# p52 induces mesenchymal differentiation in glioblastoma

> **NIH NIH F32** · UNIVERSITY OF CHICAGO · 2021 · $64,802

## Abstract

PROJECT SUMMARY/ABSTRACT
The goal of this project is to examine the role of p52, one of the five nuclear factor-kB (NF-kB) subunits, in
regulating mesenchymal (MES) transformation in glioblastoma (GBM). GBM is the most common primary glial
neoplasm in adults and, despite aggressive multimodal therapy, is nearly universally fatal. The classification of
GBM into molecular subtypes based on gene expression profiles has revealed several regulatory pathways
critical to GBM pathogenesis. Recently, NF-kB was identified as a master regulator of the highly aggressive
MES GBM subtype. The central hypothesis of our work is that p52 induces MES transformation in GBM and
that modulation of this p52-specific pathway alters the tumor microenvironment (TME) and affects the efficacy
of anti-GBM therapy. Our aims examine sequential aspects of the mechanism by which p52 directs subtype
differentiation to uncover novel strategies to improve the treatment of this devastating disease. In Aim 1, we
examine the effects of p52 modulation on subtype transformation. Another known master regulator of MES
differentiation, Stat3, plays a critical role in promoting p52 formation. We will examine the hypothesis that
Stat3-mediated MES differentiation occurs through regulation of p52 production. Additionally, as NF-kB is a
transcription factor that modulates gene expression, we will examine the downstream profile affected by
differential p52 promoter binding through genome-wide target-identification to elucidate potential targets critical
to MES transformation. As transformation between subtypes is dependent not only on cell-intrinsic signaling
pathways, but also on cell-extrinsic changes, in Aim 2 we will investigate the impact of modulating p52 on the
TME and on GBM treatment efficacy. Specifically, we will alter p52 expression in an immunocompetent murine
GBM model and test the hypothesis that p52 modulation alters the TME and affects the response to adjuvant
therapy. These complimentary aims will define the role of p52 in MES transformation in GBM. From a broader
perspective, the results of the current project will expand our understanding of GBM molecular subclass
transformation and potentially lead to the identification of novel targets that can enhance anti-GBM therapy and
improve patient survival.

## Key facts

- **NIH application ID:** 9959180
- **Project number:** 5F32CA232643-02
- **Recipient organization:** UNIVERSITY OF CHICAGO
- **Principal Investigator:** David J Voce
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $64,802
- **Award type:** 5
- **Project period:** 2019-05-15 → 2022-05-14

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9959180

## Citation

> US National Institutes of Health, RePORTER application 9959180, p52 induces mesenchymal differentiation in glioblastoma (5F32CA232643-02). Retrieved via AI Analytics 2026-06-11 from https://api.ai-analytics.org/grant/nih/9959180. Licensed CC0.

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