Digestive Health Center

  • Development and Digestive Diseases

    Marshall (Chip) Montrose, PhD
    Professor and Chairman
    Department of Molecular and Cellular Physiology

    Description of Research

    Dr. Montrose studies the regulation of epithelial defenses and ion transport in stomach and intestine. His work uniquely explores the dynamic events that occur in microscopic regions of living native tissue. He is testing the hypothesis that regulation of the extracellular pH directly above the gastric epithelium is mediated by the SLC26A9 bicarbonate transporter, and that regulation of this transporter by cycloxygenase-1 is integral to the ability of the tissue to recover from microscopic damage to the epithelium. He uses two-photon light absorption to produce micro-lesions (1-4 cells) targeted at the gastric surface epithelium, and monitors the tissue recovery in real time using two-photon and confocal microscopy. He also studies the mechanisms that allow the epithelial barrier in the small intestine to be sustained during either acute cell damage or during physiologic cell renewal. Using transgenic mice expressing a fluorescent tight junction protein (ZO-1), he is examining the subcellular redistribution of tight junction proteins that is necessary for barrier function to be sustained as a cell is being expelled from the monolayer. Additionally, Dr. Montrose is studying the regulation and function of NHE2 and NHE3 in the large intestine. The relative contributions of these two Na+/H+ exchanger isoforms to sodium and water absorption remains uncertain. He is testing several hypotheses about the differential responsiveness of these two isoforms to extracellular and intracellular pH microdomains near the membranes (using cells transfected with fusion proteins combining NHE and fluorescent proteins to visualize protein trafficking), and using pharmacologic and genetic approaches with live tissue confocal microscopy to ask if Na+/H+ exchange function is present in the base of colonic crypts (long believed to be an exclusively secretory structure) of NHE knockout mice.

    Collaborations

    Dr. Montrose collaborates with Dr. Shull to explore the function of NHE proteins in the colonic crypt epithelium using knockout and transgenic animals. Dr. Shroyer collaborates with Dr. Montrose to study animals that lack goblet cells in the small intestine. Anticipated Core use: Integrative Morphology Core.

 
  • Research image.

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    Research image.

    Gastric surface intracellular pH response to photodamage. Confocal reflectance (A) and SNARF-5F fluorescence images of 620–680 nm (B) and 550–600 nm (C) emission illustrate dye retention in damaged cell areas (white region). Bar = 25 μm. D: pHi was measured in control, EIPA, and H2DIDS-treated mice 10 min after photodamage. Values are reported for damaged (D) cells, compared with healthy near (N) and far (F) cells. Values represent mean ± SE. *P < 0.05 vs. control. Figure from Am J Physiol Gastrointest Liver Physiol, 2010;299:G255-264.