Department of Pathology, Microbiology, and Immunology



Timothy L. Cover, M.D.c




Dept. of Medicine


Dept. of Pathology, Microbiology and Immunology



Contact Information



Office Location:
MCN A-2320

Phone: 615-343-8753

E-mail:  timothy.L.cover@vanderbilt.edu


Campus Mail address:

Dept. of Medicine

Division of Infectious Diseases

MCN A-2200 (2582)


US Mailing address:
Vanderbilt University School of Medicine

Department of Medicine
Division of Infectious Diseases

MCN A-2200
Nashville, TN 37232-2582







M.D., Duke University, Durham, NC
B.S., Muhlenberg College, Allentown, PA



Research Keywords



Pathogenesis of bacterial infections, Bacteria-host interactions, Bacterial protein toxins, Helicobacter pylori, Gastric cancer, Bacterial virulence determinants, Bacteria, Cancer, Genomics, Infectious disease, Microbiology, Immunology, Protein structure, Evasion of host defenses



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.



Clinical Research Description








Radin, JN, Gonz??lez-Rivera, C, Frick-Cheng, AE, Sheng, J, Gaddy, JA, Rubin, DH, Algood, HM, McClain, MS, Cover, TL. Role of Connexin 43 in Helicobacter pylori VacA-Induced Cell Death. Infect Immun, 82(1), 423-32, 2014

Johnson, EM, Gaddy, JA, Voss, BJ, Hennig, EE, Cover, TL. Genes Required for Assembly of Pili Associated with the Helicobacter pylori cag Type IV Secretion System. Infect Immun, 82(8), 3457-70, 2014

Engler, DB, Reuter, S, van Wijck, Y, Urban, S, Kyburz, A, Maxeiner, J, Martin, H, Yogev, N, Waisman, A, Gerhard, M, Cover, TL, Taube, C, M??ller, A. Effective treatment of allergic airway inflammation with Helicobacter pylori immunomodulators requires BATF3-dependent dendritic cells and IL-10. Proc Natl Acad Sci U S A, 2014

Voss, BJ, Gaddy, JA, McDonald, WH, Cover, TL. Analysis of Surface-Exposed Outer Membrane Proteins in Helicobacter pylori. J Bacteriol, 196(13), 2455-71, 2014

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, 111(4), 1455-60, 2014

Parekh, VV, Wu, L, Boyd, KL, Williams, JA, Gaddy, JA, Olivares-Villag??mez, D, Cover, TL, Zong, WX, Zhang, J, Van Kaer, L. Impaired autophagy, defective T cell homeostasis, and a wasting syndrome in mice with a T cell-specific deletion of Vps34. J Immunol, 190(10), 5086-101, 2013

McClain, MS, Duncan, SS, Gaddy, JA, Cover, TL. Control of gene expression in Helicobacter pylori using the Tet repressor. J Microbiol Methods, 95(3), 336-341, 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, 81(6), 2258-67, 2013

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

Duncan, SS, Bertoli, MT, Kersulyte, D, Valk, PL, Tamma, S, Segal, I, McClain, MS, Cover, TL, Berg, DE. Genome Sequences of Three hpAfrica2 Strains of Helicobacter pylori. Genome Announc, 1(5), 2013

Cover, TL, Peek, RM. Diet, microbial virulence and Helicobacter pylori-induced gastric cancer. Gut Microbes, 4(6), 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

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

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), e00613-12, 2013

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, 2, 70, 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

Johnson, EM, Gaddy, JA, Cover, TL. Alterations in Helicobacter pylori Triggered by Contact with Gastric Epithelial Cells. Front Cell Infect Microbiol, 2, 17, 2012

Cover, TL. Perspectives on methodology for in vitro culture of Helicobacter pylori. Methods Mol Biol, 921, 11-5, 2012

Gonz?!lez-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

Cover, TL. Role of Helicobacter pylori CagL in modulating gastrin expression. Gut, 61(7), 965-6, 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

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

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, Gonz?!lez-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

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. I?-Catenin and p120 mediate PPARI'-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, 10, 60, 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, 10, 210, 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

Gonz?!lez-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

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

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

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, Blaser, MJ. Helicobacter pylori in health and disease. Gastroenterology, 136(6), 1863-73, 2009

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

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

Cover, TL. Beta2 integrin mediates entry of a bacterial toxin into T lymphocytes. Cell Host Microbe, 3(1), 5-6, 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

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

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

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

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, 51, 577-586, 2007

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

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

McClain, MS, Cover, TL. Functional analysis of neutralizing antibodies against Clostridium perfringens epsilon-toxin. Infect Immun, 75(4), 1785-93, 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

Loh, JT, Torres, VJ, Cover, TL. Regulation of Helicobacter pylori cagA expression in response to salt. Cancer Res, 67(10), 4709-15, 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

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

Cover, TL. Role of Helicobacter pylori outer membrane proteins in gastroduodenal disease. J Infect Dis, 194(10), 1343-5, 2006

Hennig, EE, Allen, JM, Cover, TL. Multiple chromosomal loci for the babA gene in Helicobacter pylori. Infect Immun, 74(5), 3046-51, 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

Loh, JT, Cover, TL. Requirement of histidine kinases HP0165 and HP1364 for acid resistance in Helicobacter pylori. Infect Immun, 74(5), 3052-9, 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

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

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

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

Johansson, M, Lehto, M, Tanhuanp????, 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

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, 280, 21107-21114, 2005

Cover, TL, Blanke, SR. Helicobacter pylori VacA, a paradigm for toxin multifunctionality. Nat Rev Microbiol, 3(4), 320-32, 2005

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

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

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

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

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

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, 381, 911-917, 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

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

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

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

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

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

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

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

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

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

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

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

Cao, Ping, Cover, Timothy L. Two different families of hopQ alleles in Helicobacter pylori. J Clin Microbiol, 40(12), 4504-11, 2002

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

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

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

Papini, E, Zoratti, M, Cover, T L. In search of the Helicobacter pylori VacA mechanism of action. Toxicon, 39(11), 1757-67, 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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

McGowan, C C, Cover, T L, Blaser, M J. Analysis of F1F0-ATPase from Helicobacter pylori. Infect Immun, 65(7), 2640-7, 1997

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

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

Cover, T L. The vacuolating cytotoxin of Helicobacter pylori. Mol Microbiol, 20(2), 241-6, 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

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

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, 41, 85-117, 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

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

Peek, R M, Miller, G G, Tham, K T, P??rez-P??rez, 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

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

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

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. Mutation of the cytotoxin-associated cagA gene does not affect the vacuolating cytotoxin activity of Helicobacter pylori. Infect Immun, 62(6), 2609-13, 1994

P??rez-P??rez, 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

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

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

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

Blaser, M J, Kobayashi, K, Cover, T L, Cao, P, Feurer, I D, P??rez-P??rez, G I. Helicobacter pylori infection in Japanese patients with adenocarcinoma of the stomach. Int J Cancer, 55(5), 799-802, 1993

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, 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

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

Cover, T L, Blaser, M J. Purification and characterization of the vacuolating toxin from Helicobacter pylori. J Biol Chem, 267(15), 10570-5, 1992