Justice, Sheryl

Sheryl Justice, Ph.D.
Principle Investigator
Justices@ccri.net                              
700 Children's Drive
Columbus, OH 43205
p: 614.722.2700 | f: 614.722.2818 
 
 
Education
2006      Postdoctoral Research Fellow      Microbial Pathogenesis      Washington University in St. Louis, St. Louis, MO

2001      Ph. D.      Molecular Biology and Biochemistry      University of Connecticut, School of Medicine, Farmington, CT

1994      M.S.      Biochemistry      University of Missouri-Kansas City, Kansas City, MO

Research Interests
More than 4.5 million women and children will seek treatment for a urinary tract infection (UTI), accounting for almost 2 billion dollars in medical expenditures each year.  Uropathogenic Escherichia coli (UPEC) is the most common causative agent, accounting for up to 80% of all reported cases. In addition to an increase in the number of antibiotic resistant organisms that cause UTI, clinicians are frustrated by the significant recurrence that occurs within the first year of presentation with a UTI.  Many women use antibiotics daily to reduce the rate of recurrence, only to succumb to infection upon discontinuing antibiotic treatment. UTIs have been classically described as self-limiting, extracellular infections that recur due to re-introduction of bacteria into the bladder.  This paradigm for UTIs has been challenged due to the mounting information obtained by investigations of murine cystitis using strains of UPEC isolated from the urine of women seeking treatment for cystitis.  Multiple studies have demonstrated that UPEC invades into the superficial bladder epithelial cells.  While free in the epithelial cell cytoplasm, UPEC growth proceeds through a complex developmental and differentiation pathway, leading to the establishment of a chronic, quiescent infection in the bladder tissue.  This chronic infection can be the source of organisms for a recurrent infection, demonstrating that current treatments need to be modified to aide in curing and/or preventing recurrent UTIs.  The innate immune response is primarily responsible for the control of infectious agents in the urinary tract.  UPEC has devised multiple strategies to combat these defenses to establish infection.  Initially, UPEC suppress the production of cytokines produced by bladder epithelial cells to recruit infiltration of neutrophils.  Secondly, residence in the intracellular environment allows for survival from innate immune-mediated killing.   Lastly, during this developmental cycle, filamentous UPEC are observed in hosts with an intact immune response to lipopolysaccharide (LPS), suggesting that bacteria and host recognize and respond to each other.  Real-time video microscopic evaluation of infected murine bladders revealed that filamentous UPEC may also play a role in evasion of the innate immune-mediated killing.  My laboratory will focus on characterization of the bacterial and host factors required for the UPEC developmental pathway, the mechanisms of innate immune evasion, in addition to deciphering the molecular signals produced by both host and pathogen that occur at the host-pathogen interface.  The ultimate goal is to use this information to rationally identify novel therapeutic regimens.  

Selected Publications
Justice SS, Lauer SR, Hultgren SJ, Hunstad DA. (2006) Maturation of intracellular Escherichia coli communities requires SurA Infection and Immunity Aug;74(8):4793-800. PubMed ID: 16861667

Justice SS, Hunstad DA, Seed PC, and Hultgren SJ. (2006) Filamentation by E. coli subverts innate defenses during urinary tract infections. Proceedings of the National Academy of Sciences USA, in press. PubMed ID: 17172451

Hunstad DA, Justice SS, Hung CS, Lauer SR, and Hultgren SJ (2005) Suppression of bladder epithelial cytokine responses by uropathogenic Escherichia coli. Infection and Immunity 73(7); 3999-4006. PubMed ID: 15972487

Justice SS, Hunstad DA, Reiss Harper J, Duguay A, Pinkner JS, Bann J, Frieden C, Silhavy TJ, and Hultgren SJ (2005) Periplasmic peptidyl prolyl cis-trans isomerases are not essential for viability but are required for pilus biogenesis in Escherichia coli. Journal of Bacteriology Nov;187(22):7680-6. PubMed ID: 16267292

Schilling JD, Martin SM, Hunstad DA, Patel KP, Mulvey MA, Justice SS, Lorenz RG, and Hultgren SJ. (2003) CD14- and Toll-like receptor- Dependent Activation of Bladder Epithelial Cells by Lipopolysaccharide and Type 1-piliated E. coli. Infection and Immunity Mar;71(3):1470-80. PubMed ID: 12595465

Justice SS, Hung CS, Theriot JA, Fletcher DA, Anderson GG, Footer MJ, and Hultgren SJ (2003) From the cover: Differentiation and Developmental Pathways of Uropathogenic E. coli in Urinary Tract Pathogenesis. Proceedings of the National Academy of Sciences USA 101(5): 1333-8. PubMed ID: 14739341

Justice SS, Garcia-Lara J, Rothfield LI. (2000) Cell division inhibitors SulA and MinC/MinD block septum formation at different steps in the assembly of the Escherichia coli division machinery. Moleclular Microbiology. July;37(2):410-23. PubMed ID: 10931335

Faculty and Staff
Principal Investigator: Sheryl Justice
Administrative Assistant: Mindy Law
Research Associate: Rollin Lee