{"id":{"repo_id":"uiuc","oai_identifier":"oai:www.ideals.illinois.edu:2142/115508"},"canonical_url":"https://search.dev.ndltd.org/etd/uiuc/oai:www.ideals.illinois.edu:2142/115508","repository":{"repo_id":"uiuc","name":"University of Illinois - Urbana-Champaign","base_url":"https://www.ideals.illinois.edu/oai-pmh"},"display":{"title":"Characterizing the anti-angiogenic resistance potential of cross-family PDGF:VEGFR2 interactions in glioblastoma","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":["Castleberry, Colin"],"institution":"University of Illinois at Urbana-Champaign","degree_name":"Ph.D.","degree_level":"Dissertation","degree_discipline":"Bioengineering","degree_department":null,"school":null,"contributors":["Imoukhuede, Princess I","Amos, Jennifer","Jensen, Paul","Dobrucki, Wawrzyniec","Chen, Jie"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2022,"date_issued":"2022-05","date_published":"2022-05","updated_at":"2026-07-22T22:24:54Z","subjects":["RTK","VEGF","PDGF","cross-family signaling","cell signaling","cancer","angiogenesis","computational modeling","mass action kinetics","global sensitivity analysis","structural alignment","meta-analysis","glioblastoma","growth factors"],"languages":["en","eng"],"rights":["Copyright by Colin Castleberry 2022. All Rights Reserved."],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"https://hdl.handle.net/2142/115508","outbound_label":"Handle","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Imoukhuede, Princess I","Amos, Jennifer","Jensen, Paul","Dobrucki, Wawrzyniec","Chen, Jie"]},{"key":"dc:creator","label":"Author","values":["Castleberry, Colin"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2022-05","2022-03-24"]},{"key":"dc:type","label":"Dc Type","values":["text","Thesis"]},{"key":"thesis:degree_discipline","label":"Discipline","values":["Bioengineering"]},{"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":["RTK","VEGF","PDGF","cross-family signaling","cell signaling","cancer","angiogenesis","computational modeling","mass action kinetics","global sensitivity analysis","structural alignment","meta-analysis","glioblastoma","growth factors"]}]},{"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 by Colin Castleberry 2022. All Rights Reserved."]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["https://hdl.handle.net/2142/115508"]}]},{"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, Colin Castleberry, accepted the attached license on 2022-03-16 at 14:11.","The student, Colin Castleberry, submitted this Dissertation for approval on 2022-03-16 at 14:12.","This Dissertation was approved for publication on 2022-03-24 at 15:12.","DSpace SAF Submission Ingestion Package generated from Vireo submission #17505 on 2022-11-11 at 11:55:45","Glioblastoma is the most common and lethal primary brain tumor in adults. Anti-angiogenic treatment has shown positive results in improving GBM patient survival. Bevacizumab, a drug that sequesters the angiogenic growth factor, VEGF-A, has been approved by the FDA for use in GBM patients and moderately improves patient survival; however, these GBM bevacizumab responders eventually acquire bevacizumab resistance. New approaches must be pursued to understand anti-VEGF resistance in GBM. The involvement of other signaling axes potentially explains anti-VEGF failings. PDGF:VEGFR2 interactions were recently discovered and prior computational modeling predicts that PDGF:VEGFR2 interactions could constitute a large proportion of VEGFR2-ligand complexes in certain physiological and breast cancer conditions. Under PDGF:VEGFR2 cross-family signaling, upregulated PDGFs would directly activate VEGFRs and lead to anti-VEGF therapy resistance. We aimed to use computational tools to assess how strongly PDGFs can affect VEGFR occupancy in GBM, and to assess the potential of PDGF:VEGFR2 interactions as resistance mechanisms for anti-VEGF treatment in GBM. However, the GBM ligand and receptor parameter space has not been established such that a GBM condition can be computationally modelled, and an analysis platform has not yet been developed to assess the ability of cross-family PDGF ligands to control VEGFR-occupancy in relation to canonical VEGF-family ligands in pathology. These challenges have been addressed in two ways: (1) I created and analyze a toolbox of computational models to compare PDGF:VEGFR2 interactions with canonical VEGF:VEGFR interactions across several mechanistic differences and assumptions in angiogenic signaling, and (2) I performed an in-depth meta-analysis of GBM growth factors, including: VEGF-A, Ang-2, PDGF-BB, FGF-2, EGF, PlGF, and IGF in order to better characterize the GBM growth factor landscape, and to consolidate concentration data for the ligands aiding tumor growth and angiogenesis."]