# Regulation of glioblastoma cells by GABAergic neurons in human organoid-tumor chimeras

> **NIH NIH R21** · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · 2024 · $170,988

## Abstract

PROJECT SUMMARY/ABSTRACT
Glioblastoma (GBM, WHO Grade IV glioma) is one of the most common and deadliest primary brain tumors that
affects both children and adults. GBM is associated with significantly elevated mortality, and there are no
effective therapies available for patients despite many previous clinical trials. It is believed that a better
understanding of the cell types and factors regulating GBM cell properties in the brain could provide novel
insights into the pathology and reveal new therapeutic targets for treating GBM patients. The main goal of this
R21 proposal is to elucidate the role of human GABAergic neurons in regulating the proliferation and survival of
GBM cells in the brain using an innovative co-culture approach of human GBM spheroids and human induced
pluripotent stem cell (iPSC)-derived telencephalic organoids (organoid-GBM chimera). To achieve this goal, we
will use the most advanced neuroscience tools and techniques, including human stem cell-derived brain
organoids, optogenetics, rabies virus tracing, and single-cell RNA sequencing, to characterize the
communication between GABAergic neurons and tumor cells in organoid-GBM chimera and the effects of this
communication on tumor cell survival and proliferation. Our specific hypothesis is that GABAergic neurons form
functional synapses with tumor cells in GBM-organoid chimeras to promote tumor cell proliferation or survival
via GABA-mediated depolarization of tumor cells. The specific aims to test this hypothesis are (1) to determine
whether GABAergic neurons establish functional synapses with GBM cells to regulate tumor growth and survival
and (2) to determine the role of trans-synaptic signaling proteins in regulating tumor growth and survival. Overall,
we expect that this study will advance our understanding of the cellular and molecular mechanisms involved in
the regulation of GBM cell properties in the human brain and provide a novel framework for studying the
interactions of human brain tumors with human neurons in a human brain-like environment.

## Key facts

- **NIH application ID:** 10823304
- **Project number:** 5R21CA279773-02
- **Recipient organization:** UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH
- **Principal Investigator:** Oleksandr Shcheglovitov
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $170,988
- **Award type:** 5
- **Project period:** 2023-04-06 → 2025-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10823304

## Citation

> US National Institutes of Health, RePORTER application 10823304, Regulation of glioblastoma cells by GABAergic neurons in human organoid-tumor chimeras (5R21CA279773-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10823304. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*