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James B. Kaper, PhD

James & Carolyn Frenkil Distinguished Dean’s Professor, Vice Dean for Academic Affairs, and Chair, Department of Microbiology & Immunology

Academic Title:

Professor

Primary Appointment:

Microbiology and Immunology

Secondary Appointment(s):

Medicine, BioChemistry&Molecular Biology

Administrative Title:

Chair, Department of Microbiology & Immunology; Vice Dean for Academic Affairs

Location:

HSF1, 380

Phone (Primary):

(410) 706-7114

Phone (Secondary):

(410) 706-2344

Fax:

(410) 706-6970

Education and Training

  • University of Maryland, BS, Microbiology, 1973
  • University of Maryland, PhD, Microbiology, 1979
  • University of Washington, Post-doctoral Study, Molecular Pathogenesis, 1979

Biosketch

Dr. Kaper is an internationally-recognized microbiologist with specific expertise in the molecular pathogenesis of diarrheal disease pathogens, specifically Vibrio cholerae and diarrheagenic Escherichia coli. He has constructed a number of live attenuated V. cholerae vaccine strains, which his long-time collaborator, Dr. Myron Levine, tested in numerous volunteer and field trials for clinical safety and efficacy.

These strains included the first genetically engineered bacterial vaccine to be tested in humans (attenuated V. cholerae strain JBK70) and the first recombinant bacterial vaccine licensed for human use (attenuated V. cholerae strain CVD 103-HgR). Funded since 1982 by the National Institute of Allergy and Infectious Diseases, Dr. Kaper’s research on the pathogenesis of enteric disease has contributed to six books, 68 book chapters, and 303 articles published in peer-reviewed journals.

As chair of the Department of Microbiology & Immunology at the UMSOM, he has trained more than 60 graduate students and postdoctoral fellows in the area of enteric pathogenesis, many of whom now hold leadership positions in preeminent academic institutions. In addition to his roles as scientist and department chair, Dr. Kaper is also an academic leader in the School of Medicine, serving as Senior Associate Dean for Academic Affairs, where he oversees all of the School’s academic programs.

Research/Clinical Keywords

Microbiology, Immunology, Bacterial Vaccines, Enteric Pathogenesis, Bacterial Genetics, Intestinal Colonization

Highlighted Publications

Kaper, J.B., H. Lockman, M.M. Baldini, and M.M. Levine.  Recombinant nontoxinogenic Vibrio cholerae strains as attenuated cholera vaccine candidates. Nature, 1984; 308:655 658.

Kaper, J.B., H.B. Bradford, N.C. Roberts, and S. Falkow.  Molecular epidemiology of Vibrio cholerae resident in the U.S. Gulf Coast.  Journal of Clinical Microbiology, 1982; 16:129 134.

Trucksis, M., J. Michalski, Y. Kang Deng, and J.B. Kaper.  The Vibrio cholerae genome contains two unique circular chromosomes. Proceedings of the National Academy of Sciences, USA, 1998, 95:14464 14469.

Sperandio, V., J.L. Mellies, W. Nguyen, S. Shin, and J.B. Kaper.  Quorum sensing controls expression of the type III secretion gene transcription and protein secretion in enterohemorrhagic and enteropathogenic Escherichia coli. Proceedings of the National Academy of Sciences, USA, 1999, 96: 15196-15201

Sperandio, V., A.G. Torres, B. Jarvis, J.P. Nataro, and J.B. Kaper.  Bacteria-host communication: the language of hormones. Proceedings of the National Academy of Sciences, USA, 2003, 100:8951-8956 PMC 166419

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, 9(6):e1003403 PMCID: 3681748

Additional Publication Citations

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.

Research Interests

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.

Awards and Affiliations

  • Elected Fellow, American Academy of Microbiology, 1994
  • Elected Fellow, American Association for the Advancement of Science, 1994
  • Associate Editor, International Journal of Medical Microbiology, 2000 – present
  • Merit Award, National Institutes of Health, 2004
  • Editor-in-Chief, EcoSal: Escherichia coli and Salmonella Cellular & Molecular Biology, 2006 – present
  • Associate Editor, Gut Microbes, 2009 – present
  • Elected to Pass & Susel Academy of Educational Excellence, University of Maryland School of Medicine, 2010
  • ASM DC White Award for Interdisciplinary Research & Mentoring in Microbiology, American Society for Microbiology, 2019
  • James and Carolyn Frenkil Distinguished Dean's Professorship, 2019

Links of Interest

Previous Positions

  • Graduate teaching and Research Assistant, Department of Microbiology, University of Maryland, College Park, Maryland, 1975 – 1979
  • Senior Fellow, Department of Microbiology, University of Washington, Seattle, Washington, 1979 – 1981
  • Assistant Professor of Microbiology and of Medicine, University of Maryland, Baltimore, 1981 – 1984
  • Chief, Bacterial Genetics Section, Center for Vaccine Development, University of Maryland School of Medicine, Baltimore, 1981 – present
  • Associate Professor of Medicine, Microbiology and Biological Chemistry, University of Maryland School of Medicine, Baltimore, Maryland, 1984 – 1990
  • Professor of Medicine (primary appointment), Microbiology and Immunology, Biological Chemistry, University of Maryland School of Medicine, Baltimore, 1990 – 1998
  • Professor of Microbiology and Immunology (primary appt.), Biological Chemistry, and Medicine, University of Maryland School of Medicine, Baltimore, 1998 – present
  • Chair, Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, 2007 – present
  • Senior Associate Dean for Academic Affairs, University of Maryland School of Medicine, Baltimore, 2014 – present

Patents

James B. Kaper and Myron M. Levine
"Method of Isolating Restriction Fragment Deletions in Vibrio cholerae, and Products Thereof"
U.S. Patents No. 4,935,364; 5,135,862; and 5,470,729

James B. Kaper and Myron M. Levine
"Vibrio cholerae strain CVD103HgR, Method of Making Same, and Vaccines Derived Therefrom"
U.S. Patents No. 5,399,494 and 5,628,994

James B. Kaper and Myron M. Levine
"Vibrio cholerae O1 (CVD111) and non‑O1 (CVD112 and CVD112RM) Serogroup Vaccine Strains, Methods of Making Same and Products Thereof"
U.S. Patent No. 5,882,653

James B. Kaper and Karen Jarvis
“Immunodiagnostic Test for Enterohemorrhagic Escherichia coli Infection”
U.S. Patent No. 6,204,004

James B. Kaper and Karen Jarvis
Escherichia coli secreted protein B”
U.S. Patent No. 6,635,259

Multiple international patents for cholera vaccines

Licensed Vaccines:

CVD 103-HgR, a recombinant live oral cholera vaccine
Licensed by the US FDA on June 10, 2016
Previously licensed in numerous countries including Argentina, Australia, Canada, Colombia, Guatemala, el Salvador, Finland, Honduras, Nicaragua, Norway, Peru, the Philippines, Sri Lanka, Sweden, Switzerland, Venezuela.