Browsing by Author "Tyler, Christopher J."

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    Implementation of Mass Cytometry as a Tool for Mechanism of Action Studies in Inflammatory Bowel Disease
    (2018) Tyler, Christopher J.; Perez-Jeldres, Tamara; Ehinger, Erik; Capaldo, Brian; Karuppuchamy, Thangaraj; Boyer, Joshua D.; Patel, Derek; Dulai, Parambir; Boland, Brigid S.; Lannigan, Joanne; Eckmann, Lars; Ernst, Peter B.; Sandborn, William J.; Ho, Samuel B.; Rivera-Nieves, Jesus
    Background: Novel therapeutics for inflammatory bowel disease (IBD) are under development, yet mechanistic readouts at the tissue level are lacking. Techniques to assess intestinal immune composition could represent a valuable tool for mechanism of action (MOA) studies of novel drugs. Mass cytometry enables analysis of intestinal inflammatory cell infiltrate and corresponding molecular fingerprints with unprecedented resolution. Here, we aimed to optimize the methodology for isolation and cryopreservation of cells from intestinal tissue to allow for the potential implementation of mass cytometry in MOA studies.
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    Inherent Immune Cell Variation Within Colonic Segments Presents Challenges for Clinical Trial Design
    (2020) Tyler, Christopher J.; Guzman, Mauricio; Lundborg, Luke R.; Yeasmin, Shaila; Perez-Jeldres, Tamara; Yarur, Andres; Behm, Brian; Dulai, Parambir S.; Patel, Derek; Bamias, Giorgos; Rivera-Nieves, Jesus
    Background and Aims: Intestinal biopsy sampling during IBD trials represents a valuable adjunct strategy for understanding drug responses at the tissue level. Given the length and distinctive embryonic origins of the proximal and distal colon, we investigated whether inherent regional differences of immune cell composition could introduce confounders when sampling different disease stages, or pre/post drug administration. Here, we capitalise on novel mass cytometry technology to perform deep immunophenotyping of distinct healthy colonic segments, using the limited numbers of biopsies that can be harvested from patients.
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    Sphingosine-1-Phosphate Lyase Inhibition Alters the S1P Gradient and Ameliorates Crohn's-Like Ileitis by Suppressing Thymocyte Maturation
    (2020) Karuppuchamy, Thangaraj; Tyler, Christopher J.; Lundborg, Luke R.; Perez-Jeldres, Tamara; Kimball, Abigail K.; Clambey, Eric T.; Jedlicka, Paul; Rivera-Nieves, Jesus
    Background: Lymphocytes recirculate from tissues to blood following the sphingosine-1-phosphate (S1P) gradient (low in tissues, high in blood), maintained by synthetic and degradative enzymes, among which the S1P lyase (SPL) irreversibly degrades S1P. The role of SPL in the intestine, both during homeostasis and IBD, is poorly understood. We hypothesized that modulation of tissue S1P levels might be advantageous over S1P receptor (S1PR) agonists (eg, fingolimod, ozanimod, etrasimod), as without S1PR engagement there might be less likelihood of potential off-target effects.