Research Focus

James G. Fox has had a long standing research interest in infectious diseases of the gastrointestinal tract and their oncogenic potential. The ferret has been developed in his laboratory as an experimental model because this species has many similarities in anatomy and physiology to those observed in the human. For example, the Fox lab has used the ferret on NIH supported grants as (1) a model of carotenoid metabolism (2) to study enteric campylobacteriosis and (3) investigations regarding proliferative bowel disease caused by a novel Desulfovibrio sp. Also the pathogenic bacterium, Helicobacter mustelae in the ferret gastric mucosa has been extensively characterized. This bacterium causes inflammatory lesions, including ulcers and multifocal atrophic gastritis, a premalignant lesion as well as being directly linked to gastric adenocarcinoma and MALT lymphoma. This finding is of considerable interest in connection with studies of Helicobacter pylori gastric infection in humans and its relationship to gastritis, ulcers, and most recently gastric adenocarcinoma and MALT lymphoma. A mouse model of Helicobacter-induced gastritis developed in our laboratory is also being used to study pathogenesis, therapeutic modalities and immunization strategies. His laboratory also isolated, characterized, and named H. hepaticus, which is responsible for a new murine disease, "H. hepaticus induced hepatitis." In A/JCr mice and B6C3F1 (the mouse hybrid used in NTP carcinogenesis bioassays), the organism induces hepatic adenomas and heptocellular carcinomas. Ongoing studies are designed to determine in vivo molecular events operable in the tumorigenic process.

Selected Publications

Saunders KE, Shen Z, Dewhirst FE, Paster BJ, Dangler CA, Fox JG. Novel intestinal Helicobacter species isolated from cotton-top tamarins (Saguinus oedipus) with chronic colitis. J Clin Microbiol 37:146-151, 1999.

Lichtenberger LM, Dial EJ, Ottlecz A, Romero JJ, Lechago J, Fox JG. Attenuation of hydrophobic phospholipid barrier is an early event in Helicobacter felis-induced gastritis in mice. Dig Dis Sci 44: 108-115, 1999.

Jackson L, Trudel LJ, Fox JG, Lipman NS. Monoclonal antibody production in murine ascites I: Clinical and pathological features. Lab Anim Sci 49: 70-80, 1999.

Jackson L, Trudel LJ, Fox JG, Lipman NS. Monoclonal antibody production in murine ascites II: Production characteristics. Lab Anim Sci 49:81-86, 1999.

Fox JG, Gorelick PL, Kullberg M, Ge Z, Dewhirst FE, Ward JM. A novel urease negative Helicobacter species associated with colitis and typhlitis in IL-10 deficient mice. Infection and Immunity 67:1757-1762, 1999.

Koh TJ, Dockray GJ, Varro A, Cahill RJ, Dangler CA, Fox JG, Wang TC. Overexpression of glycine-extended gastrin in transgenic mice results in increased colonic proliferation. J Clin Invest 103: 1119-1126, 1999.

Ihrig M, Schrenzel M, Fox JG. Differential susceptibility to hepatic inflammation and proliferation in AXB recombinant inbred mice chronically infected with Helicobacter hepaticus. Am J Pathol 155: 571-582, 1999.
Jacoby RO, Fox JG. Federal support for training in laboratory animal medicine should be reinstated (editorial). Lab Anim Sci 49: 348, 1999.

Shomer NH, Astrofsky KM, Dangler CA, Fox JG. Biomethod for obtaining gastric juice and serum from the unanesthetized guinea pig (Cavia porcellus). Contemporary Topics in LAS 38: 32-35, 1999

Dewhirst FE, Chien CC, Paster BJ, Ericson RL, Orcutt R, Schauer DB, Fox JG. Phylogeny of the defined murine microbiota: Altered Schaedler Flora. App Environ Microbiol 65: 3287-3292, 1999.

