This application will study two hypotheses: 1) the ability of intestinal epithelial cells to respond to an inflammatory stimulus is dependent on the state of cell differentiation and 2) nutrients including butyrate and vitamin D are capable of inducing differentiation and as such can inhibit expression by epithelial cells of the intestine of inflammatory mediators. There are three Specific Aims: 1) to determine the mechanism of differentiation by butyrate and vitamin D concomitant with inhibition of IL-8 expression. The role of histone hyperacetylation will be explored for butyrate mediated differentiation and the role of intracellular calcium and vitamin D receptor studied for vitamin D induced differentiation. The next Specific Aim examines IL-8 gene expression with regard to transcriptional repression and MRNA stability, definition of promotor sequences of the IL-8 gene which inhibit transcription as well as mapping of Dnase 1 hypersensitive sites. Finally, to ascertain cis-acting elements by Dnase 1 footprinting, electrophoretic mobility shift assay and site directed mutagenesis in chimeric and minigene constructs of the IL-8 gene.
| Bryson, Alexandra L; Hwang, Young; Sherrill-Mix, Scott et al. (2015) Covalent Modification of Bacteriophage T4 DNA Inhibits CRISPR-Cas9. MBio 6:e00648 |
| Dollive, Serena; Chen, Ying-Yu; Grunberg, Stephanie et al. (2013) Fungi of the murine gut: episodic variation and proliferation during antibiotic treatment. PLoS One 8:e71806 |
| Han, Daehee; Walsh, Matthew C; Cejas, Pedro J et al. (2013) Dendritic cell expression of the signaling molecule TRAF6 is critical for gut microbiota-dependent immune tolerance. Immunity 38:1211-22 |
| Dollive, Serena; Peterfreund, Gregory L; Sherrill-Mix, Scott et al. (2012) A tool kit for quantifying eukaryotic rRNA gene sequences from human microbiome samples. Genome Biol 13:R60 |
| Albenberg, Lindsey G; Lewis, James D; Wu, Gary D (2012) Food and the gut microbiota in inflammatory bowel diseases: a critical connection. Curr Opin Gastroenterol 28:314-20 |
| Minot, Samuel; Grunberg, Stephanie; Wu, Gary D et al. (2012) Hypervariable loci in the human gut virome. Proc Natl Acad Sci U S A 109:3962-6 |
| Wu, Gary D; Chen, Jun; Hoffmann, Christian et al. (2011) Linking long-term dietary patterns with gut microbial enterotypes. Science 334:105-8 |
| Minot, Samuel; Sinha, Rohini; Chen, Jun et al. (2011) The human gut virome: inter-individual variation and dynamic response to diet. Genome Res 21:1616-25 |
| Wu, Gary D; Lewis, James D; Hoffmann, Christian et al. (2010) Sampling and pyrosequencing methods for characterizing bacterial communities in the human gut using 16S sequence tags. BMC Microbiol 10:206 |
| Hildebrandt, Marie A; Hoffmann, Christian; Sherrill-Mix, Scott A et al. (2009) High-fat diet determines the composition of the murine gut microbiome independently of obesity. Gastroenterology 137:1716-24.e1-2 |
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