Kelli L. Hvorecny

Research Summary

Regulation of ABC-Transporter Trafficking by Epoxide Hydrolases. Epoxide hydrolases (EHs) convert an epoxide group to a vicinal diol. Each hydrolase possesses a specific substrate profile, which has the potential to be implemented in epoxide deconstruction or vicinal diol biosynthesis. Previous work by our group characterized Cif (CFTR Inhibitory Factor), an EH secreted by the bacteria Pseudomonas aeruginosa. Our collaborators in the Stanton and O'Toole labs showed that Cif causes the down regulation of the ABC-transporter CFTR in an epithelial-bacterial co-cuture model. Recent work (C. D. Bahl, unpublished) shows enzymatically dead mutants have no effect on CFTR levels, suggesting Cif acts on endogenous epoxy-lipids and may interrupt or co-opt an epithelial cell pathway, such as the USP10 de-ubiquitination pathway that modulates CFTR trafficking and degradation. The pathway therefore appears to utilize endogenous epoxides to regulate ABC transporter trafficking, a novel mechanism linking lipid signaling and protein trafficking. Currently, we are setting up over-expression and knock-down systems in lung epithelial cells to identify endogenous enzymes involved in this pathway, as well as initiating in vitro biochemical and structural characterization of the EHs.

Publications

Bahl CD, Hvorecny KL, Bridges AA, Ballok AE, Bomberger JM, Cady KC, O'Toole GA, Madden DR. (2014) Signature motifs identify an Acinetobacter Cif virulence factor with epoxide hydrolase activity. J Biol Chem. 289(11): 7460-9.

Newell P.D., Yoshioka S., Hvorecny K.L., Monds R.D., O'Toole G.A. (2011) Systematic analysis of dyguanylate cyclases that promote biofilm formation by Pseudomonas fluorescens Pf0-1. J Bacteriol. 193: 4685-98.

Hvorecny K.L., Prelich G.C. (2010) A systematic CEN library of the Saccharomyces cerevisiae genome. Yeast. 27: 861-5.