John T. Loh, Ph.D.

Research Associate Professor
Faculty Appointments
Research Associate Professor of Medicine
Ph.D., Biochemistry, Michigan State University, East Lansing, MichiganB.Sc., Biochemistry, Michigan State University, East Lansing, Michigan
Office Address
F-525 ACRE Bldg.
Nashville, TN 37212-2582
Research Description
The bacterial pathogen Helicobacter pylori colonizes the human gastric mucosa and has been implicated as an essential factor leading to gastritis, duodenal ulcers and gastric adenocarcinoma. I am investigating pathways that regulate gene expression in this organism. Specifically, my work has focused on understanding how H. pylori controls expression of its genes in response to the small molecule autoinducer AI-2 produced by the bacteria. When autoinducers such as AI-2 reach a threshold concentration, they interact with bacterial regulatory components, resulting in population dependent changes in gene expression. We have used microarrays to identify putative genes that are regulated by AI-2. From this pool, we have utilized gene reporter systems to validate the microarray results. We hope that by using this two-step method of identification and validation, we will be able to identify components that are necessary for establishment and maintenance of H. pylori. Other areas of interest include investigation of two-component signal transduction systems that regulate H. pylori gene expression, and analysis of factors produced by host cells that alter bacterial gene expression.

Research Keywords
Helicobacter pylori gene regulation
Shaffer CL, Good JA, Kumar S, Krishnan KS, Gaddy JA, Loh JT, Chappell J, Almqvist F, Cover TL, Hadjifrangiskou M. Peptidomimetic Small Molecules Disrupt Type IV Secretion System Activity in Diverse Bacterial Pathogens. MBio. 2016 Apr 4/26/2016; 7(2): e00221-16. PMID: 27118587, PMCID: PMC4850256, PII: mBio.00221-16, DOI: 10.1128/mBio.00221-16, ISSN: 2150-7511.

Loh JT, Gaddy JA, Algood HM, Gaudieri S, Mallal S, Cover TL. Helicobacter pylori adaptation in vivo in response to a high-salt diet. Infect. Immun [print-electronic]. 2015 Dec; 83(12): 4871-83. PMID: 26438795, PMCID: PMC4645402, PII: IAI.00918-15, DOI: 10.1128/IAI.00918-15, ISSN: 1098-5522.

Voss BJ, Loh JT, Hill S, Rose KL, McDonald WH, Cover TL. Alteration of the Helicobacter pylori membrane proteome in response to changes in environmental salt concentration. Proteomics Clin Appl [print-electronic]. 2015 Dec; 9(11-12): 1021-34. PMID: 26109032, PMCID: PMC4690801, DOI: 10.1002/prca.201400176, ISSN: 1862-8354.

Gaddy JA, Radin JN, Loh JT, Piazuelo MB, Kehl-Fie TE, Delgado AG, Ilca FT, Peek RM, Cover TL, Chazin WJ, Skaar EP, Scott Algood HM. The host protein calprotectin modulates the Helicobacter pylori cag type IV secretion system via zinc sequestration. PLoS Pathog. 2014 Oct; 10(10): e1004450. PMID: 25330071, PMCID: PMC4199781, PII: PPATHOGENS-D-14-01130, DOI: 10.1371/journal.ppat.1004450, ISSN: 1553-7374.

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 [print-electronic]. 2013 Jun; 81(6): 2258-67. PMID: 23569116, PMCID: PMC3676043, PII: IAI.01271-12, DOI: 10.1128/IAI.01271-12, ISSN: 1098-5522.

Radin JN, Gaddy JA, González-Rivera C, Loh JT, Algood HM, Cover TL. Flagellar localization of a Helicobacter pylori autotransporter protein. MBio. 2013 Apr 4/9/2013; 4(2): e00613-12. PMID: 23572556, PMCID: PMC3622936, PII: mBio.00613-12, DOI: 10.1128/mBio.00613-12, ISSN: 2150-7511.

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 [print-electronic]. 2012 Sep; 80(9): 3094-106. PMID: 22710874, PMCID: PMC3418733, PII: IAI.00232-12, DOI: 10.1128/IAI.00232-12, ISSN: 1098-5522.

Sicinschi LA, Correa P, Bravo LE, Peek RM, Wilson KT, Loh JT, Yepez MC, Gold BD, Thompson DT, Cover TL, Schneider BG. Non-invasive genotyping of Helicobacter pylori cagA, vacA, and hopQ from asymptomatic children. Helicobacter. 2012 Apr; 17(2): 96-106. PMID: 22404439, PMCID: PMC3305281, DOI: 10.1111/j.1523-5378.2011.00919.x, ISSN: 1523-5378.

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 [print-electronic]. 2011 Oct; 20(10): 2237-49. PMID: 21859954, PMCID: PMC3189306, PII: 1055-9965.EPI-11-0548, DOI: 10.1158/1055-9965.EPI-11-0548, ISSN: 1538-7755.

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 [print-electronic]. 2011 Sep; 7(9): e1002237. PMID: 21909278, PMCID: PMC3164655, PII: PPATHOGENS-D-11-00533, DOI: 10.1371/journal.ppat.1002237, ISSN: 1553-7374.

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 [print-electronic]. 2010 Apr; 192(8): 2034-43. PMID: 20154125, PMCID: PMC2849440, PII: JB.01703-08, DOI: 10.1128/JB.01703-08, ISSN: 1098-5530.

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. 2008 Dec; 289(1): 53-8. PMID: 19065710, PMCID: PMC2651568, ISSN: 0378-1097.

