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Our laboratories are focused on collaborative studies to better understand the molecular basis of epitheilal homeostasis and inflammation. Specifically, we are interested in basic mechanisms of epithelial cell migration, mucosal inflammation, leukocyte transepithelial migration, and the role of intercellular junctions in the regulation of permeability and neoplastic transformation. We are investigating the structure and function of a number of individual protein members of tight junctions and desmosomes, as well as leukocyte adhesive molecules. We are also actively investigating the signaling pathways regulating the above events. The images below are from previous and ongoing projects within our Epithelial Pathobiology Unit.
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Freeze fracture EM of Tight Junctions |
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Leukocyte infiltration of colonic epithelium in an individual with active Ulcerative Colitis. |
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JAM-A staining (green) in epitheilal crypts. Nuclei are in blue. |
ZO-1 staining (green) in non-inflamed and inflamed conditions, with neutrophils in red |
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Mutation of the JAM-A dimerization motif results in loss of JAM (green) at cell-cell contacts (Nuclei are blue).
(JBC 2004: Mandell et al.) |
Exposure of epithelial cells to IFN-gamma (right panel) induces internalization of tight junction proteins in subapical F-actin coated vacuoles
(MBC 2005: Utech et al) |
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Crystal structure of the dimerization domain of JAM-A. Blue residues represent the epitope for the dimerization inhibiting antibody J10.4 and red residues highlight the dimerization motif.
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Inhibiting ROCK acitivty (right) impairs epithelial cyst formation.
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Increased proliferation of epithelial cells in JAM-A KO mice (JEM 2007: Laukoetter et al.) |
Desmoglein 2 expression in the intestinal epithelium
(MBC 2007: Nava et al) |
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Localization of SIRP-alpha(green) and actin(red) in neutrophils before(left) and after(right) stimulation with fMLP.
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FPR-1 localization (red) in normal human colonic mucosa. (Nuclei are in blue.)
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The surface of SIRPalpha.D1 mediates binding to CD47. Critical residues (red) and non-critical residues (green) are mapped onto the recently reported SIRPalpha.D1 crystal structure. (JI 2007: Lee et al.)
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Rho GTPAse co-localizes with internalized occludin(MBC 2007: Samarin et al.)
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