuolating Cytotoxin Inhibits Activation-Induced Proliferation of Human T and B Lymphocyte Subsets. J Immunol, 179(8), 5433-40, 2007.
• Scott Algood, HM, Gallo-Romero, J, Wilson, KT, Peek, RM, Cover, TL Host response to Helicobacter pylori infection before initiation of the adaptive immune response. FEMS Immunol Med Microbiol, 51577-586, 2007.
• Chaturvedi, R, Asim, M, Lewis, ND, Algood, HM, Cover, TL, Kim, PY, Wilson, KT L-Arginine Availability Regulates Inducible Nitric Oxide Synthase-Dependent Host Defense against Helicobacter pylori. Infect Immun, 75(9), 4305-15, 2007.
• Loh, JT, Torres, VJ, Cover, TL Regulation of Helicobacter pylori cagA expression in response to salt. Cancer Res, 67(10), 4709-15, 2007.
• Algood, HM, Torres, VJ, Unutmaz, D, Cover, TL Resistance of primary murine CD4+ T cells to Helicobacter pylori vacuolating cytotoxin. Infect Immun, 75(1), 334-41, 2007.
• Ghose, C, Perez-Perez, GI, Torres, VJ, Crosatti, M, Nomura, A, Peek, RM, Cover, TL, Francois, F, Blaser, MJ Serological assays for identification of human gastric colonization by Helicobacter pylori strains expressing VacA m1 or m2. Clin Vaccine Immunol, 14(4), 442-50, 2007.
• Yan, F, Cao, H, Cover, TL, Whitehead, R, Washington, MK, Polk, DB Soluble proteins produced by probiotic bacteria regulate intestinal epithelial cell survival and growth. Gastroenterology, 132(2), 562-75, 2007.
• Oswald-Richter, K, Torres, VJ, Sundrud, MS, VanCompernolle, SE, Cover, TL, Unutmaz, D Helicobacter pylori VacA toxin inhibits human immunodeficiency virus infection of primary human T cells. J Virol, 80(23), 11767-75, 2006.
• Algood, HM, Cover, TL Helicobacter pylori persistence: an overview of interactions between H. pylori and host immune defenses. Clin Microbiol Rev, 19(4), 597-613, 2006.
• Torres, VJ, McClain, MS, Cover, TL Mapping of a domain required for protein-protein interactions and inhibitory activity of a Helicobacter pylori dominant-negative VacA mutant protein. Infect Immun, 74(4), 2093-101, 2006.
• Hennig, EE, Allen, JM, Cover, TL Multiple chromosomal loci for the babA gene in Helicobacter pylori. Infect Immun, 74(5), 3046-51, 2006.
• Busler, VJ, Torres, VJ, McClain, MS, Tirado, O, Friedman, DB, Cover, TL Protein-protein interactions among Helicobacter pylori cag proteins. J Bacteriol, 188(13), 4787-800, 2006.
• Lee, WK, Ogura, K, Loh, JT, Cover, TL, Berg, DE Quantitative effect of luxS gene inactivation on the fitness of Helicobacter pylori. Appl Environ Microbiol, 72(10), 6615-22, 2006.
• McClain, MS, Czajkowsky, DM, Torres, VJ, Szabo, G, Shao, Z, Cover, TL Random mutagenesis of Helicobacter pylori vacA to identify amino acids essential for vacuolating cytotoxic activity. Infect Immun, 74(11), 6188-95, 2006.
• Loh, JT, Cover, TL Requirement of histidine kinases HP0165 and HP1364 for acid resistance in Helicobacter pylori. Infect Immun, 74(5), 3052-9, 2006.
• Cover, TL Role of Helicobacter pylori outer membrane proteins in gastroduodenal disease. J Infect Dis, 194(10), 1343-5, 2006.
• Cao, P, Lee, KJ, Blaser, MJ, Cover, TL Analysis of hopQ alleles in East Asian and Western strains of Helicobacter pylori. FEMS Microbiol Lett, 251(1), 37-43, 2005.
• Torres, VJ, Ivie, SE, McClain, MS, Cover, TL Functional properties of the P33 and P55 domains of the Helicobacter pylori vacuolating cytotoxin. J Biol Chem, 28021107-21114, 2005.
