A5080210254- Barrier Structure and Function Studies
- Gut microbiota and health
- Inflammatory Bowel Disease
- Helicobacter pylori-related gastroenterology studies
- Connexins and lens biology
- Immune Response and Inflammation
- Ion Transport and Channel Regulation
- Microscopic Colitis
- Gastrointestinal motility and disorders
- Neurological Disease Mechanisms and Treatments
- Immune Cell Function and Interaction
- Cell Adhesion Molecules Research
- Drug Transport and Resistance Mechanisms
- Pancreatic function and diabetes
- Digestive system and related health
- Clostridium difficile and Clostridium perfringens research
- Caveolin-1 and cellular processes
- Viral gastroenteritis research and epidemiology
- T-cell and B-cell Immunology
- Gastric Cancer Management and Outcomes
- IL-33, ST2, and ILC Pathways
- Cancer-related molecular mechanisms research
- Mycobacterium research and diagnosis
- Esophageal Cancer Research and Treatment
- Escherichia coli research studies
Brigham and Women's Hospital
2015-2024
Harvard University
2015-2024
University of Chicago
2014-2023
Boston Children's Hospital
2018-2022
Woman's Hospital
2020-2021
Center for Systems Biology
2020
Molecular Devices
2020
Mentor
2017
Motility (United States)
2017
University of Illinois Chicago
2015
Tight junctions serve as the rate-limiting barrier to passive movement of hydrophilic solutes across intestinal epithelia. After activation Na+-glucose cotransport, permeability tight is increased. Because previous analyses this physiological junction regulation have been restricted intact mucosae, dissection mechanisms underlying process has limited. To characterize process, we developed a reductionist model consisting Caco-2 epithelial cells transfected with cotransporter, SGLT1....
Epithelial tight junctions form a barrier against passive paracellular flux. This is regulated by complex physiologic and pathophysiologic signals that acutely fine-tune junction permeability. Although actomyosin contraction myosin light chain phosphorylation are clearly involved in some forms of regulation, the contributions other signaling events role this response poorly understood. Here we ask if activation kinase alone sufficient to induce downstream regulation. We use confluent...
Epithelial paracellular barrier function, determined primarily by tight junction permeability, is frequently disrupted in disease. In the intestine, loss can be mediated tumor necrosis factor (alpha) (TNF) signaling and epithelial myosin light chain kinase (MLCK) activation. However, TNF induces only limited alteration of morphology, events that couple structural reorganization to regulation have not been defined. We used vivo imaging transgenic mice expressing fluorescent-tagged occludin...
Mucosal organs such as the intestine are supported by a rich and complex underlying vasculature. For this reason, intestine, particularly barrier-protective epithelial cells, susceptible to damage related diminished blood flow concomitant tissue hypoxia. We sought identify compensatory mechanisms that protect barrier during episodes of intestinal Initial studies examining T84 colonic cells revealed function is uniquely resistant changes elicited A search for intestinal-specific, factors...
The rho family of GTP-binding proteins regulates actin filament organization. In unpolarized mammalian cells, regulate the assembly actin-containing stress fibers at cell-matrix interface. Polarized epithelial in contrast, are tall and cylindrical with well developed intercellular tight junctions that permit them to behave as biologic barriers. We report filamentous organization preferentially apical pole polarized intestinal cells and, so doing, influences permeability associated junctions....
Based on preliminary evidence indicating that a cell-associated protein of U937 (a human monocyte-like cell line) possessed cofactor activity and was not the C3b/C4b receptor, we sought to further characterize this protein. A sequential four-column purification procedure devised includes C3(H2O) affinity chromatography isolate in reasonable yields purity several other lines. its pattern Mr SDS-PAGE, acidic pI, ligand specificity, it is identical recently described or C3b-binding membrane...
The tight junction defines epithelial organization. Structurally, the is comprised of transmembrane and membrane-associated proteins that are thought to assemble into stable complexes determine function. In this study, we measure protein dynamics in live confluent Madin–Darby canine kidney monolayers using fluorescence recovery after photobleaching related methods. Mathematical modeling shows majority claudin-1 (76 ± 5%) stably localized at junction. contrast, occludin (71 3%) diffuses...
A tight junction (TJ) protein, claudin-1 (CLDN1), was identified recently as a key factor for hepatitis C virus (HCV) entry. Here, we show that another TJ occludin, is also required HCV Mutational study of CLDN1 revealed its junctional distribution plays an important role in mediating viral Together, these data support the model which enters liver cells from TJ. Interestingly, infection Huh-7 hepatoma downregulated expression and preventing superinfection. The altered protein may contribute...
Mucin-type O-linked oligosaccharides (O-glycans) are primary components of the intestinal mucins that form mucus gel layer overlying gut epithelium. Impaired expression O-glycans has been observed in patients with ulcerative colitis (UC), but its role etiology this disease is unknown. Here, we report mice epithelial cell–specific deficiency core 1–derived O-glycans, predominant developed spontaneous resembled human UC, including massive myeloid infiltrates and crypt abscesses. The manifested...