Batchelder MA, Bell JA, Erdman SE, Marini RP, Murphy JC, Fox JG. Pregnancy toxemia in the European ferret (Mustela putorius furo). Lab Anim Sci 49: 372-379, 1999.

Foley JE, Marks S, Munson L, Melli A, Dewhirst DE, Yu S, Shen Z, Fox JG. Isolation of Helicobacter canis from a colony Bengal cats with endemic diarrhea. J Clin Microbiol 37: 3271-3275, 1999.

Fox JG, Dangler CA, Taylor NS, King A, Koh T, Wang T. High salt diet induces gastric epithelial hyperplasia, parietal cell loss, and enhances Helicobacter pylori colonization in C57BL/6 mice. Cancer Research 59: 4823-4828, 1999.

Marini RP, Fox JG, Taylor NS, Yan L, McColm A, Williamson R. Ranitidine bismuth citrate and clarithromycin alone or in combination, for eradication of Helicobacter mustelae infection in ferrets. Am J Vet Res 60: 1280-1286, 1999.

McCathey S, Shomer NH, Schrenzel MD, Whary MT, Taylor NS, JG Fox. Colonization and tissue tropism of Helicobacter pylori and a novel urease-negative intestinal Helicobacter in ICR mice are independent of route of exposure. Helicobacter 4: 249-259, 1999.

Wang TC, Dangler CA, Chen D, Goldenring JR, Koh T, Raychowdhury R, Coffey RJ, Ito S, Varro A, GJ Dockray, Fox JG. Synergistic interaction between hypergastrinemia and helicobacter infection in a mouse model of gastric cancer. Gastroenterology 118: 36-47, 2000.

Esteves MI, Schrenzel MD, Marini RP, Taylor NS, Xu S, Hagen S, Feng Y, Shen Z, Fox JG. Helicobacter pylori gastritis in cats with long term natural infection as a model of human disease. Am J Pathol 156: 709-721, 2000.

Whary MT, Cline JH, King AE, Corcoran CA, Xu Shilu, Fox JG. Containment of Helicobacter hepaticus by use of husbandry practices. Comp Med 50: 78-81, 2000.

Young VB, Dangler CA, Fox JG, Schauer DB. Chronic atrophic gastritis in SCID mice experimentally infected with Campylobacter fetus. Infect Immun 68:2110-2118, 2000.

Fox JG, Beck P, Dangler CA, Whary MT, Wang TC, Shi HN, Nagler-Anderson, C. Concurrent enteric helminth infection modulates inflammation and gastric immune response and reduces Helicobacter-induced gastric atrophy. Nat Med 6: 536-542, 2000.

Fox JG, Dangler CA, Snyder SB, Richard MJ, Thilsted JP. C-cell (medullary thyroid carcinoma) associated with multiple endocrine neoplasms in a ferret (Mustela putorius). Vet Pathol 37: 278-282, 2000.

Chien CC, Taylor NS, Ge Z, Schauer DB, Young VB, Fox JG. Identification of cdtB homologues and cytolethal distending toxin activity in enterohepatic Helicobacter spp. J Med Micro 49: 525-534, 2000.

Fox JG, Chien CC, Dewhirst FE, Paster BJ, Shen Z, Melito PL, Woodward DL, Rodgers. FG. Helicobacter canadensis sp. nov. isolated from humans with diarrhea as an example of an emerging pathogen. J Clin Microbiol 38: 2546-2549, 2000.

Young VB, Chien CC, Taylor NS, Knox KA, Schauer DB, Fox JG. Cytolethal distending toxin in avian and human isolates of Helicobacter pullorum. J. Infect Dis 182:620-623, 2000.

Shen Z, Feng Y, Fox JG. Identification of enterohepatic Helicobacter species by restriction fragment length polymorphism analysis of the 16S rRNA gene. Helicobacter 5: 121-128, 2000.