• Terry, CE, McGinnis, LM, Madigan, KC, Cao, P, Cover, TL, Liechti, GW, Peek, RM, Forsyth, MH Genomic Comparison of cag pathogenicity island (PAI)-positive and -negative Helicobacter pylori strains: identification of novel markers for cag PAI-positive strains. Infect Immun, 73(6), 3794-8, 2005.
• Cover, TL, Blanke, SR Helicobacter pylori VacA, a paradigm for toxin multifunctionality. Nat Rev Microbiol, 3(4), 320-32, 2005.
• El-Bez, C, Adrian, M, Dubochet, J, Cover, TL High resolution structural analysis of Helicobacter pylori VacA toxin oligomers by cryo-negative staining electron microscopy. J Struct Biol, 151(3), 215-28, 2005.
• Czajkowsky, DM, Iwamoto, H, Szabo, G, Cover, TL, Shao, Z Mimicry of a host anion channel by a Helicobacter pylori pore-forming toxin. Biophys J, 89(5), 3093-101, 2005.
• Johansson, M, Lehto, M, Tanhuanpää, K, Cover, TL, Olkkonen, VM The Oxysterol-binding Protein Homologue ORP1L Interacts with Rab7 and Alters Functional Properties of Late Endocytic Compartments. Mol Biol Cell, 16(12), 5480-92, 2005.
• Li, Yi, Wandinger-Ness, Angela, Goldenring, James R., Cover, Timothy L. Clustering and redistribution of late endocytic compartments in response to Helicobacter pylori vacuolating toxin. Mol Biol Cell, 15(), 1946-1959, 2004.
• Loh, JT, Forsyth, MH, Cover, TL Growth phase regulation of flaA expression in Helicobacter pylori is luxS dependent. Infect Immun, 72(9), 5506-10, 2004.
• Hennig, EE, Mernaugh, R, Edl, J, Cao, P, Cover, TL Heterogeneity among Helicobacter pylori strains in expression of the outer membrane protein BabA. Infect Immun, 72(6), 3429-35, 2004.
• Sundrud, Mark S., Torres, Victor J., Unutmaz, Derya, Cover, Timothy L. Inhibition of primary human T cell proliferation by Helicobacter pylori vacuolating toxin (VacA) is independent of VacA effects on IL-2 secretion. Proc Natl Acad Sci U S A, 101(20), 7727-7732, 2004.
• Torres, Victor J, McClain, Mark S, Cover, Timothy L Interactions between p-33 and p-55 domains of the Helicobacter pylori vacuolating cytotoxin (VacA). J Biol Chem, 279(3), 2324-31, 2004.
• Geisse, Nicholas, Cover, Timothy, Henderson, Robert, Edwardson, J Targeting of Helicobacter pylori vacuolating toxin to lipid raft membrane domains analysed by atomic force microscopy. Biochem J, 381911-917, 2004.
• Willhite, David C, Cover, Timothy L, Blanke, Steven R Cellular vacuolation and mitochondrial cytochrome c release are independent outcomes of Helicobacter pylori vacuolating cytotoxin activity that are each dependent on membrane channel formation. J Biol Chem, 278(48), 48204-9, 2003.
• Marlink, Katie L, Bacon, Kathy D, Sheppard, Brett C, Ashktorab, Hassan, Smoot, Duane T, Cover, Timothy L, Deveney, Clifford W, Rutten, Michael J Effects of Helicobacter pylori on intracellular Ca2+ signaling in normal human gastric mucous epithelial cells. Am J Physiol Gastrointest Liver Physiol, 285(1), G163-76, 2003.
• McClain, Mark S, Iwamoto, Hideki, Cao, Ping, Vinion-Dubiel, Arlene D, Li, Yi, Szabo, Gabor, Shao, Zhifeng, Cover, Timothy L Essential role of a GXXXG motif for membrane channel formation by Helicobacter pylori vacuolating toxin. J Biol Chem, 278(14), 12101-8, 2003.
• McClain, Mark S, Cover, Timothy L Expression of Helicobacter pylori vacuolating toxin in Escherichia coli. Infect Immun, 71(4), 2266-71, 2003.
• Cover, Timothy L, Krishna, Uma S, Israel, Dawn A, Peek, Richard M Induction of gastric epithelial cell apoptosis by Helicobacter pylori vacuolating cytotoxin. Cancer Res, 63(5), 951-7, 2003.
