# (PQ1) Identifying and targeting human glioblastoma migrating in the peritumoral niche

> **NIH NIH R01** · STANFORD UNIVERSITY · 2021 · $359,783

## Abstract

Glioblastoma, the most common and deadly primary brain tumor, disseminates widely throughout the brain by
hijacking the cell migration pathways used by normal neural stem cells. Migrating glioblastoma persist in the
surrounding brain (pre-malignant field) after tumor resection, ultimately recurring and killing the patient.
Glioblastoma migration is the hallmark of this devastating disease, yet no one has isolated and analyzed the
single cell transcriptome of migrating glioblastoma as compared to normal (mature and fetal) or peritumoral
astrocytes. We propose that migrating glioblastoma and peritumoral astrocytes employ fetal astrocyte
genes to promote glioblastoma migration, that these genes are consistent within and across patients,
and that inhibition of these genes will halt glioblastoma migration. To deconstruct and target glioblastoma
migrating within the human peritumoral astrocyte microniche and suggest personalized therapies for patients,
we have developed three innovative methods that leverage primary human tissue. Aim 1: To determine the
extent to which migrating glioblastoma are defined by human fetal astrocyte gene expression, distinct
from normal and glioblastoma astrocytes. Single cell isolation, RNA-seq, and transcriptome analysis of
matched human glioblastoma, peritumoral, and normal brain will be used to identify brain cellular subtypes and
migrating glioblastoma within the peritumoral brain. Migrating glioblastoma genetic markers that overlap with
fetal astrocyte genes and are consistent within and across samples will be further validated. Aim 2: To test
the extent to which peritumoral astrocytes facilitate glioblastoma migration through fetal astrocyte
gene expression. Matched human glioblastoma and peritumoral astrocytes, isolated from fresh surgical
specimens through our novel immunopanning separation technique, will undergo RNA-seq and culture. We
suspect transcriptional and functional similarities between peritumoral astrocytes and normal fetal astrocytes.
Candidate pathways will be promoted or inhibited in transwell migration assays using primary human
glioblastoma. Aim 3: To test whether glioblastoma migration can be inhibited through knockdown of
either fetal astrocyte genes in migrating glioblastoma or peritumoral astrocytes. Candidate genes
identified in migrating glioblastoma (Aim 1) and peritumoral astrocytes (Aim 2) hold therapeutic promise, and
will first be validated using primary human glioblastoma in vitro and ex vivo. Targets showing promise in these
validation studies of either migrating glioblastoma or peritumoral astrocytes will undergo human glioblastoma-
in-mouse intracranial xenograft modeling. Control and primary specimens will be imaged with CLARITY to
confirm the dynamic glioblastoma-peritumoral astrocyte interactions. This project has direct translational
potential as targeting glioblastoma migration will confine glioblastoma to a local disease, improving response to
surgical resection and radiation b...

## Key facts

- **NIH application ID:** 10146964
- **Project number:** 5R01CA216054-05
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** Melanie Hayden Gephart
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $359,783
- **Award type:** 5
- **Project period:** 2017-04-01 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10146964

## Citation

> US National Institutes of Health, RePORTER application 10146964, (PQ1) Identifying and targeting human glioblastoma migrating in the peritumoral niche (5R01CA216054-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10146964. Licensed CC0.

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