{"id":{"repo_id":"uiuc","oai_identifier":"oai:www.ideals.illinois.edu:2142/127438"},"canonical_url":"https://search.dev.ndltd.org/etd/uiuc/oai:www.ideals.illinois.edu:2142/127438","repository":{"repo_id":"uiuc","name":"University of Illinois - Urbana-Champaign","base_url":"https://www.ideals.illinois.edu/oai-pmh"},"display":{"title":"Mechanisms by which 27-hydroxycholesterol modulates the secretion of extracellular vesicles","abstract":"Submission published under a 24 month embargo labeled 'Closed Access', the embargo will last until 2026-12-01","abstract_html":"Submission published under a 24 month embargo labeled 'Closed Access', the embargo will last until 2026-12-01","abstract_has_math":false,"creators":["Das Gupta, Anasuya"],"institution":"University of Illinois at Urbana-Champaign","degree_name":"Ph.D.","degree_level":"Dissertation","degree_discipline":"Molecular & Integrative Physi","degree_department":null,"school":null,"contributors":["Nelson, Erik R","Bagchi, Milan K","Boppart, Stephen A","Boppart, Marni D"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2024,"date_issued":"2024-09-17","date_published":"2024-09-17","updated_at":"2026-07-22T22:25:04Z","subjects":["Reactive Oxygen Species","Mitochondria","27-hydroxycholesterol","Extracellular Vesicles","Myeloid Immune Cell","Lysosome"],"languages":["en","eng"],"rights":["Copyright 2024 Anasuya Das Gupta"],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"https://hdl.handle.net/2142/127438","outbound_label":"Handle","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Nelson, Erik R","Bagchi, Milan K","Boppart, Stephen A","Boppart, Marni D"]},{"key":"dc:creator","label":"Author","values":["Das Gupta, Anasuya"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2024-09-17","2024-12"]},{"key":"dc:type","label":"Dc Type","values":["text","Thesis"]},{"key":"thesis:degree_discipline","label":"Discipline","values":["Molecular & Integrative Physi"]},{"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":["Reactive Oxygen Species","Mitochondria","27-hydroxycholesterol","Extracellular Vesicles","Myeloid Immune Cell","Lysosome"]}]},{"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 2024 Anasuya Das Gupta"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["https://hdl.handle.net/2142/127438"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["Submission published under a 24 month embargo labeled 'Closed Access', the embargo will last until 2026-12-01","The student, Anasuya Das Gupta, accepted the attached license on 2024-09-09 at 09:23.","The student, Anasuya Das Gupta, submitted this Dissertation for approval on 2024-09-09 at 09:30.","This Dissertation was approved for publication on 2024-09-17 at 14:38.","DSpace SAF Submission Ingestion Package generated from Vireo submission #21219 on 2025-03-28 at 14:53:18","Breast cancer remains a global health concern, necessitating the need for continued research in understanding the pathways involved in its progression and in developing new and more targeted therapeutic strategies. Elevated circulating cholesterol has been associated with breast cancer recurrence in pre-clinical as well as clinical models. The cholesterol metabolite, 27-hydroxycholesterol (27HC), has been identified to establish an immunosuppressive tumor microenvironment) in myeloid immune cells. Interestingly, 27HC treatment of different myeloid immune cells results in increased secretion of extracellular vesicles (EVs) with altered cargo. EVs serve as crucial mediators of cell-to-cell communication in normal physiology as well as in diseased states and have been largely studied in regard to their role in cancer progression. However, the mechanisms by which their biogenesis and secretion are regulated by metabolic or endocrine factors remain unknown. Here, we delineate a mechanism by which EV secretion is regulated by 27HC, where treatment of myeloid immune cells (RAW 264.7 and J774A.1) with 27HC impairs lysosomal homeostasis, leading to shunting of multivesicular bodies (MVBs) away from lysosomal degradation, towards secretion as EVs. This altered lysosomal function is likely caused by mitochondrial dysfunction and subsequent increase in reactive oxygen species (ROS). Interestingly, cotreatment with a mitochondria-targeted antioxidant rescued the lysosomal impairment and attenuated the 27HC-mediated increase in EV secretion. Overall, our findings establish how a cholesterol metabolite regulates EV secretion and paves the way for the development of strategies to regulate cancer progression by controlling EV secretion."]},{"key":"dc:format","label":"Dc Format","values":["application/pdf"]},{"key":"dc:title","label":"Title","values":["Mechanisms by which 27-hydroxycholesterol modulates the secretion of extracellular vesicles"]}]}],"canonical_facts":{"dc:contributor":["Nelson, Erik R","Bagchi, Milan K","Boppart, Stephen A","Boppart, Marni D"],"dc:creator":["Das Gupta, Anasuya"],"dc:date":["2024-09-17","2024-12"],"dc:description":["Submission published under a 24 month embargo labeled 'Closed Access', the embargo will last until 2026-12-01","The student, Anasuya Das Gupta, accepted the attached license on 2024-09-09 at 09:23.","The student, Anasuya Das Gupta, submitted this Dissertation for approval on 2024-09-09 at 09:30.","This Dissertation was approved for publication on 2024-09-17 at 14:38.","DSpace SAF Submission Ingestion Package generated from Vireo submission #21219 on 2025-03-28 at 14:53:18","Breast cancer remains a global health concern, necessitating the need for continued research in understanding the pathways involved in its progression and in developing new and more targeted therapeutic strategies. Elevated circulating cholesterol has been associated with breast cancer recurrence in pre-clinical as well as clinical models. The cholesterol metabolite, 27-hydroxycholesterol (27HC), has been identified to establish an immunosuppressive tumor microenvironment) in myeloid immune cells. Interestingly, 27HC treatment of different myeloid immune cells results in increased secretion of extracellular vesicles (EVs) with altered cargo. EVs serve as crucial mediators of cell-to-cell communication in normal physiology as well as in diseased states and have been largely studied in regard to their role in cancer progression. However, the mechanisms by which their biogenesis and secretion are regulated by metabolic or endocrine factors remain unknown. Here, we delineate a mechanism by which EV secretion is regulated by 27HC, where treatment of myeloid immune cells (RAW 264.7 and J774A.1) with 27HC impairs lysosomal homeostasis, leading to shunting of multivesicular bodies (MVBs) away from lysosomal degradation, towards secretion as EVs. This altered lysosomal function is likely caused by mitochondrial dysfunction and subsequent increase in reactive oxygen species (ROS). Interestingly, cotreatment with a mitochondria-targeted antioxidant rescued the lysosomal impairment and attenuated the 27HC-mediated increase in EV secretion. Overall, our findings establish how a cholesterol metabolite regulates EV secretion and paves the way for the development of strategies to regulate cancer progression by controlling EV secretion."],"dc:format":["application/pdf"],"dc:identifier":["https://hdl.handle.net/2142/127438"],"dc:language":["en","eng"],"dc:rights":["Copyright 2024 Anasuya Das Gupta"],"dc:subject":["Reactive Oxygen Species","Mitochondria","27-hydroxycholesterol","Extracellular Vesicles","Myeloid Immune Cell","Lysosome"],"dc:title":["Mechanisms by which 27-hydroxycholesterol modulates the secretion of extracellular vesicles"],"dc:type":["text","Thesis"],"thesis:degree_discipline":["Molecular & Integrative Physi"],"thesis:degree_level":["Dissertation"],"thesis:degree_name":["Ph.D."],"thesis:institution_name":["University of Illinois at Urbana-Champaign"]},"updated_at":"2026-07-22T22:25:04Z"}