# The Unfolded Protein Response in Glioblastoma

> **NIH NIH F30** · CASE WESTERN RESERVE UNIVERSITY · 2020 · $50,520

## Abstract

PROJECT SUMMARY
Glioblastoma is highly resistant to chemo- and radiotherapy. Despite treatment, median survival is only 12-15
months. Tumor cells rely upon elevated stress response pathways to survive and maintain a rapid proliferative
rate in the harsh tumor microenvironment. Glioblastoma stem cells (GSCs) are particularly enriched in their ability
to survive in the context of nutrient deprivation, high reactive oxygen species, DNA damage and radiation.
Upregulation of heat shock proteins (HSPs) and the unfolded proteins response (UPR) promote cell survival
during stress. These pathways are elevated in glioblastoma and knockdown induces chemosensitivity and cell
death. The UPR specifically relieves ER stress, a key pathway of radiation-induced cell death. I have identified
RSAD1 as a potential regulator of the UPR and thus a novel dependency in GSCs. There are currently no
published studies characterizing the function of RSAD1. RSAD1 is upregulated in glioblastoma and is correlated
with worse survival, and my preliminary evidence demonstrates that RSAD1 knockdown significantly impairs
proliferation in GSCs. I found that RSAD1 binding partners enrich for UPR regulators and HSPs. The goal of this
research is to test the hypothesis that RSAD1 promotes survival in GSCs through activation of the UPR. Given
the important role of the UPR in inducing stress resilience, inhibition of RSAD may act as a chemo- or
radiosensitizer of GSCs, in addition to independently impairing proliferation. RSAD1 may therefore be a novel
target for synergistic therapy in glioblastoma.

## Key facts

- **NIH application ID:** 9898337
- **Project number:** 5F30CA217066-05
- **Recipient organization:** CASE WESTERN RESERVE UNIVERSITY
- **Principal Investigator:** Briana Prager
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $50,520
- **Award type:** 5
- **Project period:** 2017-08-01 → 2021-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9898337

## Citation

> US National Institutes of Health, RePORTER application 9898337, The Unfolded Protein Response in Glioblastoma (5F30CA217066-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9898337. Licensed CC0.

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