Patterson MM, Schrenzel MD, Feng Y, Xu S, Dewhirst FE, Paster BJ, Thibodeau SA, Versalovic J, Fox JG. Helicobacter aurati sp. nov., a urease-positive Helicobacter species cultured from gastrointestinal tissues of Syrian hamsters. J Clin Microbiol 38: 3722-3728, 2000.

Whary MT, Cline JH, King AE, Hewes KM, Chojnacky D, Salvarrey A, Fox JG. Monitoring sentinel mice for Helicobacter hepaticus, H. rodentium and H. bilis infection by PCR and serology. Comp Med 50: 436-443, 2000.

Patterson MM, Schrenzel MD, Feng Y, Fox JG. Gastritis and intestinal metaplasia in syrian hamsters infected with Helicobacter aurati and two other microaerobes. Vet Pathol 37: 589-596, 2000.

Dial EJ, Hall LR, Romero JJ, Lechago J, Fox JG, Lichtenberger LM. Altered gastrin regulation in mice infected with Helicobacter felis. Dig Dis Sci 45: 1308-1314, 2000.

Dewhirst FD, Fox JG, Mendes EN, Paster BJ, Gates CE, Kirkbride CA, Eaton KA. Flexispira rappini strains represent at least ten Helicobacter taxa. Int J Syst Evol Microbiol 50: 1781-1787, 2000.

Ge Z, Feng Y, Dangler CA, Xu S, Tayor NS, Fox JG. Fumarate reductase is essential for Helicobacter pylori colonization of the mouse stomach. Microbial Pathogenesis 29: 279-287, 2000.

Kwon H, Pena JA, Osato MS, Fox JG, Graham DY, Versalovic J. Frameshift mutations in rdxA and metronidazole resistance in North American Helicobacter isolates. J Antimicrobiol Chemother 46: 793-796, 2000.

Harper CMG, Dangler CA, Xu S, Feng Y, ShenZ, Sheppard BJ, Stamper A, Dewhirst, FE, Paster BJ, Fox JG. Isolation and characterization of Helicobacter sp. from the gastric mucosa of dolphins, Lagenorhynchus acutus and Delphinus delphis. App Environ Microbiol 66: 4751-4757, 2000.

Bergin IL, Chien CC, Marini RP, Fox JG. Isolation and characterization of Corynebacterium ulcerans from cephalic implants in rhesus macaques (Macaca mulatta). Comp Med 50: 530-535, 2000.

Kwiecien JM, Blanco M, Fox JG, Delaney KH, Fletch AL. Neuropathology of bouncer long evans, a novel dysmyelinated rat. Comp Med 50: 503-510, 2000.

Fox JG, Wang TC. The ‘African enigma’-another explanation (letter). Nat Med 6: 1297-1298, 2000.

Chin EY, Dangler CA, Fox JG, Schauer DB. Helicobacter hepaticus infection triggers inflammatory bowel disease in T cell receptor ab mutant mice. Comp Med 50: 586-592, 2000.

Astrofsky KM, Schrenzel MD, Bullis RA, Smolowitz RM, Fox JG. Diagnosis and management of atypical Mycobacterium spp. infections in established laboratory zebrafish (Brachydanio rerio) facilities. Comp Med 50: 660-672, 2000.

Dewhirst FE, Fox JG, On SLW. Recommended minimal standards for describing new species of the genus Helicobacter. Int J Syst Evol Bacteriol 50: 2231-2237, 2000.

Gasbarrini A, Fox JG, Gasbarrini G. Helicobacter pylori and other Helicobacter spp. chronic infections and extragastric diseases. European J of Gastroenterol and Hepatol 12: 1057-1060, 2000.

Fox JG, Marini RP. Helicobacter mustelae infection in ferrets: Pathogenesis, epizootiology, diagnosis and treatment. Sem in Avian and Exotic Pet Med 10: 36-44, 2001.

Erdman SE, Fox JG, Dangler CA, Feldman D, Horwitz B. Cutting edge: typhlocolitis in NF-kB deficient mice. J Immunol 66: 1443-1447, 2001.