• McGowan, Catherine C, Necheva, Antoaneta S, Forsyth, Mark H, Cover, Timothy L, Blaser, Martin J Promoter analysis of Helicobacter pylori genes with enhanced expression at low pH. Mol Microbiol, 48(5), 1225-39, 2003.
• Schraw, Wayne, Li, Yi, McClain, Mark S, van der Goot, F Gisou, Cover, Timothy L Association of Helicobacter pylori vacuolating toxin (VacA) with lipid rafts. J Biol Chem, 277(37), 34642-50, 2002.
• Forsyth, Mark H, Cao, Ping, Garcia, Preston P, Hall, Joshua D, Cover, Timothy L Genome-wide transcriptional profiling in a histidine kinase mutant of Helicobacter pylori identifies members of a regulon. J Bacteriol, 184(16), 4630-5, 2002.
• Graham, James E, Peek, Richard M, Krishna, Uma, Cover, Timothy L Global analysis of Helicobacter pylori gene expression in human gastric mucosa. Gastroenterology, 123(5), 1637-48, 2002.
• Drake, Wonder Puryear, Pei, Zhiheng, Pride, David T, Collins, Robert D, Cover, Timothy L, Blaser, Martin J Molecular analysis of sarcoidosis tissues for mycobacterium species DNA. Emerg Infect Dis, 8(11), 1334-41, 2002.
• Adrian, Marc, Cover, Timothy L, Dubochet, Jacques, Heuser, John E Multiple oligomeric states of the Helicobacter pylori vacuolating toxin demonstrated by cryo-electron microscopy. J Mol Biol, 318(1), 121-33, 2002.
• Ikonomov, Ognian C, Sbrissa, Diego, Yoshimori, Tamotsu, Cover, Timothy L, Shisheva, Assia PIKfyve Kinase and SKD1 AAA ATPase define distinct endocytic compartments. Only PIKfyve expression inhibits the cell-vacoulating activity of Helicobacter pylori VacA toxin. J Biol Chem, 277(48), 46785-90, 2002.
• Cao, Ping, Cover, Timothy L Two different families of hopQ alleles in Helicobacter pylori. J Clin Microbiol, 40(12), 4504-11, 2002.
• McClain, M S, Cao, P, Iwamoto, H, Vinion-Dubiel, A D, Szabo, G, Shao, Z, Cover, T L A 12-amino-acid segment, present in type s2 but not type s1 Helicobacter pylori VacA proteins, abolishes cytotoxin activity and alters membrane channel formation. J Bacteriol, 183(22), 6499-508, 2001.
• McClain, M S, Cao, P, Cover, T L Amino-terminal hydrophobic region of Helicobacter pylori vacuolating cytotoxin (VacA) mediates transmembrane protein dimerization. Infect Immun, 69(2), 1181-4, 2001.
• Vinion-Dubiel, A D, McClain, M S, Cao, P, Mernaugh, R L, Cover, T L Antigenic diversity among Helicobacter pylori vacuolating toxins. Infect Immun, 69(7), 4329-36, 2001.
• Nguyen, V Q, Caprioli, R M, Cover, T L Carboxy-terminal proteolytic processing of Helicobacter pylori vacuolating toxin. Infect Immun, 69(1), 543-6, 2001.
• Tham, K T, Peek, R M, Atherton, J C, Cover, T L, Perez-Perez, G I, Shyr, Y, Blaser, M J Helicobacter pylori genotypes, host factors, and gastric mucosal histopathology in peptic ulcer disease. Hum Pathol, 32(3), 264-73, 2001.
• Papini, E, Zoratti, M, Cover, T L In search of the Helicobacter pylori VacA mechanism of action. Toxicon, 39(11), 1757-67, 2001.
• McClain, M S, Schraw, W, Ricci, V, Boquet, P, Cover, T L Acid activation of Helicobacter pylori vacuolating cytotoxin (VacA) results in toxin internalization by eukaryotic cells. Mol Microbiol, 37(2), 433-42, 2000.
• Hotchin, N A, Cover, T L, Akhtar, N Cell vacuolation induced by the VacA cytotoxin of Helicobacter pylori is regulated by the Rac1 GTPase. J Biol Chem, 275(19), 14009-12, 2000.
