Stephanie Seveau, Ph.D. seveau.1@osu.edu Ph.D., Pierre and Marie Curie University, Paris, France Postdoctoral Training, Department of Biochemistry, Weill Medical College of Cornell University, NewYork, USA

Assistant Professor, Microbiology & Internal Medicine
Member, Center for Microbial Interface Biology

RESEARCH INTERESTS

Dr. Seveaus research is focused on understanding, at the molecular level, host-pathogen interactions and the host responses to bacterial toxins. The results of her research provide a molecular basis for the logical design of new anti-microbial therapeutics. Specific projects currently are to:

1. Establish how Listeria monocytogenes invades and establishes infections of mammalian cells and tissues. L. monocytogenes is a food-borne intracellular bacterial pathogen that causes gastroenteritis, meningitis, encephalitis and fetal infections of humans. L. monocytogenes lives inside host cells, and its ability to invade mammalian cells facilitates both its initial transit through the epithelial barrier of the digestive tract, and subsequent colonization of many internal organs. State-of-the-art quantitative fluorescence microscopy is used as the primary approach to investigate and quantify L. monocytogenes infections of live host cells. The complex dynamics of the signaling events that lead to L. monocytogenes uptake by epithelial cells and macrophages are being determined and characterized.

2. Determine the molecular basis, and outcome of host-cell signaling induced by cholesterol-dependent cytolysin (CDCs) toxins. CDCs are a family of closely-related pore-forming bacterial toxins produced by many Gram-positive Listeria, Streptococcus, Bacillus and Clostridium species. At concentrations below those that cause host-cell lysis, these virulence factors function as signaling molecules but the underlying molecular biology and the host cell responses to this toxin-signaling remain unknown. To gain this information, we are investigating the signaling properties of listeriolysin O, a CDC and the major virulence factor of L. monocytogenes. Structure-function dissection of listeriolysin O is being combined with live-cell imaging to establish how this toxin affects host-cell signaling during the course of a bacterial infection.

Haghighat AC, Seveau S. 2010. Quantification of host-microbes interactions by automated fluorescence microscopy. J Immunol Methods.  Jan 31;352(1-2):186-91.

Hoppe AD, Seveau S, Swanson JA. 2009. Live Cell fluorescence microscopy to study microbial pathogenesis. Review, Cell Microbio. 4:540-50.

Seveau, S., Tham, T.N., Payrastre, B., Hoppe, A.D., Swanson, J.A., and Cossart, P. 2007. A FRET analysis to unravel the role of cholesterol in Rac1 and PI 3-kinase activation in the InIB/Met signalling pathway. Cell Microbiol. 9:790-803.

Seveau, S., Pizzaro-Cerda, J., and Cossart, P. 2007.Molecular mechanisms exploited by Listeria monocytogenes during host cell invasion. Review. Microbes and Infection. 10:1167.

Hamon, M., Batsche, E., Muchardt, C., Nam, T.T., Seveau, S., and Cossart, P. 2007. Histone modifications induced by a family of bacterial toxins. PNAS. 33:13467.

Diakonova, M., Helfer, E., Seveau, S., Swanson, J.A., Kocks, C., Rui, L., Carlier, M., and Carter-Su, C. 2007. Adapter protein SH2-Bß stimulates Actin-based motility of Listeria monocytogenes in a VASP-dependent fashion. Infection and Immunity. 7:3581.

Martinez , J.J., Seveau, S., Veiga-Chacon, E., Matsuyama , S., and Cossart, P. 2005. Ku70, a component of DNA-dependent protein kinase, is a receptor involved in Rickettsia conorii invasion of mammalian cells. Cell 123 (6):1013-1023.

Seveau, S., Bierne, H., Giroux, S., Prevost, M.C., and Cossart, P. 2004. Role of lipid rafts in E-cadherin- and HGF-R/Met-mediated entry of Listeria monocytogenes into host cells. J. Cell Biol. 166:743-753.