Date of Award

Spring 2025

Degree Type

Thesis

Department

Biological Sciences

Director of Thesis

Dr. Deepak Bhere

Second Reader

Dr. Kandy Velazquez

Abstract

Glioblastoma (GBM), a World Health Organization Grade IV brain tumor, remains one of the most aggressive and treatment-resistant malignancies. It is characterized by rapid proliferation, deep infiltration, and a high level of genotypic and phenotypic heterogeneity. Despite advancements in medical technology and neuro-oncology, GBM remains one of the most treatment-resistant cancers with a median survival rate of only nine months post-diagnosis and less than 5% of patients surviving beyond 5 years of diagnosis. The standard treatment constitutes maximum surgical resection followed by chemotherapy and radiation. These therapeutic strategies are blocked by significant challenges like the blood-brain barrier (BBB), and intratumoral heterogeneity. These factors promote poor outcomes and help underscore the need for novel and more effective therapeutic approaches.

This study aims to develop and validate GBM organoid models to assess the efficacy of novel therapeutics. Organoids are three-dimensional cell cultures which better mimic the in vivo tumor microenvironment compared to traditional 2D monolayer cell cultures, offering an improved model for evaluating treatment response and resistance mechanisms. Using a GBM cell line, we will generate organoids and characterize them using imaging techniques. The therapeutic agent in question is microRNA-124 (miR-124), a small non-coding RNA known to be a key regulator of microglial growth.

The efficacy of these treatments will be assessed via cell viability assays and Western blotting to evaluate pathway modulation. By establishing a robust organoid model for GBM, this research aims to enhance preclinical drug testing, paving the way for improved therapeutic strategies and informing future in vivo studies.

First Page

1

Last Page

37

Rights

© 2025, Dev P. Patel

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