},{"key":"dc:format","label":"Dc Format","values":["application/pdf"]},{"key":"dc:title","label":"Title","values":["Characterizing the anti-angiogenic resistance potential of cross-family PDGF:VEGFR2 interactions in glioblastoma"]}]}],"canonical_facts":{"dc:contributor":["Imoukhuede, Princess I","Amos, Jennifer","Jensen, Paul","Dobrucki, Wawrzyniec","Chen, Jie"],"dc:creator":["Castleberry, Colin"],"dc:date":["2022-05","2022-03-24"],"dc:description":["Submission published under a 24 month embargo labeled 'U of I Access', the embargo will last until 2024-05-01","The student, Colin Castleberry, accepted the attached license on 2022-03-16 at 14:11.","The student, Colin Castleberry, submitted this Dissertation for approval on 2022-03-16 at 14:12.","This Dissertation was approved for publication on 2022-03-24 at 15:12.","DSpace SAF Submission Ingestion Package generated from Vireo submission #17505 on 2022-11-11 at 11:55:45","Glioblastoma is the most common and lethal primary brain tumor in adults. Anti-angiogenic treatment has shown positive results in improving GBM patient survival. Bevacizumab, a drug that sequesters the angiogenic growth factor, VEGF-A, has been approved by the FDA for use in GBM patients and moderately improves patient survival; however, these GBM bevacizumab responders eventually acquire bevacizumab resistance. New approaches must be pursued to understand anti-VEGF resistance in GBM. The involvement of other signaling axes potentially explains anti-VEGF failings. PDGF:VEGFR2 interactions were recently discovered and prior computational modeling predicts that PDGF:VEGFR2 interactions could constitute a large proportion of VEGFR2-ligand complexes in certain physiological and breast cancer conditions. Under PDGF:VEGFR2 cross-family signaling, upregulated PDGFs would directly activate VEGFRs and lead to anti-VEGF therapy resistance. We aimed to use computational tools to assess how strongly PDGFs can affect VEGFR occupancy in GBM, and to assess the potential of PDGF:VEGFR2 interactions as resistance mechanisms for anti-VEGF treatment in GBM. However, the GBM ligand and receptor parameter space has not been established such that a GBM condition can be computationally modelled, and an analysis platform has not yet been developed to assess the ability of cross-family PDGF ligands to control VEGFR-occupancy in relation to canonical VEGF-family ligands in pathology. These challenges have been addressed in two ways: (1) I created and analyze a toolbox of computational models to compare PDGF:VEGFR2 interactions with canonical VEGF:VEGFR interactions across several mechanistic differences and assumptions in angiogenic signaling, and (2) I performed an in-depth meta-analysis of GBM growth factors, including: VEGF-A, Ang-2, PDGF-BB, FGF-2, EGF, PlGF, and IGF in order to better characterize the GBM growth factor landscape, and to consolidate concentration data for the ligands aiding tumor growth and angiogenesis."],"dc:format":["application/pdf"],"dc:identifier":["https://hdl.handle.net/2142/115508"],"dc:language":["en","eng"],"dc:rights":["Copyright by Colin Castleberry 2022. All Rights Reserved."],"dc:subject":["RTK","VEGF","PDGF","cross-family signaling","cell signaling","cancer","angiogenesis","computational modeling","mass action kinetics","global sensitivity analysis","structural alignment","meta-analysis","glioblastoma","growth factors"],"dc:title":["Characterizing the anti-angiogenic resistance potential of cross-family PDGF:VEGFR2 interactions in glioblastoma"],"dc:type":["text","Thesis"],"thesis:degree_discipline":["Bioengineering"],"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"}