Simpson KW, Strauss-Ayali D, Straubinger RK, Scanziani E, McDonough PL, Straubinger AF, Chang YF, Esteves MI, Fox JG, Domeneghini C, Arebi N, Calam J. Helicobacter pylori infection in the cats: evaluation of gastric colonization, inflammation and function. Helicobacter 6: 1-14, 2001.

Fox JG, Handt L, Sheppard BJ, Xu S, Dewhirst FE, Motzel S, Klein H. Isolation of Helicobacter cinaedi from the colon, liver and mesenteric lymph node of a rhesus monkey with chronic colitis and hepatitis. J Clin Microbiol 39: 1580-1585, 2001.

Ge Z, Doig P, Fox JG. Characterization of proteins in the outer membrane preparation of a murine pathogen, Helicobacter bilis. Infect Immun 69: 3502-3506, 2001.

Peña JA, Fox JG, Ferraro MJ, Versalovic J. Molecular resistance testing of Helicobacter pylori in gastric biopsies. Arch Pathol Lab Med 125:493-497, 2001.

Fox JG, Handt L, Xu S, Shen Z, Dewhirst FE, Paster BJ, Dangler CA, Lodge K, Motzel S, Klein H. Novel Helicobacter species isolated from rhesus monkeys with chronic idiopathic colitis. J. Med Microbiol 50: 421-429, 2001.

Ihrig M, Dangler CA, Fox JG. Mice lacking inducible nitric oxide synthase develop spontaneous hypercholesterolaemia and aortic atheromas. Atherosclerosis 156: 103-107, 2001.

Shomer NH, Dangler CA, Schrenzel MD, Whary MT, Xu S, Feng Y, Paster BJ, Dewhirst FE, Fox JG. Cholangiohepatitis and inflammatory bowel disease (IBD) induced by a novel urease-negative Helicobacter species in A/J and Tac:ICR:Hascid mice. Biol & Exp Med 226: 420-428, 2001.

Fox JG. Human diseases associated with non-H. pylori helicobacters. Helicobacter Res 5: 35-44, 2001.

Shen Z, Feng Y, Dewhirst FE, Fox JG. Coinfection with enteric Helicobacter spp. and Campylobacter spp. in cats. J Clin Microbiol 39: 2166-2172, 2001.
Fox JG, Wang TC, Nagler-Anderson C. The African enigma: the parasite’s perspective (letter). Gut 48: 156-157, 2001.

Garcia A, Erdman SE, Sheppard BJ, Murphy JC, Fox JG. Gastric dilatation syndrome associated with chronic nephropathy hypergastrinemia, and gastritis in mice exposed to high levels of environmental antigens. Comp Med 51: 262-267, 2001.

Ge Z, White DA, Whary MT, Fox JG. Fluorogenic PCR-based quantitative detection of a murine pathogen Helicobacter hepaticus J Clin Microbiol 39:2598-2602, 2001.

Newman JV, Kosaka T, Sheppard BJ, Fox JG, Schauer DB. Bacterial infection promotes colon tumorigenesis in Apc Min/+ mice. J Infect Dis 184: 227-230, 2001.

Dykstra MJ, Astrofsky KM, Schrenzel MD, Fox JG, Bullis RA, Farrington S, Sigler L, Rinaldi MG, McGinnis MR. High mortalities in a large scale zebrafish colony (Brachydanio rerio Hamilton & Buchanan, 1822) associated with Lecythophora mutablis (van Beyma) W. Gams & McGinnis. Comp Med 51: 361-368, 2001.

Fox JG, Schauer DB, Wadstrom T. Enterohepatic Helicobacter spp. Current Opinion in Gastroenterol (suppl 1) 17: S28-S31, 2001.

Fox JG, Wang TC. Helicobacter pylori is a bad bug after all (editorial). N Engl J Med 345: 829-832, 2001.

Fox JG. Isolation of a Helicobacter strain from the human liver (letter). Gastroenterol 121: 1023-1024, 2001.