• Forsyth, M H, Cover, T L Intercellular communication in Helicobacter pylori: luxS is essential for the production of an extracellular signaling molecule. Infect Immun, 68(6), 3193-9, 2000.
• Vinion-Dubiel, A D, McClain, M S, Czajkowsky, D M, Iwamoto, H, Ye, D, Cao, P, Schraw, W, Szabo, G, Blanke, S R, Shao, Z, Cover, T L A dominant negative mutant of Helicobacter pylori vacuolating toxin (VacA) inhibits VacA-induced cell vacuolation. J Biol Chem, 274(53), 37736-42, 1999.
• Perez-Perez, G I, Peek, R M, Atherton, J C, Blaser, M J, Cover, T L Detection of anti-VacA antibody responses in serum and gastric juice samples using type s1/m1 and s2/m2 Helicobacter pylori VacA antigens. Clin Diagn Lab Immunol, 6(4), 489-93, 1999.
• Peek, R M, Blaser, M J, Mays, D J, Forsyth, M H, Cover, T L, Song, S Y, Krishna, U, Pietenpol, J A Helicobacter pylori strain-specific genotypes and modulation of the gastric epithelial cell cycle. Cancer Res, 59(24), 6124-31, 1999.
• Pai, R, Cover, T L, Tarnawski, A S Helicobacter pylori vacuolating cytotoxin (VacA) disorganizes the cytoskeletal architecture of gastric epithelial cells. Biochem Biophys Res Commun, 262(1), 245-50, 1999.
• Schraw, W, McClain, M S, Cover, T L Kinetics and mechanisms of extracellular protein release by Helicobacter pylori. Infect Immun, 67(10), 5247-52, 1999.
• Forsyth, M H, Cover, T L Mutational analysis of the vacA promoter provides insight into gene transcription in Helicobacter pylori. J Bacteriol, 181(7), 2261-6, 1999.
• Fiocca, R, Necchi, V, Sommi, P, Ricci, V, Telford, J, Cover, T L, Solcia, E Release of Helicobacter pylori vacuolating cytotoxin by both a specific secretion pathway and budding of outer membrane vesicles. Uptake of released toxin and vesicles by gastric epithelium. J Pathol, 188(2), 220-6, 1999.
• Atherton, J C, Cover, T L, Twells, R J, Morales, M R, Hawkey, C J, Blaser, M J Simple and accurate PCR-based system for typing vacuolating cytotoxin alleles of Helicobacter pylori. J Clin Microbiol, 37(9), 2979-82, 1999.
• Czajkowsky, D M, Iwamoto, H, Cover, T L, Shao, Z The vacuolating toxin from Helicobacter pylori forms hexameric pores in lipid bilayers at low pH. Proc Natl Acad Sci U S A, 96(5), 2001-6, 1999.
• Iwamoto, H, Czajkowsky, D M, Cover, T L, Szabo, G, Shao, Z VacA from Helicobacter pylori: a hexameric chloride channel. FEBS Lett, 450(1-2), 101-4, 1999.
• Atherton, J C, Sharp, P M, Cover, T L, Gonzalez-Valencia, G, Peek, R M, Thompson, S A, Hawkey, C J, Blaser, M J Vacuolating cytotoxin (vacA) alleles of Helicobacter pylori comprise two geographically widespread types, m1 and m2, and have evolved through limited recombination. Curr Microbiol, 39(4), 211-8, 1999.
• McGowan, C C, Necheva, A, Thompson, S A, Cover, T L, Blaser, M J Acid-induced expression of an LPS-associated gene in Helicobacter pylori. Mol Microbiol, 30(1), 19-31, 1998.
• Cao, P, McClain, M S, Forsyth, M H, Cover, T L Extracellular release of antigenic proteins by Helicobacter pylori. Infect Immun, 66(6), 2984-6, 1998.
• Pai, R, Wyle, F A, Cover, T L, Itani, R M, Domek, M J, Tarnawski, A S Helicobacter pylori culture supernatant interferes with epidermal growth factor-activated signal transduction in human gastric KATO III cells. Am J Pathol, 152(6), 1617-24, 1998.