Loh JT, Torres VJ, Cover TL. Regulation of Helicobacter pylori cagA expression in response to salt. Cancer Res. 2007 May 5/15/2007; 67(10): 4709-15. PMID: 17510398, PII: 67/10/4709, DOI: 10.1158/0008-5472.CAN-06-4746, ISSN: 0008-5472.

Loh JT, Cover TL. Requirement of histidine kinases HP0165 and HP1364 for acid resistance in Helicobacter pylori. Infect. Immun. 2006 May; 74(5): 3052-9. PMID: 16622250, PMCID: PMC1459715, PII: 74/5/3052, DOI: 10.1128/IAI.74.5.3052-3059.2006, ISSN: 0019-9567.

Loh JT, Forsyth MH, Cover TL. Growth phase regulation of flaA expression in Helicobacter pylori is luxS dependent. Infect. Immun. 2004 Sep; 72(9): 5506-10. PMID: 15322055, PMCID: PMC517482, PII: 72/9/5506, DOI: 10.1128/IAI.72.9.5506-5510.2004, ISSN: 0019-9567.

Loh J, Stacey G. Nodulation gene regulation in Bradyrhizobium japonicum: a unique integration of global regulatory circuits. Appl. Environ. Microbiol. 2003 Jan; 69(1): 10-7. PMID: 12513971, PMCID: PMC152446, ISSN: 0099-2240.

Loh J, Carlson RW, York WS, Stacey G. Bradyoxetin, a unique chemical signal involved in symbiotic gene regulation. Proc. Natl. Acad. Sci. U.S.A [print-electronic]. 2002 Oct 10/29/2002; 99(22): 14446-51. PMID: 12393811, PMCID: PMC137903, PII: 222336799, DOI: 10.1073/pnas.222336799, ISSN: 0027-8424.

Loh J, Pierson EA, Pierson LS, Stacey G, Chatterjee A. Quorum sensing in plant-associated bacteria. Curr. Opin. Plant Biol. 2002 Aug; 5(4): 285-90. PMID: 12179960, ISSN: 1369-5266.

Loh J, Lohar DP, Andersen B, Stacey G. A two-component regulator mediates population-density-dependent expression of the Bradyrhizobium japonicum nodulation genes. J. Bacteriol. 2002 Mar; 184(6): 1759-66. PMID: 11872728, PMCID: PMC134882, ISSN: 0021-9193.

Loh JT, Yuen-Tsai JP, Stacey MG, Lohar D, Welborn A, Stacey G. Population density-dependent regulation of the Bradyrhizobium japonicum nodulation genes. Mol. Microbiol. 2001 Oct; 42(1): 37-46. PMID: 11679065, PII: 2625, ISSN: 0950-382X.

Loh JT, Stacey G. Feedback regulation of the Bradyrhizobium japonicum nodulation genes. Mol. Microbiol. 2001 Sep; 41(6): 1357-64. PMID: 11580840, PII: 2603, ISSN: 0950-382X.

Tomkins JP, Wood TC, Stacey MG, Loh JT, Judd A, Goicoechea JL, Stacey G, Sadowsky MJ, Wing RA. A marker-dense physical map of the Bradyrhizobium japonicum genome. Genome Res. 2001 Aug; 11(8): 1434-40. PMID: 11483585, PMCID: PMC311109, DOI: 10.1101/gr.185001, ISSN: 1088-9051.

Day RB, McAlvin CB, Loh JT, Denny RL, Wood TC, Young ND, Stacey G. Differential expression of two soybean apyrases, one of which is an early nodulin. Mol. Plant Microbe Interact. 2000 Oct; 13(10): 1053-70. PMID: 11043467, DOI: 10.1094/MPMI.2000.13.10.1053, ISSN: 0894-0282.

Loh J, Stacey MG, Sadowsky MJ, Stacey G. The Bradyrhizobium japonicum nolA gene encodes three functionally distinct proteins. J. Bacteriol. 1999 Mar; 181(5): 1544-54. PMID: 10049387, PMCID: PMC93545, ISSN: 0021-9193.

Loh J, Garcia M, Stacey G. NodV and NodW, a second flavonoid recognition system regulating nod gene expression in Bradyrhizobium japonicum. J. Bacteriol. 1997 May; 179(9): 3013-20. PMID: 9139921, PMCID: PMC179067, ISSN: 0021-9193.

Garcia M, Dunlap J, Loh J, Stacey G. Phenotypic characterization and regulation of the nolA gene of Bradyrhizobium japonicum. Mol. Plant Microbe Interact. 1996 Sep; 9(7): 625-36. PMID: 8810078, ISSN: 0894-0282.

Loh JT, Ho SC, Wang JL, Schindler M. Carbohydrate binding activities of Bradyrhizobium japonicum: IV. Effect of lactose and flavones on the expression of the lectin, BJ38. Glycoconj. J. 1994 Aug; 11(4): 363-70. PMID: 7873932, ISSN: 0282-0080.

Ho SC, Wang JL, Schindler M, Loh JT. Carbohydrate binding activities of Bradyrhizobium japonicum. III. Lectin expression, bacterial binding, and nodulation efficiency. Plant J. 1994 Jun; 5(6): 873-84. PMID: 8054992, ISSN: 0960-7412.

Loh JT, Ho SC, de Feijter AW, Wang JL, Schindler M. Carbohydrate binding activities of Bradyrhizobium japonicum: unipolar localization of the lectin BJ38 on the bacterial cell surface. Proc. Natl. Acad. Sci. U.S.A. 1993 Apr 4/1/1993; 90(7): 3033-7. PMID: 8464919, PMCID: PMC46231, ISSN: 0027-8424.