Dr. Scidmore is an Associate Professor in the Department of Microbiology and Immunology and has been associated with the department since 2001. She received a bachelor degree in Molecular Biology from the University of California at San Diego in 1987 and a Ph. D. degree in Molecular Biology from Princeton University in 1993. Before joining the department of Microbiology and Immunology, she obtained post-doctoral training at Rocky Mountain Laboratories, studying the intracellular development of Chlamydia.
The major focus of my laboratory is the identification of the pathogenic mechanisms utilized by Chlamydia species to promote and maintain their intracellular survival. Chlamydiae are obligate intracellular bacteria that are the leading cause of both sexually transmitted disease and preventable blindness worldwide as well as a leading cause of disease in veterinary animals. Chlamydiae replicate within a non-acidified vacuole termed an inclusion, which is actively modified by the bacteria to prevent lysosomal fusion and promote intracellular survival. A large family of chlamydial proteins termed inclusion membrane proteins (Inc) that are specifically localized to the inclusion membrane has recently been identified. Based upon their intracellular localization, we propose that this unique family of Inc proteins facilitates multiple aspects of chlamydial pathogenesis including regulation of the vesicular trafficking properties of the inclusion, prevention of lysosomal fusion, nutrient acquisition, modulation of host signal transduction pathways, and the induction and modulation of host inflammatory responses through recruitment of host proteins to the inclusion.
We are probing the function of each Inc through the identification and characterization of their specific cellular targets. Toward this goal, the lab has recently identified a specific interaction between C. trachomatis IncG and mammalian 14-3-3?, a phosphoserine binding protein that regulates diverse signal transduction pathways through directed subcellular localization of signaling complexes. Experiments are ongoing to define the biologic function of 14-3-3's recruitment to the inclusion and to determine whether chlamydiae recruit 14-3-3 proteins to exploit and alter 14-3-3 dependent signaling pathways in infected cells.
Another related facet of the lab's research is directed at identifying
both the host and chlamydial factors that specifically regulate the intracellular
trafficking and the fusogenic properties of the chlamydial inclusion.
The inclusion is trafficked to the peri-Golgi region of the host cell
by processes that are dependent on early chlamydial gene expression. Recently,
the lab has demonstrated the specific recruitment of several Rab GTPases
(Rab1, 4, 6, 10, and 11) to chlamydial inclusions. Current research is
directed toward deciphering the role of each inclusion associated Rab
GTPase through the use of dominant interfering mutants and siRNA technology
as well as in identifying the proteins that recruit each Rab GTPase to
Dr. Scidmore is a member of the following Graduate Fields:
Andrew Moorehead, Graduate Student
Scidmore, M.A., Fischer, E.R., and Hackstadt, T. 1996. Sphingolipids and glycoproteins are differentially trafficked to the Chlamydia trachomatis inclusion. J. Cell Biol. 134:363-374.
Scidmore-Carlson, M.A., Shaw, E.I., Dooley, C.A., Fischer, E.R., and Hackstadt, T. 1999. Identification and characterization of an early Chlamydia trachomatis operon containing four novel inclusion membrane proteins. Mol. Microbiol. 33:753-765.
Scidmore, M.A. and Hackstadt, T. 2001. Mammalian 14-3-3b is localized to the Chlamydia trachomatis inclusion via its interaction with the C. trachomatis inclusion membrane protein IncG. Mol. Microbiol. 39:1638-1650.
Rzomp, K. A., Scholtes, L. D., Briggs, B. J., Whittaker, G. R. and Scidmore, M.A. 2003. Rab GTPases are recruited to chlamydial Inclusions in a species-dependent and species-independent manner. Infect. Immun. 71: 5855-5870.
Rzomp, K. A., Moorhead, A. R., and M.A. Scidmore. (2006.) The GTPase Rab4 interacts with Chlamydia trachomatis inclusion membrane protein CT229. Infect. Immun. 74:5362-5373.
Moorhead, A. R., Rzomp, K. A., and M. A. Scidmore. (2007). The Rab6 effector, BICD1, is recruited to C. trachomatis inclusions in a biovar-specific manner. Infect. Immun. 75: 781-791.