{"id":{"repo_id":"uiuc","oai_identifier":"oai:www.ideals.illinois.edu:2142/115585"},"canonical_url":"https://search.dev.ndltd.org/etd/uiuc/oai:www.ideals.illinois.edu:2142/115585","repository":{"repo_id":"uiuc","name":"University of Illinois - Urbana-Champaign","base_url":"https://www.ideals.illinois.edu/oai-pmh"},"display":{"title":"Genotoxic remodeling of the host epithelium","abstract":"Submission published under a 24 month embargo labeled 'U of I Access', the embargo will last until 2024-05-01","abstract_html":"Submission published under a 24 month embargo labeled 'U of I Access', the embargo will last until 2024-05-01","abstract_has_math":false,"creators":["Lieu, Dfeau Jia"],"institution":"University of Illinois at Urbana-Champaign","degree_name":"Ph.D.","degree_level":"Dissertation","degree_discipline":"Microbiology","degree_department":null,"school":null,"contributors":["Blanke, Steven R","Whitaker, Rachel J","Wilson, Brenda A","Olsen, Gary J"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2022,"date_issued":"2022-05","date_published":"2022-05","updated_at":"2026-07-22T22:24:54Z","subjects":["cytolethal distending toxins","CDT","autophagy","SNAI1","DNA damage response","genotoxicity"],"languages":["en","eng"],"rights":["Copyright 2022 Dfeau Lieu"],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"https://hdl.handle.net/2142/115585","outbound_label":"Handle","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Blanke, Steven R","Whitaker, Rachel J","Wilson, Brenda A","Olsen, Gary J"]},{"key":"dc:creator","label":"Author","values":["Lieu, Dfeau Jia"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2022-05","2022-04-21"]},{"key":"dc:type","label":"Dc Type","values":["text","Thesis"]},{"key":"thesis:degree_discipline","label":"Discipline","values":["Microbiology"]},{"key":"thesis:degree_level","label":"Degree Level","values":["Dissertation"]},{"key":"thesis:degree_name","label":"Degree Name","values":["Ph.D."]},{"key":"thesis:institution_name","label":"Thesis Institution Name","values":["University of Illinois at Urbana-Champaign"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["cytolethal distending toxins","CDT","autophagy","SNAI1","DNA damage response","genotoxicity"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language","label":"Dc Language","values":["en","eng"]},{"key":"dc:rights","label":"Dc Rights","values":["Copyright 2022 Dfeau Lieu"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["https://hdl.handle.net/2142/115585"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["Submission published under a 24 month embargo labeled 'U of I Access', the embargo will last until 2024-05-01","The student, Dfeau Lieu, accepted the attached license on 2022-04-19 at 15:28.","The student, Dfeau Lieu, submitted this Dissertation for approval on 2022-04-19 at 15:39.","This Dissertation was approved for publication on 2022-04-21 at 15:51.","DSpace SAF Submission Ingestion Package generated from Vireo submission #17815 on 2022-11-11 at 12:06:13","Epithelial barriers, especially that found in the intestine, are highly dynamic, needing to regulate the transport of nutrients and cellular material, while at the same time resisting damage from environmental stresses and preventing pathogen infiltration. Central to maintaining the ability of epithelial cells to appropriately respond to stress and pathogenic bacteria is a cellular degradative process known as autophagy which is responsible for the recycling of intracellular components such as aggregated proteins, damaged organelles, and intracellular pathogens. Here, we report that exposure of epithelial cells to genotoxins, known as cytolethal distending toxins (CDTs), secreted by human mucosal bacterial pathogens impairs formation of specialized vacuoles, autophagosomes, which are required for the sequestration of intracellular components during autophagy. Our studies revealed that CDT treatment of epithelial cells reduced the number of autophagosomes formed in response to potent inducers of autophagy. CDT-mediated impairment of autophagosome formation was dependent on CDT- mediated DNA damage and subsequent DNA damage response. CDT treated cells had diminished