Theses and Dissertations from UMD

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New submissions to the thesis/dissertation collections are added automatically as they are received from the Graduate School. Currently, the Graduate School deposits all theses and dissertations from a given semester after the official graduation date. This means that there may be up to a 4 month delay in the appearance of a give thesis/dissertation in DRUM

More information is available at Theses and Dissertations at University of Maryland Libraries.

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2010 - 20122

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    Estrogen and Progesterone enhance Neisseria gonorrhoeae Transmigration across a Polarized Monolayer via a Mechanism that Hijacks EGFR
    (2012) Edwards, Vonetta Lisa; Song, Wenxia; Cell Biology & Molecular Genetics; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)
    Gonorrhea, a common sexually transmitted infection, is caused by the gram-negative bacterium Neisseria gonorrhoeae. In the female reproductive tract, gonococci (GC) initiate infection at the apical surface of columnar endocervical epithelial cells. These cells provide a physical barrier against mucosal pathogens by forming continuous apical junctional complexes between neighboring cells. This study examines the interaction of GC with polarized epithelial cells. We show that viable, but not gentamicin killed, GC preferentially localize at the apical side of the cell-cell junction in polarized endometrial and colonic epithelial cells, HEC-1-B and T84, respectively. In GC infected epithelial cells, continuous apical junctional complexes are disrupted, and the junction-associated protein β-catenin is redistributed from the apical junction to the cytoplasm and to GC adherent sites. However, GC inoculation does not change the overall cellular level of junctional proteins. This redistribution of junctional proteins is associated with a decrease in the apical junction's barrier function against the lateral movement between the apical and basolateral membranes, but not against the permeability through the paracellular space. Disruption of the apical junction by removing calcium increases GC transmigration across the epithelial monolayer. GC inoculation induces the phosphorylation of both epidermal growth factor receptor (EGFR) and β-catenin, while inhibition of EGFR kinase significantly reduces both GC-induced β-catenin redistribution and GC transmigration. These results suggest a relationship between junction protein redistribution from the plasma membrane with the resultant weakening of the junctional complex, and an increase in the ability of GC to transmigrate. The presence of the female sex hormones estrogen and progesterone, lead to an increased degree of disruption of the junctional complex and enhance GC transmigration across the monolayer. Therefore, GC are capable of weakening the apical junction and the polarity of epithelial cells via activating EGFR, which facilitates GC transmigration across the epithelium.
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    The Role of ErbB Receptors in Neisseria gonorrhoeae Invasion of Genital Epithelial Cells
    (2010) Swanson, Karen; Song, Wenxia; Cell Biology & Molecular Genetics; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)
    Neisseria gonorrhoeae, the causative agent of the sexually transmitted infection gonorrhea, adheres to and invades genital epithelial cells. This study investigates host components that are used by the bacteria for their entry into epithelial cells. I found that the interaction of gonococci with the surface of HEC-1-B, a human endometrial carcinoma, and ME180, a human cervical epidermoid carcinoma, caused redistribution of both epidermal growth factor receptor (EGFR) and ErbB2, a related family member. Both EGFR and ErbB2 were translocated from the basolateral to the apical membrane in polarized HEC-1-B cells and concentrated under the microcolonies. Gonococcal infection increased EGFR and ErbB2 phosphorylation, indicating activation of the receptors. Kinase inhibitors of EGFR and ErbB2 inhibited and enhanced bacterial invasion, respectively, but had no effect on gonococcal adherence or the recruitment of EGFR and ErbB2 to the microcolonies. Gonococcal inoculation upregulated the transcription levels and matrix metalloproteinases (MMP)-mediated surface shedding of ligands of EGFR. Inhibition of the surface shedding of EGFR ligands by an MMP inhibitor and by heparin wash reduced gonococcal invasion without altering their adherence. N. gonorrhoeae induced the activation of the MAP Kinase ERK, PI3K/AKT and PLCγ signaling pathways in an EGFR tyrosine kinase-dependent manner. Blocking Ca2+ flux, the downstream pathway of PLCγ but not ERK and PI3K by inhibitors reduced gonococcal invasion. These data indicate that N. gonorrhoeae utilizes host signaling pathways to drive its invasion. The bacteria modulates host signaling by recruiting and activating EGFR and ErbB2. N. gonorrhoeae induces EGFR activation by increasing the expression and MMP-mediated shedding of EGFR ligands.