• Romano, M, Ricci, V, Di Popolo, A, Sommi, P, Del Vecchio Blanco, C, Bruni, C B, Ventura, U, Cover, T L, Blaser, M J, Coffey, R J, Zarrilli, R Helicobacter pylori upregulates expression of epidermal growth factor-related peptides, but inhibits their proliferative effect in MKN 28 gastric mucosal cells. J Clin Invest, 101(8), 1604-13, 1998.
• Forsyth, M H, Atherton, J C, Blaser, M J, Cover, T L Heterogeneity in levels of vacuolating cytotoxin gene (vacA) transcription among Helicobacter pylori strains. Infect Immun, 66(7), 3088-94, 1998.
• Pagliaccia, C, de Bernard, M, Lupetti, P, Ji, X, Burroni, D, Cover, T L, Papini, E, Rappuoli, R, Telford, J L, Reyrat, J M The m2 form of the Helicobacter pylori cytotoxin has cell type-specific vacuolating activity. Proc Natl Acad Sci U S A, 95(17), 10212-7, 1998.
• Cover, T L, Hanson, P I, Heuser, J E Acid-induced dissociation of VacA, the Helicobacter pylori vacuolating cytotoxin, reveals its pattern of assembly. J Cell Biol, 138(4), 759-69, 1997.
• McGowan, C C, Cover, T L, Blaser, M J Analysis of F1F0-ATPase from Helicobacter pylori. Infect Immun, 65(7), 2640-7, 1997.
• Atherton, J C, Peek, R M, Tham, K T, Cover, T L, Blaser, M J Clinical and pathological importance of heterogeneity in vacA, the vacuolating cytotoxin gene of Helicobacter pylori. Gastroenterology, 112(1), 92-9, 1997.
• Cover, T L Genetic diversity in Helicobacter pylori. Helicobacter, 2(2), 108-9, 1997.
• Cao, P, Cover, T L High-level genetic diversity in the vapD chromosomal region of Helicobacter pylori. J Bacteriol, 179(9), 2852-6, 1997.
• Eaton, K A, Cover, T L, Tummuru, M K, Blaser, M J, Krakowka, S Role of vacuolating cytotoxin in gastritis due to Helicobacter pylori in gnotobiotic piglets. Infect Immun, 65(8), 3462-4, 1997.
• Garner, J A, Cover, T L Binding and internalization of the Helicobacter pylori vacuolating cytotoxin by epithelial cells. Infect Immun, 64(10), 4197-203, 1996.
• Atherton, J C, Tham, K T, Peek, R M, Cover, T L, Blaser, M J Density of Helicobacter pylori infection in vivo as assessed by quantitative culture and histology. J Infect Dis, 174(3), 552-6, 1996.
• Ricci, V, Ciacci, C, Zarrilli, R, Sommi, P, Tummuru, M K, Del Vecchio Blanco, C, Bruni, C B, Cover, T L, Blaser, M J, Romano, M Effect of Helicobacter pylori on gastric epithelial cell migration and proliferation in vitro: role of VacA and CagA. Infect Immun, 64(7), 2829-33, 1996.
• Smoot, D T, Resau, J H, Earlington, M H, Simpson, M, Cover, T L Effects of Helicobacter pylori vacuolating cytotoxin on primary cultures of human gastric epithelial cells. Gut, 39(96), 795-9, 1996.
• McGowan, C C, Cover, T L, Blaser, M J Helicobacter pylori and gastric acid: biological and therapeutic implications. Gastroenterology, 110(3), 926-38, 1996.
• Harris, P R, Cover, T L, Crowe, D R, Orenstein, J M, Graham, M F, Blaser, M J, Smith, P D Helicobacter pylori cytotoxin induces vacuolation of primary human mucosal epithelial cells. Infect Immun, 64(11), 4867-71, 1996.
• Cover, T L, Blaser, M J Helicobacter pylori infection, a paradigm for chronic mucosal inflammation: pathogenesis and implications for eradication and prevention. Adv Intern Med, 4185-117, 1996.
• Cover, T L The vacuolating cytotoxin of Helicobacter pylori. Mol Microbiol, 20(2), 241-6, 1996.
• Garner, J A, Cover, T L Analysis of genetic diversity in cytotoxin-producing and non-cytotoxin-producing Helicobacter pylori strains. J Infect Dis, 172(1), 290-3, 1995.
