{"id":{"repo_id":"uwo","oai_identifier":"oai:uwo.scholaris.ca:20.500.14721/32490"},"canonical_url":"https://search.dev.ndltd.org/etd/uwo/oai:uwo.scholaris.ca:20.500.14721/32490","repository":{"repo_id":"uwo","name":"Western University","base_url":"https://uwo.scholaris.ca/server/oai/request"},"display":{"title":"Absence of Enhancer of Zeste Homolog 2 Promotes the Progression of KRAS-Driven Pancreatic Ductal Adenocarcinoma","abstract":"Pancreatic ductal adenocarcinoma (PDAC) is estimated to be the second deadliest cancer by 2030. Previous studies showed constitutive activation of KRAS (KRASG12D) is a key genetic driver of PDAC, accelerated by deletion of the epigenetic regulator Enhancer of Zeste Homologue 2 (EZH2). However, contradictory findings suggest multiple roles for EZH2. The goal of this study was to define EZH2’s contributes to early KRASG12D-driven PDAC. I hypothesized that EZH2 restricts KRASG12D initiation of PDAC in response to injury. To address this hypothesis, genetically modified mice with targeted deletion of the SET domain of Ezh2 +/- KRASG12D were exposed to cerulein-induced pancreatic injury and examined for pancreatic lesions. Histological analysis for markers of tissue damage and inflammation showed loss of EZH2 caused no difference in the pre-neoplastic lesion formation but did affect progression, and reduced immune cell infiltration, suggesting a role for EZH2 in limiting early progression of KRASG12D-mediated PDAC.","abstract_html":"Pancreatic ductal adenocarcinoma (PDAC) is estimated to be the second deadliest cancer by 2030. Previous studies showed constitutive activation of KRAS (KRASG12D) is a key genetic driver of PDAC, accelerated by deletion of the epigenetic regulator Enhancer of Zeste Homologue 2 (EZH2). However, contradictory findings suggest multiple roles for EZH2. The goal of this study was to define EZH2’s contributes to early KRASG12D-driven PDAC. I hypothesized that EZH2 restricts KRASG12D initiation of PDAC in response to injury. To address this hypothesis, genetically modified mice with targeted deletion of the SET domain of Ezh2 +/- KRASG12D were exposed to cerulein-induced pancreatic injury and examined for pancreatic lesions. Histological analysis for markers of tissue damage and inflammation showed loss of EZH2 caused no difference in the pre-neoplastic lesion formation but did affect progression, and reduced immune cell infiltration, suggesting a role for EZH2 in limiting early progression of KRASG12D-mediated PDAC.","abstract_has_math":false,"creators":["Wang, Xiaoyi"],"institution":"The University of Western Ontario","degree_name":"M Sc","degree_level":null,"degree_discipline":"Physiology and Pharmacology","degree_department":null,"school":null,"contributors":[],"advisors":["Christopher Pin"],"committee_chairs":[],"committee_members":[],"year":2022,"date_issued":"2022-09-29","date_published":"2022-09-29","updated_at":"2026-07-27T21:56:16Z","subjects":["PDAC","EZH2","KRAS","pancreatitis."],"languages":["en_ca"],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"https://hdl.handle.net/20.500.14721/32490","outbound_label":"Handle","outbound_source":"dc:identifier.uri"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor.advisor","label":"Advisor","values":["Christopher Pin"]},{"key":"dc:creator","label":"Author","values":["Wang, Xiaoyi"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.accessioned","label":"Dc Date Accessioned","values":["2025-07-10T19:31:21Z"]},{"key":"dc:date.available","label":"Dc Date Available","values":["2025-07-10T19:31:21Z"]},{"key":"dc:date.issued","label":"Date","values":["2022-09-29"]},{"key":"dc:publisher","label":"Institution","values":["The University of Western Ontario"]},{"key":"dc:type","label":"Dc Type","values":["thesis"]},{"key":"thesis:degree_discipline","label":"Discipline","values":["Physiology and Pharmacology"]},{"key":"thesis:degree_name","label":"Degree Name","values":["M Sc"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["PDAC","EZH2","KRAS","pancreatitis."]