{"id":{"repo_id":"buffalo","oai_identifier":"oai:ubir.buffalo.edu:10477/79324"},"canonical_url":"https://search.dev.ndltd.org/etd/buffalo/oai:ubir.buffalo.edu:10477/79324","repository":{"repo_id":"buffalo","name":"Buffalo","base_url":"https://ubir.buffalo.edu/oai/request"},"display":{"title":"Megalin, Cubilin, and FcRn Expression in Type 2 Diabetes: Implications for Pharmaceutics and Diabetic Kidney Disease","abstract":"Ph.D.","abstract_html":"Ph.D.","abstract_has_math":false,"creators":["Bryniarski, Mark"],"institution":"State University of New York at Buffalo","degree_name":null,"degree_level":null,"degree_discipline":null,"degree_department":null,"school":null,"contributors":["Morris, Marilyn","Pharmaceutical Sciences"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2019,"date_issued":"2019-04-04T19:47:09Z","date_published":"2019-04-04T19:47:09Z","updated_at":"2026-07-27T19:05:14Z","subjects":["pharmaceutical sciences"],"languages":["eng"],"rights":["Users of works found in University at Buffalo Institutional Repository (UBIR) are responsible for identifying and contacting the copyright owner for permission to reuse. University at Buffalo Libraries do not manage rights for copyright-protected works and cannot assist with permissions.","Copyright retained by author."],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"http://hdl.handle.net/10477/79324","outbound_label":"Handle","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Morris, Marilyn","Pharmaceutical Sciences"]},{"key":"dc:creator","label":"Author","values":["Bryniarski, Mark"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2019-04-04T19:47:09Z","2019","2019-01-17 12:28:00"]},{"key":"dc:publisher","label":"Institution","values":["State University of New York at Buffalo"]},{"key":"dc:type","label":"Dc Type","values":["Text","Dissertation"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["pharmaceutical sciences"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language","label":"Dc Language","values":["eng"]},{"key":"dc:rights","label":"Dc Rights","values":["Users of works found in University at Buffalo Institutional Repository (UBIR) are responsible for identifying and contacting the copyright owner for permission to reuse. University at Buffalo Libraries do not manage rights for copyright-protected works and cannot assist with permissions.","Copyright retained by author."]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["http://hdl.handle.net/10477/79324"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["Ph.D.","Monoclonal antibodies (mAbs) continue to lead protein therapeutics. However, very few studies have examined the impact of diabetes mellitus (DM), one of the most frequent disease states worldwide, on mAb disposition. Previous work from our lab identified DM-associated increases in both the total and renal clearances of administered human IgG, which was utilized to represent the isotype most commonly used for therapeutic antibodies. The overall goal of the current work was to begin to elucidate the potential mechanisms contributing to these increased clearances in DM. Beginning with total clearance, two potential mechanism were proposed: increased enzymatic activity and decreased expression of the IgG-recycling protein FcRn in DM. To address the first objective, a method was attempted to detect the catabolism of unlabeled IgG in frozen tissue homogenates. The end goal was to use this as a foundation to then measure catabolism of fluorescently-labeled mAbs in DM and non-DM tissue samples. However, the lack of any detectable IgG catabolism in three separate tissue types, with multiple revisions to the method, resulted in aborting this project goal. To address the second aim, a disease progression study was conducted in the Zucker diabetic fatty (ZDF) rat model of type 2 DM (T2DM). Three groups were present: lean control, untreated ZDF, and ZDF treated with the antidiabetic drug pioglitazone. Renal and hepatic FcRn were then examined at varying disease stages. No change in renal cortex FcRn expression was detected at any age. In contrast, FcRn protein expression decreased in untreated ZDF rat livers at all ages. To our knowledge, this marks the first time decreased FcRn expression has ever been measured in any form of DM. The ensuing thesis project represents a combined effort spanning multiple disciplines and collaborations to provide novel insight into several aspects of both nephrology and protein therapeutics. The immediate impact remains unknown, but will hopefully be resolved through the numerous projects stemming from the current work."]},{"key":"dc:format","label":"Dc Format","values":["application/pdf"]},{"key":"dc:title","label":"Title","values":["Megalin, Cubilin, and FcRn Expression in Type 2 Diabetes: Implications for Pharmaceutics and Diabetic Kidney Disease"]}]}],"canonical_facts":{"dc:contributor":["Morris, Marilyn","Pharmaceutical Sciences"],"dc:creator":["Bryniarski, Mark"],"dc:date":["2019-04-04T19:47:09Z","2019","2019-01-17 12:28:00"],"dc:description":["Ph.D.","Monoclonal antibodies (mAbs) continue to lead protein therapeutics. However, very few studies have examined the impact of diabetes mellitus (DM), one of the most frequent disease states worldwide, on mAb disposition. Previous work from our lab identified DM-associated increases in both the total and renal clearances of administered human IgG, which was utilized to represent the isotype most commonly used for therapeutic antibodies. The overall goal of the current work was to begin to elucidate the potential mechanisms contributing to these increased clearances in DM. Beginning with total clearance, two potential mechanism were proposed: increased enzymatic activity and decreased expression of the IgG-recycling protein FcRn in DM. To address the first objective, a method was attempted to detect the catabolism of unlabeled IgG in frozen tissue homogenates. The end goal was to use this as a foundation to then measure catabolism of fluorescently-labeled mAbs in DM and non-DM tissue samples. However, the lack of any detectable IgG catabolism in three separate tissue types, with multiple revisions to the method, resulted in aborting this project goal. To address the second aim, a disease progression study was conducted in the Zucker diabetic fatty (ZDF) rat model of type 2 DM (T2DM). Three groups were present: lean control, untreated ZDF, and ZDF treated with the antidiabetic drug pioglitazone. Renal and hepatic FcRn were then examined at varying disease stages. No change in renal cortex FcRn expression was detected at any age. In contrast, FcRn protein expression decreased in untreated ZDF rat livers at all ages. To our knowledge, this marks the first time decreased FcRn expression has ever been measured in any form of DM. The ensuing thesis project represents a combined effort spanning multiple disciplines and collaborations to provide novel insight into several aspects of both nephrology and protein therapeutics. The immediate impact remains unknown, but will hopefully be resolved through the numerous projects stemming from the current work."],"dc:format":["application/pdf"],"dc:identifier":["http://hdl.handle.net/10477/79324"],"dc:language":["eng"],"dc:publisher":["State University of New York at Buffalo"],"dc:rights":["Users of works found in University at Buffalo Institutional Repository (UBIR) are responsible for identifying and contacting the copyright owner for permission to reuse. University at Buffalo Libraries do not manage rights for copyright-protected works and cannot assist with permissions.","Copyright retained by author."],"dc:subject":["pharmaceutical sciences"],"dc:title":["Megalin, Cubilin, and FcRn Expression in Type 2 Diabetes: Implications for Pharmaceutics and Diabetic Kidney Disease"],"dc:type":["Text","Dissertation"]},"updated_at":"2026-07-27T19:05:14Z"}