John Leong, Ph.D.,M.D.

Academic Role: Professor

Faculty Appointment(s) In:
   Molecular Genetics and Microbiology

Other Affiliation(s):
   Bacterial Genetics and Pathogenesis
   Cell Dynamics Group
   Center for AIDS Research
   Interdisciplinary Graduate Program
   Program in Immunology and Virology

Interactions of pathogenic bacteria with mammalian cells.

Lyme disease and relapsing fever bacteria of the genus Borreliae are tick-borne spirochetes that cause multisystemic infection. We have sought to investigate the spirochetal factors that promote colonization, and components of the host immune response that contribute to spirochetal clearance. We are analyzing mutants of the Lyme disease spirochete that are incapable of recognizing mammalian cell receptors to determine how pathogen-host cell interactions promote disease. We are also utilizing the highly tractable murine infection model for relapsing fever to elucidate a novel mechanism of T cell-independent immunologic memory.

Enteropathogenic and enterohemorrhagic Escherichia coli O157:H7 are important intestinal pathogens that stimulate actin polymerization in the host cell directly beneath the bound bacterium. Upon initial attachment to intestinal epithelial cells, these pathogens inject into host cells effector proteins that directly stimulate mammalian proteins known to control actin assembly. We are studying the action of these proteins to understand how interactions between these bacteria and the intestinal epithelium promote colonization and disease, as well as to gain insight into fundamental mechanisms of actin assembly in mammalian cells.

Recent Publications

Campellone, K. G., Robbins, D., and Leong, J. M. (2004).  EspF_U, a translocated effector that interacts with Tir and N-WASP and promotes Nck-independent actin pedestal formation by enterohemorrhagic E. coli O157:H7.  Dev. Cell 7:217-28.

Alugupalli, K.R., Akira, S., Lien, E., and Leong, J.M. (2007). MyD88- and Btk-mediated signals are essential for T cell-independent pathogen-specific IgM responses. J Immunol. 178: 3740-49.

Brady, M.J., Campellone, K.G., Ghildiyal, M., and Leong, J.M.  (2007). Enterohemorrhagic and enteropathogenic E. coli Tir proteins trigger a common Nck-independent actin assembly pathway. Cellular Microbiol., 9:2242-53.

Ritchie, J.M., Brady, M.J., Riley, K.N., Ho, T.D., Campellone, K.G., Herman, I.M., Donohue-Rolfe, A., Tzipori, S., Waldor M.K., and Leong, J.M. (2007). EspF_U, a type III-translocated effector of actin assembly, fosters epithelial association and late-stage intestinal colonization by E. coli O157:H7. Cellular Microbiol., in press.

Rotation Projects

1.  Role of cell attachment in tissue colonization by the Lyme disease spirochete. Mice will be infected with mutants of the Lyme disease spirochete that are incapable of recognizing specific host molecules to identify the interactions that are critical for bacterial colonization.

2.  Role of a T-independent B cell response in the control of Lyme disease. Immunodeficient mice reconstituted with a specific subset of T-independent B cells will be challenged with the Lyme disease spirochete to determine what cellular components of the immune system contribute to immunity to Lyme disease.

3.  Reconstitution of EHEC O157:H7-mediated actin assembly in cell free extracts. Small particles coated with effector proteins of EHEC O157:H7 will be added to extracts from mammalian cells or Xenopus laevis (frog) eggs to reconstitute actin assembly in vitro.  The critical host molecules participating in this pathway will be identified.  

Academic Background

Ph.D. (1985) Brown University
M.D. (1987) Brown University

Office: S6-214
Phone: 508-856-4059
E-mail: John.Leong@umassmed.edu
Keywords: Microbial Pathogenesis, Organisms - vertebrate/human cell lines, Cytoskeleton, Infectious Disease, Organisms - microbes

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