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language.iso","label":"Language (ISO)","values":["en_ca"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier.uri","label":"Identifier URI","values":["https://hdl.handle.net/20.500.14721/32490"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["The thesis cover page in the PDF document includes references to Western University’s previous institutional repository platform, known as Scholarship@Western, and links to that platform (beginning with ir.lib.uwo.ca). In citing or referring to this thesis, use the DOI or handle from this page instead. Sample citation: Author name, \"Thesis title.\" (Year). Western University Open Repository. https://doi.org/10.71858/123456."]},{"key":"dc:description.abstract","label":"Abstract","values":["Pancreatic ductal adenocarcinoma (PDAC) is estimated to be the second deadliest cancer by 2030. Previous studies showed constitutive activation of KRAS (KRASG12D) is a key genetic driver of PDAC, accelerated by deletion of the epigenetic regulator Enhancer of Zeste Homologue 2 (EZH2). However, contradictory findings suggest multiple roles for EZH2. The goal of this study was to define EZH2’s contributes to early KRASG12D-driven PDAC. I hypothesized that EZH2 restricts KRASG12D initiation of PDAC in response to injury. To address this hypothesis, genetically modified mice with targeted deletion of the SET domain of Ezh2 +/- KRASG12D were exposed to cerulein-induced pancreatic injury and examined for pancreatic lesions. Histological analysis for markers of tissue damage and inflammation showed loss of EZH2 caused no difference in the pre-neoplastic lesion formation but did affect progression, and reduced immune cell infiltration, suggesting a role for EZH2 in limiting early progression of KRASG12D-mediated PDAC."]},{"key":"dc:title","label":"Title","values":["Absence of Enhancer of Zeste Homolog 2 Promotes the Progression of KRAS-Driven Pancreatic Ductal Adenocarcinoma"]}]}],"canonical_facts":{"dc:contributor.advisor":["Christopher Pin"],"dc:creator":["Wang, Xiaoyi"],"dc:date.accessioned":["2025-07-10T19:31:21Z"],"dc:date.available":["2025-07-10T19:31:21Z"],"dc:date.issued":["2022-09-29"],"dc:description":["The thesis cover page in the PDF document includes references to Western University’s previous institutional repository platform, known as Scholarship@Western, and links to that platform (beginning with ir.lib.uwo.ca). In citing or referring to this thesis, use the DOI or handle from this page instead. Sample citation: Author name, \"Thesis title.\" (Year). Western University Open Repository. https://doi.org/10.71858/123456."],"dc:description.abstract":["Pancreatic ductal adenocarcinoma (PDAC) is estimated to be the second deadliest cancer by 2030. Previous studies showed constitutive activation of KRAS (KRASG12D) is a key genetic driver of PDAC, accelerated by deletion of the epigenetic regulator Enhancer of Zeste Homologue 2 (EZH2). However, contradictory findings suggest multiple roles for EZH2. The goal of this study was to define EZH2’s contributes to early KRASG12D-driven PDAC. I hypothesized that EZH2 restricts KRASG12D initiation of PDAC in response to injury. To address this hypothesis, genetically modified mice with targeted deletion of the SET domain of Ezh2 +/- KRASG12D were exposed to cerulein-induced pancreatic injury and examined for pancreatic lesions. Histological analysis for markers of tissue damage and inflammation showed loss of EZH2 caused no difference in the pre-neoplastic lesion formation but did affect progression, and reduced immune cell infiltration, suggesting a role for EZH2 in limiting early progression of KRASG12D-mediated PDAC."],"dc:identifier.uri":["https://hdl.handle.net/20.500.14721/32490"],"dc:language.iso":["en_ca"],"dc:publisher":["The University of Western Ontario"],"dc:subject":["PDAC","EZH2","KRAS","pancreatitis."],"dc:title":["Absence of Enhancer of Zeste Homolog 2 Promotes the Progression of KRAS-Driven Pancreatic Ductal Adenocarcinoma"],"dc:type":["thesis"],"thesis:degree_discipline":["Physiology and Pharmacology"],"thesis:degree_name":["M Sc"]},"updated_at":"2026-07-27T21:56:16Z"}