James B. Kaper
Microbiology and Immunology
Biochemistry and Molecular Biology, Medicine
|Administrative Title: Chair, Department Of Microbiology & Immunology
Senior Associate Dean for Academic Affairs
I received my Ph.D. in Microbiology from the University of Maryland College Park (UMCP) in 1979 under the mentorship of Dr. Rita Colwell. My doctoral research concerned enteric bacterial pathogens in the Chesapeake Bay. From 1979 – 1981 I was a Postdoctoral Fellow with Dr. Stanley Falkow at the University of Washington in Seattle, where I worked on the molecular pathogenesis of Vibrio and Pseudomonas infections and developed techniques to study the molecular epidemiology of bacterial infections. In 1981, I joined the faculty of the University of Maryland School of Medicine as Chief of the Bacterial Genetics Section of the Center for Vaccine Development with academic appointments as Assistant Professor of Medicine (primary) and Microbiology & Immunology (secondary). In 1999, my primary academic appointment switched to the Department of Microbiology & Immunology, and in 2007 I became Chair of that Department. My research has been continuously funded by the NIH since 1982, including a MERIT award from the NIAID.
Research in my laboratory focuses on the molecular pathogenesis of enteric bacterial pathogens. Our studies range from basic research on pathogenesis and prokaryotic gene regulation to translational research such as the development of new vaccines and diagnostic probes. The specific pathogens being studied are Vibrio cholerae and diarrheagenic Escherichia coli. Our work with V. cholerae has resulted in the development of an attenuated live oral cholera vaccine that was the first recombinant bacterial vaccine to be tested in and licensed for humans. We are currently investigating the interaction of V. cholerae and the innate immune system, specifically the activation of TLR5 by V. cholerae flagella, and the in vivo induction of gene expression during infection. Our work with pathogenic E. coli focuses on enteropathogenic E. coli (EPEC), a cause of infant diarrhea, and enterohemorrhagic E. coli O157:H7 (EHEC), a cause of bloody diarrhea and hemolytic uremic syndrome. The latter pathogen has achieved particular notoriety as the cause of large outbreaks of disease due to ingestion of contaminated spinach and hamburgers. Our research has yielded many insights into the pathogenesis and evolution of these pathogens, including the discovery of a 35,000 bp “pathogenicity island” that mediates epithelial cell adherence and intestinal histopathology, global regulators of virulence gene transcription, a cell-to-cell signaling system (quorum sensing) that regulates virulence gene expression, and diagnostic DNA probes.
Schuller, S., R. Heuschkel, F. Torrente, J.B. Kaper, and A.D. Phillips. Shiga toxin binding in normal and inflamed human intestinal mucosa. Microbes and Infection, 2007, 9:35-39.
Zhu, C., S. Feng, Z. Yang, K. Davis, H. Rios, J.B. Kaper, and E.C. Boedeker. LEE-encoded regulator (Ler) mutants elicit serotype-specific protection, but not cross-protection, against attaching and effacing Escherichia coli strains. Vaccine, 2007, 25:1884-1892.
Rendón, M.A., Z. Saldana, V. Monteiro-Neto, A.L. Erdem, D.R. Hernández, A. Vázquez, J.B. Kaper, J.L. Puente, and J.A. Girón. Commensal and pathogenic Escherichia coli use a common pilus adherence factor for epithelial cell colonization. Proceedings of the National Academy of Sciences, USA, 2007, 104:10637-10642.
Xicohténcatl-Cortes, J., V. Monteiro-Neto, M.A. Rendón, M.A. Ledesma, O. Francetic, P. Samadder, P. Vázquez, J.B. Kaper, J.L. Puente, J.A. Girón. Intestinal Adherance associated with type IV pili of Enterohemorrhagic Escherichia coli O157:H7. Journal of Clinical Investigation, 2007 Nov 1; 117 (11): 3519-3529.