• Peek, R M, Miller, G G, Tham, K T, Pérez-Pérez, G I, Cover, T L, Atherton, J C, Dunn, G D, Blaser, M J Detection of Helicobacter pylori gene expression in human gastric mucosa. J Clin Microbiol, 33(1), 28-32, 1995.
• Blaser, M J, Perez-Perez, G I, Kleanthous, H, Cover, T L, Peek, R M, Chyou, P H, Stemmermann, G N, Nomura, A Infection with Helicobacter pylori strains possessing cagA is associated with an increased risk of developing adenocarcinoma of the stomach. Cancer Res, 55(10), 2111-5, 1995.
• Atherton, J C, Cao, P, Peek, R M, Tummuru, M K, Blaser, M J, Cover, T L Mosaicism in vacuolating cytotoxin alleles of Helicobacter pylori. Association of specific vacA types with cytotoxin production and peptic ulceration. J Biol Chem, 270(30), 17771-7, 1995.
• Ghiara, P, Marchetti, M, Blaser, M J, Tummuru, M K, Cover, T L, Segal, E D, Tompkins, L S, Rappuoli, R Role of the Helicobacter pylori virulence factors vacuolating cytotoxin, CagA, and urease in a mouse model of disease. Infect Immun, 63(10), 4154-60, 1995.
• Cover, T L, Glupczynski, Y, Lage, A P, Burette, A, Tummuru, M K, Perez-Perez, G I, Blaser, M J Serologic detection of infection with cagA+ Helicobacter pylori strains. J Clin Microbiol, 33(6), 1496-500, 1995.
• Pérez-Pérez, G I, Brown, W R, Cover, T L, Dunn, B E, Cao, P, Blaser, M J Correlation between serological and mucosal inflammatory responses to Helicobacter pylori. Clin Diagn Lab Immunol, 1(3), 325-9, 1994.
• Cover, T L, Tummuru, M K, Cao, P, Thompson, S A, Blaser, M J Divergence of genetic sequences for the vacuolating cytotoxin among Helicobacter pylori strains. J Biol Chem, 269(14), 10566-73, 1994.
• Tummuru, M K, Cover, T L, Blaser, M J Mutation of the cytotoxin-associated cagA gene does not affect the vacuolating cytotoxin activity of Helicobacter pylori. Infect Immun, 62(6), 2609-13, 1994.
• McGowan, C C, Cover, T L, Blaser, M J The proton pump inhibitor omeprazole inhibits acid survival of Helicobacter pylori by a urease-independent mechanism. Gastroenterology, 107(3), 738-43, 1994.
• McGowan, C C, Cover, T L, Blaser, M J The proton pump inhibitor omeprazole inhibits acid survival of Helicobacter pylori by a urease-independent mechanism. Gastroenterology, 107(5), 1573-8, 1994.
• Tummuru, M K, Cover, T L, Blaser, M J Cloning and expression of a high-molecular-mass major antigen of Helicobacter pylori: evidence of linkage to cytotoxin production. Infect Immun, 61(5), 1799-809, 1993.
• Cover, T L, Cao, P, Lind, C D, Tham, K T, Blaser, M J Correlation between vacuolating cytotoxin production by Helicobacter pylori isolates in vitro and in vivo. Infect Immun, 61(12), 5008-12, 1993.
• Cover, T L, Reddy, L Y, Blaser, M J Effects of ATPase inhibitors on the response of HeLa cells to Helicobacter pylori vacuolating toxin. Infect Immun, 61(4), 1427-31, 1993.
• Blaser, M J, Kobayashi, K, Cover, T L, Cao, P, Feurer, I D, Pérez-Pérez, G I Helicobacter pylori infection in Japanese patients with adenocarcinoma of the stomach. Int J Cancer, 55(5), 799-802, 1993.
• Cover, T L, Blaser, M J Purification and characterization of the vacuolating toxin from Helicobacter pylori. J Biol Chem, 267(15), 10570-5, 1992.
• Cover, T L, Cao, P, Murthy, U K, Sipple, M S, Blaser, M J Serum neutralizing antibody response to the vacuolating cytotoxin of Helicobacter pylori. J Clin Invest, 90(3), 913-8, 1992.