Identifying the Molecular Cause of Extreme Endoplasmic Reticulum Dilation in Pediatric Osteosarcoma and Its Relationship to the Disease

<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>

Name thesis:degree_name

Doctor of Philosophy (PhD)

Level thesis:degree_level

Dissertation

Discipline thesis:degree_discipline

Biomedical Sciences

Year dc:date.available

2021

Author dc:creator

• Wood, Rachael

Contributors dc:contributor

• Linda M. Hendershot, PhD

• 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

Repository record dc:identifier

https://dc.uthsc.edu/dissertations/573

OAI identifier oai:identifier

oai:dc.uthsc.edu:dissertations-1573