Lombardo, M-J, J. Michalski, H. Martinez-Wilson, N. Maroncle, C.G. Osorio, J.P. Nataro, C.O. Tacket, A. Camilli, and J.B. Kaper. A V. cholerae IVET (In Vivo Expression Technology) screen in human volunteers. Proceedings of the National Academy of Sciences, USA PNAS, 2007, 104:18229-18234
Zhu, C., S. Feng, V. Sperandio, Z. Yang, T.E. Thate, J.B. Kaper, E.C. Boedeker. The possible influence of LuxS in the in vivo virulence of rabbit enteropathogenic Escherichia coli. Veterinary Microbiology, 2007, 125: 313-322.
Gomez-Duarte O.G., Chattopadyay S., Weissman S.J., Giron J.A., Kaper, J.B., Sokuremko E.V., Genetic Diversity of the gene cluster encoding Longus, a type IV pilus of enterotoxigenic Escherichia coli. Journal of Bacteriology, 2007, 189:9145-9149
Bai L., Schuller S., Whale, Mousiner A., Marches O., Wang L., Ooka T., Heushkel R. Torrente F., Kaper J.B., Gomes T.A.,Xu J., Phillips A.D., Frankel G., Enteropathogenic Escherichia coli O125:H6 triggers attaching and effacing lesions on human biopsy specimens independently of Nck and TccP/TccP2. Infection and Immunity, 2008, 76:361-368
Kaper, J.B. and M.A. Karmali. The continuing evolution of a bacterial pathogen. Proceedings of the National Academy of Sciences, USA, 2008 105:4543-4536
Harrison, L.M., P. Rallabhandi, J. Michalski, X. Zhou, S.R. Steyert, S. N. Vogel and J. B. Kaper. Vibrio cholerae flagellins induce Toll-like receptor 5-mediated interleukin-production through mitogen-activated protein kinase and NF-kappaB activation. Infection and Immunity, 2008, 76:5524-5534. PMC 2583592
Lodato, P. B. and J. B. Kaper. Post-transcriptional processing of the LEE4 operon in enterohaemorrhagic Escherichia coli. Molecular Microbiology, 2009, 71:273-290.PMC 2782684
Schüller, S., M. Lucas, J. B. Kaper, J. A. Girón and A. D. The ex vivo response of human intestinal mucosa to enteropathogenic Escherichia coli infection. Cellular Microbiology, 2009, 11:521-30. PMC 2676445
Saldaña, Z, J. Xicohtencatl-Cortes, F. Avelino, A. D. Phillips, J. B. Kaper, J. L. Puente, and J. A. Girón. Synergistic role of curli and cellulose in cell adherence and biofilm frmation of attaching and effacing Escherichia coli and identification of Fis as a negative regulator of curli. Environmental Microbiology, 2009, 11:992-1006. PMC 2672964
Samadder, P., J. Xicohtencatl-Cortes, Z. Saldaña Z, D. Jordan, P. I. Tarr, J. B. Kaper, and J. A. Girón. The Escherichia coli ycbQRST operon encodes fimbriae withlaminin-binding and epithelial cell adherence propterties in Shiga-toxigenic Escherichia coli O157:H7. Environmental Microbiology, 2009, 11:1815-1826. PMC 2888687
Saldaña, Z., A. L. Erdem, S. Schüller, I. N. Okeke, M. Lucas, A. Sivananthan, A. D. Phillips, J. B. Kaper, J. L. Puente, and J. A. Girón. The Escherichia coli common pilus and the bundle-forming pilus act in concert during the formation of localized adherence by enteropathogenic E. coli. Journal of Bacteriology, 2009, 191:3451-3461. PMC 2681888
Hansen, A. M., and J. B. Kaper. Hfq affects the expression of the LEE pathogenicity sland in enterohaemorrhagic Escherichia coli. Molecular Microbiology, 2009, 73:446- 465. PMC 2770234
