Pediatric osteosarcoma tumors are characterized by an unusual abundance of grossly dilated endoplasmic reticulum and an immense genomic instability that has complicated identifying new effective molecular therapeutic targets. Here we report a novel molecular signature that encompasses the majority of 108 patient tumor samples, PDXs and osteosarcoma cell lines. These tumors exhibit reduced expression of four critical COPII vesicle proteins that has resulted in the accumulation of procollagen-I protein within ‘hallmark’ dilated ER. Using CRISPR activation technology, increased expression of only SAR1A and SEC24D to physiologically normal levels was sufficient to restore both collagen-I secretion and resolve dilated ER morphology to normal.
","abstract_html":"<p>Pediatric osteosarcoma tumors are characterized by an unusual abundance of grossly dilated endoplasmic reticulum and an immense genomic instability that has complicated identifying new effective molecular therapeutic targets. Here we report a novel molecular signature that encompasses the majority of 108 patient tumor samples, PDXs and osteosarcoma cell lines. These tumors exhibit reduced expression of four critical COPII vesicle proteins that has resulted in the accumulation of procollagen-I protein within ‘hallmark’ dilated ER. Using CRISPR activation technology, increased expression of only SAR1A and SEC24D to physiologically normal levels was sufficient to restore both collagen-I secretion and resolve dilated ER morphology to normal. </p>","abstract_has_math":false,"creators":["Wood, Rachael"],"institution":null,"degree_name":"Doctor of Philosophy (PhD)","degree_level":"Dissertation","degree_discipline":"Biomedical Sciences","degree_department":null,"school":null,"contributors":["Linda M. Hendershot, PhD"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2021,"date_issued":"2021-12-01T08:00:00Z","date_published":"2021-12-01T08:00:00Z","updated_at":"2026-07-24T05:00:45Z","subjects":["COPII; CRISPR activation","endoplasmic reticulum","osteosarcoma","procollagen","Analytical, Diagnostic and Therapeutic Techniques and Equipment","Disease Modeling","Diseases","Genetic Structures","Investigative Techniques","Medical Cell Biology","Medical Genetics","Medical Molecular Biology","Medical Sciences","Medicine and Health Sciences","Neoplasms","Pediatrics"],"languages":[],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"https://dc.uthsc.edu/dissertations/573","outbound_label":"Repository record","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Linda M. Hendershot, PhD"]},{"key":"dc:creator","label":"Author","values":["Wood, Rachael"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.available","label":"Dc Date Available","values":["2022-06-08T07:00:00Z"]},{"key":"thesis:degree_discipline","label":"Discipline","values":["Biomedical Sciences"]},{"key":"thesis:degree_level","label":"Degree Level","values":["Dissertation"]},{"key":"thesis:degree_name","label":"Degree Name","values":["Doctor of Philosophy (PhD)"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["COPII; CRISPR activation","endoplasmic reticulum","osteosarcoma","procollagen","Analytical, Diagnostic and Therapeutic Techniques and Equipment","Disease Modeling","Diseases","Genetic Structures","Investigative Techniques","Medical Cell Biology","Medical Genetics","Medical Molecular Biology","Medical Sciences","Medicine and Health Sciences","Neoplasms","Pediatrics"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["https://dc.uthsc.edu/dissertations/573"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["Pediatric osteosarcoma tumors are characterized by an unusual abundance of grossly dilated endoplasmic reticulum and an immense genomic instability that has complicated identifying new effective molecular therapeutic targets. Here we report a novel molecular signature that encompasses the majority of 108 patient tumor samples, PDXs and osteosarcoma cell lines. These tumors exhibit reduced expression of four critical COPII vesicle proteins that has resulted in the accumulation of procollagen-I protein within ‘hallmark’ dilated ER. Using CRISPR activation technology, increased expression of only SAR1A and SEC24D to physiologically normal levels was sufficient to restore both collagen-I secretion and resolve dilated ER morphology to normal.
"]},{"key":"dc:title","label":"Title","values":["Identifying the Molecular Cause of Extreme Endoplasmic Reticulum Dilation in Pediatric Osteosarcoma and Its Relationship to the Disease"]}]}],"canonical_facts":{"dc:contributor":["Linda M. Hendershot, PhD"],"dc:creator":["Wood, Rachael"],"dc:date.available":["2022-06-08T07:00:00Z"],"dc:description.abstract":["Pediatric osteosarcoma tumors are characterized by an unusual abundance of grossly dilated endoplasmic reticulum and an immense genomic instability that has complicated identifying new effective molecular therapeutic targets. Here we report a novel molecular signature that encompasses the majority of 108 patient tumor samples, PDXs and osteosarcoma cell lines. These tumors exhibit reduced expression of four critical COPII vesicle proteins that has resulted in the accumulation of procollagen-I protein within ‘hallmark’ dilated ER. Using CRISPR activation technology, increased expression of only SAR1A and SEC24D to physiologically normal levels was sufficient to restore both collagen-I secretion and resolve dilated ER morphology to normal.
"],"dc:identifier":["https://dc.uthsc.edu/dissertations/573"],"dc:subject":["COPII; CRISPR activation","endoplasmic reticulum","osteosarcoma","procollagen","Analytical, Diagnostic and Therapeutic Techniques and Equipment","Disease Modeling","Diseases","Genetic Structures","Investigative Techniques","Medical Cell Biology","Medical Genetics","Medical Molecular Biology","Medical Sciences","Medicine and Health Sciences","Neoplasms","Pediatrics"],"dc:title":["Identifying the Molecular Cause of Extreme Endoplasmic Reticulum Dilation in Pediatric Osteosarcoma and Its Relationship to the Disease"],"thesis:degree_discipline":["Biomedical Sciences"],"thesis:degree_level":["Dissertation"],"thesis:degree_name":["Doctor of Philosophy (PhD)"]},"updated_at":"2026-07-24T05:00:45Z"}