# Mechanism of regulation of progenitor proliferation and transformation

> **NIH NIH R01** · ADVANCED SCIENCE RESEARCH CENTER · 2020 · $174,032

## Abstract

Glioblastomas (GBM) are highly aggressive and incurable primary brain tumors, with a median survival of little
more than a year. Expression profiling and whole genome sequencing from hundreds of human glioma
specimens have revealed a broad spectrum of genetic alterations and identified four major expression
signatures, including a pattern of expression that is highly enriched in oligodendrocyte lineage genes, which is
also characterized by mutations in the tumor suppressor p53. During the previous funding period we focused
on the molecular mechanisms regulating proliferation and gene expression in oligodendrocyte progenitor cells,
with an emphasis on E2F1 and Myc as transcription factors and recruiters of epigenetic modulators of lysine
residues on nucleosomal histone H3. This renewal focuses on a novel histone modification (symmetric arginine
methylation catalyzed by PRMT5), which we define as critical for oligodendrocyte progenitor (OPC)
differentiation. Since PRMT5 is upregulated in glioma, and its expression levels negatively correlate with
patients' survival, it represents a very attractive therapeutic target. Based on our proteomic and transcriptomic
datasets we propose that a better understanding of its molecular mechanism of action would shed important
light on mechanisms of OPC differentiation in physiological conditions and of transformation into proneural
gliomas. We anticipate that the results of the proposed experimental plan will enhance the current knowledge
of OPC population dynamic, while impacting a better understanding of the process of glial transformation and
suggesting novel therapeutic targets. The overall goal is to characterize PRMT5 molecular partners and
mechanism of action in normal OPCs under physiological conditions and in transformed OPCs at different
stages of glioma progression, address its function in the presence or absence of p53 and evaluate the potential
therapeutic value of PRMT5 inhibition in gliomas.

## Key facts

- **NIH application ID:** 10016389
- **Project number:** 5R01NS052738-14
- **Recipient organization:** ADVANCED SCIENCE RESEARCH CENTER
- **Principal Investigator:** Peter Canoll
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $174,032
- **Award type:** 5
- **Project period:** 2017-09-01 → 2021-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10016389

## Citation

> US National Institutes of Health, RePORTER application 10016389, Mechanism of regulation of progenitor proliferation and transformation (5R01NS052738-14). Retrieved via AI Analytics 2026-05-29 from https://api.ai-analytics.org/grant/nih/10016389. Licensed CC0.

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