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RNA interference (RNAi) has great potential as a tool for studying gene function in mammals. However, the specificity and magnitude of the in vivo response to RNAi remains to be fully characterized. A molecular and phenotypic comparison of a genetic knockout mouse and the corresponding knockdown version would help clarify the utility of the RNAi approach.(More)
In rodents, treatment with peroxisome proliferator-activated receptor alpha (PPARalpha) agonists results in peroxisome proliferation, hepatocellular hypertrophy, and hepatomegaly. Drugs in the fibrate class of PPARalpha agonists have also been reported to produce rare skeletal muscle toxicity. Although target-driven hepatic effects of PPARalpha treatment(More)
Chromatin immunoprecipitation (ChIP) studies were conducted in human hepatocytes treated with rifampicin in order to identify new pregnane-X receptor (PXR) target genes. Genes, both previously known to be involved and not known to be involved in drug disposition, with PXR response elements (PXREs) located upstream, within or downstream from their(More)
Toxicity is a major cause of failure in drug development. A toxicogenomic approach may provide a powerful tool for better assessing the potential toxicity of drug candidates. Several approaches have been reported for predicting hepatotoxicity based on reference compounds with well-studied toxicity mechanisms. We developed a new approach for assessing(More)
Uncovering pathways underlying drug-induced toxicity is a fundamental objective in the field of toxicogenomics. Developing mechanism-based toxicity biomarkers requires the identification of such novel pathways and the order of their sufficiency in causing a phenotypic response. Genome-wide RNA interference (RNAi) phenotypic screening has emerged as an(More)
Site-specific protein labeling are powerful means of protein research and engineering; however, new and improved labeling methods are greatly needed. Split inteins catalyze a protein trans-splicing reaction that can be used for enzymatic and nearly seamless protein labeling. Non-canonical S11 split intein has been used in an earlier method of protein(More)
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