# Glioma Circuitry: Bridging Systems Neuroscience and Cancer

> **NIH NIH DP1** · STANFORD UNIVERSITY · 2021 · $56,720

## Abstract

Project Summary
DP1 NS111132 original summary:
High-grade gliomas such as glioblastoma and diffuse intrinsic pontine glioma (DIPG) are among the most
intractable human cancers. These tumors are quick to recur and nearly impossible to eliminate, and as such
represent the leading cause brain cancer-related death in both children and adults. A fundamental shift in our
approach to glioma therapy is in dire need. My research group has recently discovered that gliomas grow in
response to nervous system activity (Venkatesh et al., 2015, Cell). We initially conceptualized this discovery in
the framework of neuronal activity-regulated molecular factors released into the tumor microenvironment.
While brain activity-regulated growth factor secretion is certainly part of the picture, it is insufficient to explain
the striking magnitude of the effect, nor the apparent dependency of glioma on these neuronal mechanisms
(Venkatesh et al., 2017, Nature). Our cellular and molecular work has led us to the startling realization that
gliomas functionally integrate into electrically active neuronal circuits through bona fide neuron to glioma
synapses, and the effects of neuron – glioma signaling may be amplified throughout the tumor via a network of
recently described glioma to glioma gap junction-mediated connections (Osswald et al., 2015, Nature). We
hypothesize that this cooperative interconnected network of glioma cells and neurons is fundamental to high-
grade glioma progression and therapy resistance. Effective therapy for this lethal group of brain cancers may
therefore require targeting not only molecular mechanisms of cell proliferation and survival, but also patterns of
membrane depolarization and structural connections between cells. In order to study this, a shift from the
predominant cellular/molecular perspective of cancer biology to a systems neuroscience approach is required.

## Key facts

- **NIH application ID:** 10302769
- **Project number:** 3DP1NS111132-03S1
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** Michelle Monje-Deisseroth
- **Activity code:** DP1 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $56,720
- **Award type:** 3
- **Project period:** 2021-01-15 → 2022-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10302769

## Citation

> US National Institutes of Health, RePORTER application 10302769, Glioma Circuitry: Bridging Systems Neuroscience and Cancer (3DP1NS111132-03S1). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10302769. Licensed CC0.

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