• Login
    View Item 
    •   Home
    • Theses and Dissertations
    • Dissertations
    • View Item
    •   Home
    • Theses and Dissertations
    • Dissertations
    • View Item
    JavaScript is disabled for your browser. Some features of this site may not work without it.

    Browse

    All of KAUSTCommunitiesIssue DateSubmit DateThis CollectionIssue DateSubmit Date

    My Account

    Login

    Quick Links

    Open Access PolicyORCID LibguidePlumX LibguideSubmit an Item

    Statistics

    Display statistics

    Regulation of the O-glycan-type Sialyl-Lewis X (sLex) Bio-synthesis Pathway during Cell Transformation Programs: Epithelial-Mesenchymal Transition (EMT) and Molecular Subtypes in Breast Carcinoma and Human T Cell Activation

    • CSV
    • RefMan
    • EndNote
    • BibTex
    • RefWorks
    Thumbnail
    Name:
    Ayman Abuelela Dissertation.pdf
    Size:
    144.6Mb
    Format:
    PDF
    Description:
    Ayman Abuelela Dissertation
    Download
    Type
    Dissertation
    Authors
    AbuElela, Ayman cc
    Advisors
    Merzaban, Jasmeen cc
    Committee members
    Magistretti, Pierre J. cc
    Gao, Xin cc
    Kubes, Paul
    Cummings, Richard
    Program
    Bioscience
    KAUST Department
    Biological and Environmental Sciences and Engineering (BESE) Division
    Date
    2017-12
    Permanent link to this record
    http://hdl.handle.net/10754/626306
    
    Metadata
    Show full item record
    Abstract
    During tumor progression and development of distant metastases, a subset of cancer cells undergoes transformation programs, such as epithelial-mesenchymal transition (EMT), to acquire enhanced migratory attributes to commence the metastatic cascade with the intension of achieving an active cell adhesion molecule-mediated organ-specific homing. Similarly, naive T cells reform the assemblage of their surface adhesion molecules during differentiation to activated T cells in order to successfully home to sites of inflammation and other extra-lymphoid organs for surveillance purposes. Sialyl-Lewis X (sLex) is well-known for mediating the homing of epithelial circulating tumor cellss (CTCs) and activated T cells to target sites through the interaction with endothelial selectins. Since glycan structures are not directly encoded by the genome, their expression is dependent on the glycosyltransferase (GT) expression and activity. Yet, the modulation of GTs during breast cancer transformation and in different molecular subtypes is still unknown. In addition, although the regulation of GTs during T cell activation is well-understood, the regulation at the epigenetic level is lacking. O-glycan-type sLex expression and E-selectin binding under static and flow conditions varies among molecular subtypes of breast cancer and upon the induction of EMT which is linked to the expression patterns of GTs. GTs displayed a significant prognostic value of in the association with the patients' survival profiles and in the ability to predict the breast cancer molecular subtypes from the expression data of a random patient sample. Also, GTs were able to differentiate between tumor and their normal counterparts as well as cancer types and glioblastoma subtypes. On the other hand, we studied the regulation of GTs in human CD4+ memory T cells compared to the naive cells at the epigenetic level. Memory T cell subsets demonstrated differential chromatin accessibility and histone marks within the promoters of the GTs genes. Moreover, they showed differential binding of pioneer and nonpioneer transcription factors (TFs). We proposed a model for the regulation of FUT7 during T cell activation that relies on the interplay between chromatin-remodeling and cell-fate-specifying TFs. Furthermore, we developed a fluorescent multiplex cell rolling (FMCR) assay to study the cell adhesion properties under physiological conditions. Compared to the conventional parallel plate flow chamber (PPFC) assay, the novel technique posses a high-throughput capacity which helps eliminate the inter-experimental variation problem by running multiple samples simultaneously and under competitive settings. We also developed a real-time analysis pipeline that enhanced the statistical power of the assay. Overall these modifications to the traditional parallel plate assay improves the reliability and results along with saving time and effort.
    Citation
    AbuElela, A. (2017). Regulation of the O-glycan-type Sialyl-Lewis X (sLex) Bio-synthesis Pathway during Cell Transformation Programs: Epithelial-Mesenchymal Transition (EMT) and Molecular Subtypes in Breast Carcinoma and Human T Cell Activation. KAUST Research Repository. https://doi.org/10.25781/KAUST-Q9851
    DOI
    10.25781/KAUST-Q9851
    ae974a485f413a2113503eed53cd6c53
    10.25781/KAUST-Q9851
    Scopus Count
    Collections
    Biological and Environmental Sciences and Engineering (BESE) Division; Bioscience Program; Dissertations; Dissertations

    entitlement

     
    DSpace software copyright © 2002-2021  DuraSpace
    Quick Guide | Contact Us | Send Feedback
    Open Repository is a service hosted by 
    Atmire NV
     

    Export search results

    The export option will allow you to export the current search results of the entered query to a file. Different formats are available for download. To export the items, click on the button corresponding with the preferred download format.

    By default, clicking on the export buttons will result in a download of the allowed maximum amount of items. For anonymous users the allowed maximum amount is 50 search results.

    To select a subset of the search results, click "Selective Export" button and make a selection of the items you want to export. The amount of items that can be exported at once is similarly restricted as the full export.

    After making a selection, click one of the export format buttons. The amount of items that will be exported is indicated in the bubble next to export format.