Ge Z, Feng Y, White D, Schauer DB, Fox JG. Genomic characterization of Helicobacter hepaticus: ordered cosmid library and comparative sequence analysis. FEMS Microbiol Lett 204: 147-153, 2001.

Franklin CL, Gorelick PL, Riley LK, Dewhirst FE, Livingston RS, Ward JM, Beckwith CS, Fox JG. Helicobacter typhlonius sp. nov., a novel murine urease-negative Helicobacter species. J Clin Microbiol 39: 3920-3926, 2001.

Whary MT, Cline J, King A, Ge Z, Shen Z, Sheppard B, Fox JG. Long term colonization levels of Helicobacter hepaticus in the cecum of hepatitis-prone A/JCr mice are significantly lower than those in hepatitis-resistant C57BL/6 mice. Comp Med 51:413-417, 2001.

Falush D, Kraft C, Taylor NS, Correa P, Fox JG, Achtman M, Suerbaum S. Recombination and mutation during long-term gastric colonization by Helicobacter pylori: estimates of clock rates, recombination size and minimal age. Proc Natl Acad Sci 98: 15056-15061, 2001.

Fox JG. The non- H. pylori helicobacters: Their expanding role in gastrointestinal and systemic diseases. Gut 50: 273-283, 2002.
Garcia A, Erdman SE, Feng Y, Rogers AB, Schrenzel MD, Murphy JC, Fox JG. Hepatobilary inflammation, neoplasia, and argyrophilic bacteria in a ferret colony. Vet Pathol 39: 173-179, 2002.

Astrofsky KM, Harper CM, Rogers AB, Fox JG. Diagnostic techniques for clinical investigation of laboratory zebrafish. Lab Anim 31: 41-45, 2002.
Fox JG, Wang TC. Helicobacter pylori infection: pathogenesis. Current Opinion in Gastroenterol 18: 15-25, 2002.

Fox JG, Sheppard BJ, Dangler CA, Whary MT, Ihrig M, Wang TC. Germline p53 mutation inhibits Helicobacter-induced premalignant lesions and invasive gastric carcinoma through downregulation of Th1 proinflammatory responses. Can Res 62:696-702, 2002.

Suerbaum S, Kraft C, Dewhirst FE, Fox JG. Helicobacter nemestrinae ATCC 49396T is a strain of Helicobacter pylori. Int J Syst Evol Microbiol 52:437-439, 2002.

Harper CMG, Xu S, Feng Y, Dunn JL, Taylor NS, Dewhirst FE, Fox JG. Identification of novel Helicobacter spp. from beluga whale. Appl Environ Microbiol 68:2040-2043, 2002.

Pena JA, McNeil K, Fox JG, Versalovic J. Molecular evidence of Helicobacter cinaedi-organisms in human gastric biopsy specimens. J Clin Microbiol 40:1511-1513, 2002.

Houghton J, Fox JG, Wang TC. Helicobacter pylori and other causes of gastric ulceration. Gastric cancer-Lab bench to clinic. J Gastroenterol Hepatol: 17: 495-502, 2002.

Fox JG. Other helicobacters involved in human diseases. Acta Gastroenterologica Belgica 65: 24-31-2002.

Fox JG, Xu S, Shen Z, Feng Y, Dangler CA, Dewhirst FE, Paster BJ, Cullen JM. Helicobacter marmotae sp. nov. isolated from livers of woodchucks and intestines of cats J. Clin Microbiol 40: 2513-2519, 2002.

Astrofsky KM, Schech JM, Sheppard BJ, Obenschain CA, Chin AM, Kacergis MC, Laver ER, Bartholomew JL, Fox JG. High mortality due to Tetrahymena sp. infection in laboratory maintained zebrafish (Brachydanio rerio). Comparative Medicine 52: 363-367, 2002.

