Virginia L. Miller, Ph.D.

Washington University
School of Medicine

Dept. of Molecular Microbiology
Box 8230
660 S. Euclid Ave.
St. Louis, MO 63110

tel: (314) 286-2891
fax: (314) 286-2896
email: vlmiller@wustl.edu
web: Personal Weblink

 

 

RESEARCH INTEREST

Our laboratory has been has been using Yersinia and Salmonella as model systems to study bacterial pathogenesis. The long term goals are to understand the bacteria-host interaction at the molecular level to determine how this interaction affects the pathogenesis of infections and how these pathogens co-ordinate the expression of virulence determinants during an infection. To do this, the laboratory uses genetic, molecular and immunological approaches, and the mouse model of infection. Y. enterocolitica is an excellent model system for studying host-pathogen interactions and the genetic basis of virulence due to the relative ease of manipulation of the pathogen as well as the animal model of infection. Thus, a fuller analysis of the virulence genes of Y. enterocolitica and their contribution to pathogenesis should yield insights into yersiniosis and into how other gastrointestinal pathogens interact with the host to cause disease. Several genetic approaches have been applied to identify new virulence genes; studies are ongoing to characterize these genes, their products and their role in disease.

For Yersinia, this lab has also been studying the invasion gene inv. The goals of this work are to determine the role of Inv in virulence and to determine the mechanism of regulation of expression of inv. An inv regulatory gene, rovA, has been identified which regulates expression of inv during an infection. RovA also regulates expression of other novel virulence determinants that influence the early inflammatory response. The laboratory is continuing to characterize the rovA regulon and its role in the host-pathogen interaction. For Salmonella, we have been characterizing the transcriptional regulation of genes required for invasion and diarrhea. This regulation involves an unusual interaction between a DNA binding protein and a type III secretion system chaperone.

SELECTED PUBLICATIONS

Dube, P. H., S. A. Handley, J. Lewis, and V. L. Miller. Protective role of IL-6 during Y. enterocolitica infection is mediated through the modulation of inlfammatory cytokines. Infect. Immun. 2004; in press.

Handley SA, Dube PH, Revell PA, Miller VL Characterization of oral Yersinia enterocolitica infection in three different strains of inbred mice. Infect Immun. 2004; 72:1645-56.

Ellison DW, Young B, Nelson K, Miller VL. YmoA negatively regulates expression of invasin from Yersinia enterocolitica. J Bacteriol. 2003;185: 7153-9.

Dube PH, Handley SA, Revell PA, Miller VL. The rovA mutant of Yersinia enterocolitica displays differential degrees of virulence depending on the route of infection. Infect Immun. 2003; 71: 3512-20.

Dube PH, Revell PA, Chaplin DD, Lorenz RG, Miller VL. A role for IL-1 alpha in inducing pathologic inflammation during bacterial infection. Proc Natl Acad Sci U S A. 2001; 98: 10880-5.