Vanderbilt University School of Medicine

Cover, Timothy L. , M.D.
Professor of Medicine
Professor of Pathology, Microbiology and Immunology

Lab Url: N/A

Phone Number: 615-322-2035


Cover, Timothy's picture

Office Address   Mailing Address

A2320 MCN

Division of Infectious Diseases A2200 Medical Center North 37232

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 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.

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.

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.

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.

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.

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.

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.

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.

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

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.

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.

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.

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.

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.

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.

Cover, TL. Role of Helicobacter pylori CagL in modulating gastrin expression. Gut, 61(7), 965-6, 2012.

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

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.

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

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. PMCID:3164655

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. PMCID:3164655

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. PMCID:3104743

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. PMCID:3164655

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. PMCID:3104743

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. PMCID:3133872

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. PMCID:2981223

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. PMCID:2910095

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. PMCID:2836311

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. PMCID:2836311

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. PMCID:2923134

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. PMCID:2834183

Cover, TL, Blaser, MJ. Helicobacter pylori in health and disease. Gastroenterology, 136(6), 1863-73, 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. PMCID:2649097

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. PMCID:2627912

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.

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. PMCID:2553690

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. PMCID:2446698

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. PMCID:2651568

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. PMCID:2546541

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. PMCID:1828377

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. PMCID:1951193

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. PMCID:2042200

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. PMCID:1865612

Loh, JT, Torres, VJ, Cover, TL. Regulation of Helicobacter pylori cagA expression in response to salt. Cancer Res, 67(10), 4709-15, 2007.

McClain, MS, Cover, TL. Functional analysis of neutralizing antibodies against Clostridium perfringens epsilon-toxin. Infect Immun, 75(4), 1785-93, 2007. PMCID:1865726

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.

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.

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.

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. PMCID:1592695

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. PMCID:1482994

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. PMCID:1459736

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. PMCID:1610275

Loh, JT, Cover, TL. Requirement of histidine kinases HP0165 and HP1364 for acid resistance in Helicobacter pylori. Infect Immun, 74(5), 3052-9, 2006. PMCID:1459715

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. PMCID:1695532

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. PMCID:1642621

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. PMCID:1418911

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.

Cover, TL, Blanke, SR. Helicobacter pylori VacA, a paradigm for toxin multifunctionality. Nat Rev Microbiol, 3(4), 320-32, 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. PMCID:1366806

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.

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. PMCID:1289395

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. PMCID:1111835

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.

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. PMCID:1133903

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. PMCID:415674

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. PMCID:379289

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. PMCID:517482

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. PMCID:419674

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.

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.

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, Cover, Timothy L. Expression of Helicobacter pylori vacuolating toxin in Escherichia coli. Infect Immun, 71(4), 2266-71, 2003. PMCID:152094

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.

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.

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.

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.

Cao, Ping, Cover, Timothy L. Two different families of hopQ alleles in Helicobacter pylori. J Clin Microbiol, 40(12), 4504-11, 2002. PMCID:154617

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. PMCID:2738555

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. PMCID:135264

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. PMCID:1361305

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.

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.

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. PMCID:98002

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. PMCID:95478

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. PMCID:97915

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

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. PMCID:98503

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. PMCID:97560

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.

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.

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. PMCID:85427

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.

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. PMCID:26726

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.

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. PMCID:93642

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.

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.

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.

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. PMCID:95713

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. PMCID:96877

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.

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. PMCID:108299

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. PMCID:108317

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. PMCID:21487

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. PMCID:1858446

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. PMCID:508741

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.

Cao, P, Cover, T L. High-level genetic diversity in the vapD chromosomal region of Helicobacter pylori. J Bacteriol, 179(9), 2852-6, 1997. PMCID:179045

Cover, T L. Genetic diversity in Helicobacter pylori. Helicobacter, 2(2), 108-9, 1997.

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. PMCID:2138037

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. PMCID:175490

McGowan, C C, Cover, T L, Blaser, M J. Analysis of F1F0-ATPase from Helicobacter pylori. Infect Immun, 65(7), 2640-7, 1997. PMCID:175373

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

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. PMCID:174356

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. PMCID:174461

McGowan, C C, Cover, T L, Blaser, M J. Helicobacter pylori and gastric acid: biological and therapeutic implications. Gastroenterology, 110(3), 926-38, 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. PMCID:174149

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. PMCID:1383449

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.

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.

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. PMCID:228203

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.

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. PMCID:173584

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. PMCID:227873

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.

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.

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. PMCID:368256

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. PMCID:186552

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.

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. PMCID:281276

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. PMCID:281381

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. PMCID:280768

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. PMCID:329946

Postdoctoral Position Available

Postdoctoral Position Details
Postdoctoral position available to study the molecular pathogenesis of Helicobacter pylori infection and mechanisms by which H. pylori infection leads to gastric cancer. Areas of interest in the laboratory include a broad range of topics, including investigation of two H. pylori toxins (VacA and CagA), investigation of a type IV secretion system encoded by the H. pylori cag pathogenicity island, regulation of H. pylori gene expression, and comparative genome sequence analysis of H. pylori strains isolated from patients with different disease states. Please send CV to Dr. Timothy L. Cover, Division of Infectious Diseases, A2200 Medical Center North, Vanderbilt University School of Medicine, Nashville, TN 37232. Email:

Updated Date