Matsukura N, Yokomuro S, Yamada S, Tajiri T, Takashi T, Sundo T, Hadama T, Kamiya S, Fox JG. Association between Helicobacter bilis in bile and biliary tract malignancies: H. bilis in bile from Japanese and Thai patients with benign and malignant diseases in the biliary tract. Japanese J Can Res 93: 842-847, 2002.

Astrofsky KM, Roux MM, Klimpel KR, Fox JG, Dhar AK. Isolation of differentially expressed genes from white spot virus (WSV) infected Pacific blue shrimp (Penaeus stylirostris). Arch Virol 147: 1799-1812, 2002.

Harper C, Feng Y, Xu S, Taylor NS, Kinsel M, Dewhirst FE, Paster B, Greenwell M, Levine G, Rogers A, Fox JG. Helicobacter cetorum sp. nov., a urease positive Helicobacter species isolated dolphins and whales. J Clin Microbiol 40: 4536-4543, 2002.

Garcia A, Marini RP, Feng Y, Vitsky A, Taylor NS, Schauer DB, Fox JG. A naturally occurring rabbit model of enterohemorrhagic Escherichia coli-induced disease. J Infect Dis 186:1682-1686,2002.

Erdman SE, Poutahidis T, Rogers AB, Tomczak M,Cormier K, Horwitz BH, Fox JG. CD4+ CD45Rblo regulatory T lymphocytes inhibit microbially-induced colon cancer in Rag2-deficient mice. Am J Path 162: 691-702, 2003.

Todorova MT, Dangler CA, Drage MG, Sheppard BJ, Fox JG, Seyfried TN. Sexual dysfunction and sudden death in epileptic male EL mice: inheritance and prevention with the ketogenic diet. Epilepsia 44: 25-31, 2003

Fox JG, Rogers AB, Ihrig M, Taylor NS, Whary MT, Dockray G, Varro A, Wang TC. Helicobacter pylori associated gastric cancer in INS-GAS mice is gender-specific Cancer Res 63: 942-950, 2003.

Bergin IL, Sheppard BS, Fox JG. Helicobacter pylori infection and high dietary salt independently induce atrophic gastritis and intestinal metaplasia in outbred US bred Mongolian gerbils. Dig Dis Sci 48: 475-485, 2003.

Patterson MM, O’Toole PW, Forester N, Noonan B, Trust TJ, Xu S, Taylor NS, Marini RP Fox JG. Failure of surface ring-mutant strains of Helicobacter mustelae to persistently infect the ferret stomach. Infect Immun 71: 2350-2355, 2003

Fox JG, Wang TC, Rogers AB, Taylor NS, Dangler CA, Ge Z, Israel DA, Krishna U, Gaus K, Peek, RM. Host and microbial determinants influence Helicobacter pylori-induced gastric carcinogenesis in murine model of hypergastrinemia. Gastroenterology 124: 1879-1890, 2003.

Patterson MM, Rogers AB, Schrenzel MD, Marini RP, Fox JG. Alopecia attributed to neoplastic ovarian tissue in two ferrets Comp Med 53: 213-217, 2003

Shomer NH, Fox JG, Juedes A, Ruddle NH. Helicobacter-induced chronic active lympoid aggregates have characteristics of tertiary lymphoid tissue. Infect Immun 71: 3572-3577, 2003.

Schwarz L, Solano M, Manning A, Marini RP, Fox JG. The normal upper gastrointestinal examination in the ferret. J Vet Radiol 44: 165-172, 2003.

Suerbaum S, Josenhans C, Sterzenbach T, Bell M, Brandt P, Chevreux B, Drescher B, Droege M, Fartmann B, Fischer HP, Ge Z, Shen Z, Hörster A, Holland R, Mendz G, Macko L, Nyakatura G, Paquette J, Schauer D, Weber J, Frosch M, Fox JG. The complete genome sequence of the carcinogenic bacterium Helicobacter hepaticus. Proc Natl Acad Sci 100: 7901-7906, 2003.

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