# Mechanisms of SOX2 Regulation in Glioblastoma

> **NIH NIH R01** · WASHINGTON UNIVERSITY · 2024 · $378,290

## Abstract

ABSTRACT
Glioblastoma (GB), the most common malignant primary brain tumor in adults, is invariably fatal. Thus, there is
an urgent need to discover new and meaningful therapeutic strategies for this lethal disease. A major reason for
our current lack of effective therapies is the extensive genetic and epigenetic heterogeneity of GB tumors. Within
the epigenetic diversity of GB cells, accumulating evidence has now firmly established the existence of a clinically
important subpopulation of GB cancer cells, called GB stem cells (GSCs), which represents a key cellular
substrate for treatment resistance and disease recurrence. Thus, targeting the GSC pool in tumors is an
important conceptual strategy, which has the potential to generate novel, durable treatments. We and others
have previously shown that the pluripotency-related transcription factor SOX2 plays a critical role in the
expression of malignant GSC phenotypes, including self-renewal capacity, invasiveness, and in vivo tumor
growth. Remarkably, despite the significant genetic heterogeneity between tumors, SOX2 is expressed in almost
all GB tumor cells, including GSCs, implicating this transcription factor as a common epigenetic driver in GB.
Thus, the identification of the mechanisms that regulate SOX2 function in GSCs will not only advance our
knowledge about the fundamental biology of SOX2 in the clinically relevant GSC subpopulation but also lead to
the discovery of SOX2-dependent therapeutic targets that may be effective across different GB tumors and cell
types. Based on published work and preliminary data, we will examine two key mechanisms controlling the SOX2
program in GSCs: post-translational control of SOX2 stability (Aim 1) and specification of SOX2 target gene
expression through local and long-range chromatin interactions (Aim 2). To study these mechanisms, we will
take advantage of two complementary human model systems: a well-characterized library of patient tumor-
derived GSCs and a novel, isogenic, human neural stem cell-based GSC model with defined genetic mutations.
The long-term goal of this project is to develop novel SOX2-directed therapeutic strategies to disrupt malignant
tumor growth and amplify the efficacy of current treatments.

## Key facts

- **NIH application ID:** 10900702
- **Project number:** 5R01NS128470-03
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Albert Hong-Jae Kim
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $378,290
- **Award type:** 5
- **Project period:** 2022-08-15 → 2027-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10900702

## Citation

> US National Institutes of Health, RePORTER application 10900702, Mechanisms of SOX2 Regulation in Glioblastoma (5R01NS128470-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10900702. Licensed CC0.

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