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Moran, Christopher

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Moran

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Christopher

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Moran, Christopher
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    Genetic variants in cellular transport do not affect mesalamine response in ulcerative colitis
    (Public Library of Science, 2018) Moran, Christopher; Huang, Hailiang; Rivas, Manuel; Kaplan, Jess; Daly, Mark; Winter, Harland
    Background and aims Mesalamine is commonly used to treat ulcerative colitis (UC). Although mesalamine acts topically, in vitro data suggest that intracellular transport is required for its beneficial effect. Genetic variants in mucosal transport proteins may affect this uptake, but the clinical relevance of these variants has not been studied. The aim of this study was to determine whether variants in genes involved in cellular transport affect the response to mesalamine in UC. Methods: Subjects with UC from a 6-week clinical trial using multiple doses of mesalamine were genotyped using a genome-wide array that included common exome variants. Analysis focused on cellular transport gene variants with a minor allele frequency >5%. Mesalamine response was defined as improvement in Week 6 Physician’s Global Assessment (PGA) and non-response as a lack of improvement in Week 6 PGA. Quality control thresholds included an individual genotyping rate of >90%, SNP genotyping rate of >98%, and exclusion for subjects with cryptic relatedness. All included variants met Hardy-Weinberg equilibrium (p>0.001). Results: 457 adults with UC were included with 280 responders and 177 non-responders. There were no common variants in transporter genes that were associated with response to mesalamine. The genetic risk score of responders was similar to that of non-responders (p = 0.18). Genome-wide variants demonstrating a trend towards mesalamine response included ST8SIA5 (p = 1x10-5). Conclusions: Common transporter gene variants did not affect response to mesalamine in adult UC. The response to mesalamine may be due to rare genetic events or environmental factors such as the intestinal microbiome.
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    Focally Enhanced Gastritis in Newly Diagnosed Pediatric Inflammatory Bowel Disease
    (Ovid Technologies (Wolters Kluwer Health), 2013) Ushiku, Tetsuo; Moran, Christopher; Lauwers, Gregory Y.
    Although the significance of focally enhanced gastritis (FEG) as a marker of Crohn disease (CD) in adults has been contested, several studies suggest that it may be more specific of CD in pediatric patients. This study describes the detailed histologic features of FEG in pediatric inflammatory bowel disease (IBD) and clarifies its association with CD. A series of 119 consecutive newly diagnosed IBD patients (62 CD cases, 57 ulcerative colitis [UC] cases) with upper and lower gastrointestinal biopsies were evaluated. The histology of the gastric biopsies was reviewed blinded to final diagnoses and compared with age-matched healthy controls (n=66). FEG was present in 43% of IBD patients (CD 55% vs. UC 30%, P=0.0092) and in 5% of controls. Among CD patients, FEG was more common in younger patients (73% in children aged 10 y and below, 43% in children above 10 y of age, P=0.0358), with the peak in the 5- to 10-year age group (80%). The total number of glands involved in each FEG focus was higher in UC (6.4±5.1 glands) than in CD (4.0±3.0 glands, P=0.0409). Amongst the CD cohort, patients with FEG were more likely than those without FEG to have active ileitis (79% vs. 40%, P=0.0128) and granulomas elsewhere in the gastrointestinal tract (82% vs. 43%, P=0.0016). There was no correlation between FEG and other gastrointestinal findings of UC. We demonstrate that differences in FEG seen in pediatric CD and UC relate to not only their frequencies but also the morphology and relationship with other gastrointestinal lesions. Further, FEG is associated with disease activity and the presence of granulomas in pediatric CD.
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    Resection of Acquired Mucosal Web in Crohn Disease
    (Ovid Technologies (Wolters Kluwer Health), 2013) Moran, Christopher; Kelsey, Peter; Lauwers, Gregory Y.; Biller, Jeffrey
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    Sequencing Three Crocodilian Genomes to Illuminate the Evolution of Archosaurs and Amniotes
    (BioMed Central, 2012) St John, John A; Braun, Edward L; Isberg, Sally R; Miles, Lee G; Chong, Amanda Y; Gongora, Jaime; Dalzell, Pauline; Bed'Hom, Bertrand; Burgess, Shane C; Cooksey, Amanda M; Castoe, Todd A; Densmore, Llewellyn D; Drew, Jennifer C; Faircloth, Brant C; Greenwold, Matthew J; Hoffmann, Federico G; Howard, Jonathan M; Iguchi, Taisen; Janes, Daniel E; Khan, Shahid Yar; Kohno, Satomi; de Koning, AP Jason; Lance, Stacey L; McCarthy, Fiona M; McCormack, John E; Merchant, Mark E; Peterson, Daniel G; Pollock, David D; Pourmand, Nader; Raney, Brian J; Roessler, Kyria A; Sanford, Jeremy R; Sawyer, Roger H; Schmidt, Carl J; Triplett, Eric W; Tuberville, Tracey D; Venegas-Anaya, Miryam; Howard, Jason T; Jarvis, Erich D; Guillette, Louis J; Glenn, Travis C; Ray, David A; Moran, Christopher; Abzhanov, Arkhat; Crawford, Nicholas G.; Moran, Christopher; Edwards, Scott; Fujita, Matthew; Green, Richard E.
    The International Crocodilian Genomes Working Group (ICGWG) will sequence and assemble the American alligator (Alligator mississippiensis), saltwater crocodile (Crocodylus porosus) and Indian gharial (Gavialis gangeticus) genomes. The status of these projects and our planned analyses are described.