levels of cellular LC3-I, a structural protein whose lipidation to LC3-II is necessary for autophagosome formation. Our studies support a yet unrecognized strategy by which some pathogens can interfere with autophagosome formation. In addition to impacting the autophagic process, our studies also identified how genomic instability induced by CDT leads to the reduction of SNAI1, a transcription factor that facilitates intestinal lineage allocation and is critical for epithelial-mesenchymal transitions that occur during human development and metastatic cancers. These studies demonstrate that CDT intoxication leads to cellular changes far beyond simply the often- cited cell cycle arrest and suggests a role for CDTs in disrupting epithelial function through the perturbation of cellular homeostasis."]},{"key":"dc:format","label":"Dc Format","values":["application/pdf"]},{"key":"dc:title","label":"Title","values":["Genotoxic remodeling of the host epithelium"]}]}],"canonical_facts":{"dc:contributor":["Blanke, Steven R","Whitaker, Rachel J","Wilson, Brenda A","Olsen, Gary J"],"dc:creator":["Lieu, Dfeau Jia"],"dc:date":["2022-05","2022-04-21"],"dc:description":["Submission published under a 24 month embargo labeled 'U of I Access', the embargo will last until 2024-05-01","The student, Dfeau Lieu, accepted the attached license on 2022-04-19 at 15:28.","The student, Dfeau Lieu, submitted this Dissertation for approval on 2022-04-19 at 15:39.","This Dissertation was approved for publication on 2022-04-21 at 15:51.","DSpace SAF Submission Ingestion Package generated from Vireo submission #17815 on 2022-11-11 at 12:06:13","Epithelial barriers, especially that found in the intestine, are highly dynamic, needing to regulate the transport of nutrients and cellular material, while at the same time resisting damage from environmental stresses and preventing pathogen infiltration. Central to maintaining the ability of epithelial cells to appropriately respond to stress and pathogenic bacteria is a cellular degradative process known as autophagy which is responsible for the recycling of intracellular components such as aggregated proteins, damaged organelles, and intracellular pathogens. Here, we report that exposure of epithelial cells to genotoxins, known as cytolethal distending toxins (CDTs), secreted by human mucosal bacterial pathogens impairs formation of specialized vacuoles, autophagosomes, which are required for the sequestration of intracellular components during autophagy. Our studies revealed that CDT treatment of epithelial cells reduced the number of autophagosomes formed in response to potent inducers of autophagy. CDT-mediated impairment of autophagosome formation was dependent on CDT- mediated DNA damage and subsequent DNA damage response. CDT treated cells had diminished levels of cellular LC3-I, a structural protein whose lipidation to LC3-II is necessary for autophagosome formation. Our studies support a yet unrecognized strategy by which some pathogens can interfere with autophagosome formation. In addition to impacting the autophagic process, our studies also identified how genomic instability induced by CDT leads to the reduction of SNAI1, a transcription factor that facilitates intestinal lineage allocation and is critical for epithelial-mesenchymal transitions that occur during human development and metastatic cancers. These studies demonstrate that CDT intoxication leads to cellular changes far beyond simply the often- cited cell cycle arrest and suggests a role for CDTs in disrupting epithelial function through the perturbation of cellular homeostasis."],"dc:format":["application/pdf"],"dc:identifier":["https://hdl.handle.net/2142/115585"],"dc:language":["en","eng"],"dc:rights":["Copyright 2022 Dfeau Lieu"],"dc:subject":["cytolethal distending toxins","CDT","autophagy","SNAI1","DNA damage response","genotoxicity"],"dc:title":["Genotoxic remodeling of the host epithelium"],"dc:type":["text","Thesis"],"thesis:degree_discipline":["Microbiology"],"thesis:degree_level":["Dissertation"],"thesis:degree_name":["Ph.D."],"thesis:institution_name":["University of Illinois at Urbana-Champaign"]},"updated_at":"2026-07-22T22:24:54Z"}