{"id":{"repo_id":"uiuc","oai_identifier":"oai:www.ideals.illinois.edu:2142/115568"},"canonical_url":"https://search.dev.ndltd.org/etd/uiuc/oai:www.ideals.illinois.edu:2142/115568","repository":{"repo_id":"uiuc","name":"University of Illinois - Urbana-Champaign","base_url":"https://www.ideals.illinois.edu/oai-pmh"},"display":{"title":"Deconstructing the influences of combinatorial microenvironmental cues on human non-parenchymal liver cells in models of liver fibrosis","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":["Brougham-Cook, Aidan James"],"institution":"University of Illinois at Urbana-Champaign","degree_name":"Ph.D.","degree_level":"Dissertation","degree_discipline":"Bioengineering","degree_department":null,"school":null,"contributors":["Underhill, Gregory H","Perez-Pinera, Pablo","Harley, Brendan","Khetani, Salman R"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2022,"date_issued":"2022-05","date_published":"2022-05","updated_at":"2026-07-22T22:24:54Z","subjects":["ECM","Stiffness","soluble factors","HSC","LSEC","high-throughput","microenvironment"],"languages":["en","eng"],"rights":["Copyright 2022 Aidan Brougham-Cook"],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"https://hdl.handle.net/2142/115568","outbound_label":"Handle","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Underhill, Gregory H","Perez-Pinera, Pablo","Harley, Brendan","Khetani, Salman R"]},{"key":"dc:creator","label":"Author","values":["Brougham-Cook, Aidan James"]}]},{"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":["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":["ECM","Stiffness","soluble factors","HSC","LSEC","high-throughput","microenvironment"]}]},{"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 Aidan Brougham-Cook"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["https://hdl.handle.net/2142/115568"]}]},{"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, Aidan Brougham-Cook, accepted the attached license on 2022-04-18 at 13:14.","The student, Aidan Brougham-Cook, submitted this Dissertation for approval on 2022-04-18 at 13:20.","This Dissertation was approved for publication on 2022-04-21 at 16:58.","DSpace SAF Submission Ingestion Package generated from Vireo submission #17752 on 2022-11-11 at 12:06:03","Liver disease is a major public health concern, and one of the key sources of tissue and organ dysregulation in liver disease is the onset of fibrosis. Liver fibrosis produces changes in the composition of the liver and has profound repercussions for cell behavior and function, especially in tissue microenvironments. The makeup and configuration of the microenvironment is critical in directing cell behaviors due to the myriad extracellular cues it presents. Cellular microarray technology is a powerful platform for efficiently and robustly dissecting the effects of multiple microenvironmental parameters simultaneously. In this dissertation, I describe the use of high-throughput cellular microarrays to investigate the role of combinatorial microenvironments in regulating the phenotypes of two important cell types of the liver, hepatic stellate cells (HSCs) and liver sinusoidal endothelial cells (LSECs), in models of liver fibrosis. We discovered that these cells are highly sensitive to microenvironmental context, and in testing various combinations of extracellular matrix (ECM) proteins, substrate stiffness, and soluble factors, we revealed and characterized previously undescribed patterns and trends in HSC and LSEC phenotype plasticity and heterogeneity. We also demonstrated that HSC-LSEC interactions are regulated by microenvironmental context and present a new framework for understanding how these cells respond to each other and their microenvironments in fibrosis. Taken together, these findings will assist with development of therapeutics for liver fibrosis and deepen our knowledge and understanding of fundamental cell biology in healthy and fibrotic livers."]},{"key":"dc:format","label":"Dc Format","values":["application/pdf"]},{"key":"dc:title","label":"Title","values":["Deconstructing the influences of combinatorial microenvironmental cues on human non-parenchymal liver cells in models of liver fibrosis"]}]}],"canonical_facts":{"dc:contributor":["Underhill, Gregory H","Perez-Pinera, Pablo","Harley, Brendan","Khetani, Salman R"],"dc:creator":["Brougham-Cook, Aidan James"],"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, Aidan Brougham-Cook, accepted the attached license on 2022-04-18 at 13:14.","The student, Aidan Brougham-Cook, submitted this Dissertation for approval on 2022-04-18 at 13:20.","This Dissertation was approved for publication on 2022-04-21 at 16:58.","DSpace SAF Submission Ingestion Package generated from Vireo submission #17752 on 2022-11-11 at 12:06:03","Liver disease is a major public health concern, and one of the key sources of tissue and organ dysregulation in liver disease is the onset of fibrosis. Liver fibrosis produces changes in the composition of the liver and has profound repercussions for cell behavior and function, especially in tissue microenvironments. The makeup and configuration of the microenvironment is critical in directing cell behaviors due to the myriad extracellular cues it presents. Cellular microarray technology is a powerful platform for efficiently and robustly dissecting the effects of multiple microenvironmental parameters simultaneously. In this dissertation, I describe the use of high-throughput cellular microarrays to investigate the role of combinatorial microenvironments in regulating the phenotypes of two important cell types of the liver, hepatic stellate cells (HSCs) and liver sinusoidal endothelial cells (LSECs), in models of liver fibrosis. We discovered that these cells are highly sensitive to microenvironmental context, and in testing various combinations of extracellular matrix (ECM) proteins, substrate stiffness, and soluble factors, we revealed and characterized previously undescribed patterns and trends in HSC and LSEC phenotype plasticity and heterogeneity. We also demonstrated that HSC-LSEC interactions are regulated by microenvironmental context and present a new framework for understanding how these cells respond to each other and their microenvironments in fibrosis. Taken together, these findings will assist with development of therapeutics for liver fibrosis and deepen our knowledge and understanding of fundamental cell biology in healthy and fibrotic livers."],"dc:format":["application/pdf"],"dc:identifier":["https://hdl.handle.net/2142/115568"],"dc:language":["en","eng"],"dc:rights":["Copyright 2022 Aidan Brougham-Cook"],"dc:subject":["ECM","Stiffness","soluble factors","HSC","LSEC","high-throughput","microenvironment"],"dc:title":["Deconstructing the influences of combinatorial microenvironmental cues on human non-parenchymal liver cells in models of liver fibrosis"],"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"}