Morin, C. E. and J. B. Kaper. Use of stabilized luciferase-expressing plasmids to examine in vivo-induced promoters in the Vibrio cholerae vaccine strain CVD 103-HgR, FEMS Immunology & Medical Microbiology, 2009, 57:69-79. PMC 2906245
Keller, R., T.D. Hilton, H. Rios, E.C. Boedeker, and J.B. Kaper. Development of a live oral attaching and effacing Escherichia coli vaccine candidate using Vibrio cholerae CVD103-HgR as antigen vector. Microbial Pathogenesis, 2010, 48:1-8. PMC 2814881
Caburlotto, G., M. M. Lleò, T. Hilton, A. Huq, R. R. Colwell and J. B. Kaper. Effect on human cells of environmental Vibrio parahaemolyticus strains carrying type III scretion system 2. Infection and Immunity, 2010, 78:3280-7. PMC 897368
Newton, H.J, J. S. Pearson, L. Badea, M. Kelly, M. Lucas, G. Holloway, K. M. Wagstaff, M. A. Dunstone, J. Sloan, J. C. Whisstock, J. B. Kaper, R. M. Robins-Browne, D. A. Jans, G. Frankel, A. D. Phillips, B. S. Coulson, and E. L. Hartland. The type III effectors NleE and NleB from enteropathogenic E. coli and OspZ from Shigella block nuclear translocation of NF-κB p65. PLoS Pathogens, 2010, 13;6:e1000898. PMC 2869321
Habdas, B. J., J. Smart, J. B. Kaper, V. Sperandio. The LysR-type transcriptional regulator QseD alters type three secretion in enterohemorrhagic Escherichia coli and motility in K-12 Escherichia coli. Journal of Bacteriology, 2010, 192:3699-712. PMC 2897335
Steyert, S. R., D. A. Rasko and J. B. Kaper. Functional and phylogenetic analysis of ureD in Shiga toxin-producing Escherichia coli. Journal of Bacteriology, 2011, 193:875-886. PMC3028682
Rhee, K. J., H. Cheng, A. Harris, C. Morin, J. B. Kaper, and G. Hecht. Determination of spatial and temporal colonization of enteropathogenic E. coli and enterohemorhagic E. coli in mice using bioluminescent in vivo imaging. Gut Microbes, 2011, 2;34-41
Torres. A. G., R.J. Cieza, M. Rojas-Lopez, C.A. Blumentritt, C.S. Souza, R.K. Johnston, N. Strockbine, J. B. Kaper, E. Sbrana and V. Popov. In vivo bioluminescence imaging of E. coli O104:H4 and characterization of virulence propertiesin a mouse model of infection. BMC Microbiology, 2012, 12:112.
Steyert, S.R. and J. B. Kaper. Contribution of Urease to the Pathogenicity of Shiga Toxin-Producing Escherichia coli. Infection and Immunity, 2012, 80:2589-600.
Lodato, P.B., P-K. Hsieh, J. G. Belasco, and J. B. Kaper. A mini-ORF in the leader region protects a T3SS mRNA from degradation by RNase E. Molecular Microbiology, 2012, 86:1167-82.
Faherty, C., J. M. Harper, T. Shea-Donohue, E. M. Barry, J. B. Kaper, A. Fasano, and J. P. Nataro. Chromosomal and plasmid-encoded factors of Shigella flexneri induce secretogenic activity ex vivo. PLoS One, 2012, 7:e49980.
Hansen, A-M., Chaerkady, R., J. Sharma, J. J. Diazmejia, N. Tyagi, S. Renuse, H. K.C. Jacob, S. M. Pinto, N. A. Sahasrabuddhe, M-S. Kim, B. Delanghe, N. Srinivasan, A. Emili, J. B. Kaper, and A. Pande. The Escherichia coli phosphotyrosine proteome relates to core pathways and virulence. PLoS Pathogens, 2013, in press.