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Omics analyses of global dysregulation in Primary Biliary Cholangitis

  • Author / Creator
    Dutra, Bruna
  • Primary Biliary Cholangitis (PBC) is a complex cholestatic liver disorder with both environmental and genetic factors that contribute to disease. While the etiology remains poorly understood, our lab continues to characterize the role of a human betaretrovirus (HBRV) in the disease process. Based on prior proteomic studies in biliary epithelial cells from patients with PBC, we have identified dysregulation in the splicing machinery. This process is necessary for the maturation of mRNA molecules by the removal of introns and reconnection of exons. Based on the knowledge that viruses systemically perturb cellular processes, we hypothesized that splicing might be globally disrupted and possibly related to patient outcomes. Using the relevant control samples, we performed additional transcriptomics and proteomics analyses using biliary epithelial cells (BEC) from patients with PBC and transcriptomics analysis on the peripheral blood of PBC patients. We found that splicing and other essential cellular pathways are deregulated in the blood and BEC of PBC patients, and the process is more advanced in PBC patients with worse prognoses. In addition, many of the proteins and genes dysregulated in the PBC patients have been previously linked with viral infection, supporting our hypothesis linking altered splicing with viral pathogenesis. These findings may be clinically significant, as they bring to the light new evidence of pathogenic mechanisms implicated in the disease process. Based on these and other studies relating to the metabolic and other essential cellular processes that may be dysregulation by viral infection, we believe our data warrants further study investigating and validating the role of HBRV in generating these cellular changes in vitro

  • Subjects / Keywords
  • Graduation date
    Fall 2021
  • Type of Item
    Thesis
  • Degree
    Master of Science
  • DOI
    https://doi.org/10.7939/r3-21yn-c941
  • License
    This thesis is made available by the University of Alberta Libraries with permission of the copyright owner solely for non-commercial purposes. This thesis, or any portion thereof, may not otherwise be copied or reproduced without the written consent of the copyright owner, except to the extent permitted by Canadian copyright law.