Biomedical Sciences ETDs

Publication Date

Spring 5-12-2025

Abstract

Glioblastomas (GBMs) are the most aggressive primary brain tumors, and despite over 50 years of research efforts, the median survival remains at 14 months post-diagnosis. The current standard of care consists of maximal surgical resection radiotherapy with concurrent chemotherapy using temozolomide. However, the highly proliferative and invasive nature of GBM cells renders total resection nearly impossible as tumor cells invade the surrounding healthy tissue. The molecular and environmental drivers of these tumorigenic phenotypes are largely unknown. Here, we demonstrate that the neurodevelopmental transcription factor ASCL1 enhances tumor cell proliferation and invasion while activating the expression of a neural stem cell gene signature. Similarly, alcohol exposure during early glioma development promotes increased invasion as well as angiogenesis within the tumor and decreases the survival of male mice. Together, these findings indicate that dysregulation of ASCL1 drives the tumorigenic phenotypes that impede therapeutic efficacy and alcohol consumption augments early tumor progression and increases mortality in a sex-specific manner.

Keywords

Glioma, Transcription factors, Neuro-oncology, alcohol

Document Type

Dissertation

Language

English

Degree Name

Biomedical Sciences

Level of Degree

Doctoral

Department Name

Biomedical Sciences Graduate Program

First Committee Member (Chair)

Judy L Cannon

Second Committee Member

Tou Yia Vue

Third Committee Member

Sara G M Piccirillo

Fourth Committee Member

Nora Perrone Bizzozero

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