# Regulation of Cell Fate and Treatment Response in WNT Medulloblastoma

> **NIH NIH P01** · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · 2021 · $256,216

## Abstract

ABSTRACT
We have identified mutations in the X-linked, RNA helicase DDX3X as the second most frequent mutation in
medulloblastoma (MB). We now show that DDX3X: (i) orchestrates normal hindbrain patterning and
development; (ii) suppresses the initiation of Wnt and Shh MB; (iii) restricts the susceptibility of specific NPCs to
generate these tumors; and (iv) serves as a `rheostat' in the stress response, regulating global patterns of gene
transcription and translation and live-die `decisions. Our studies also helped explain why WNT-MBs are
eminently curable. We showed that paracrine signals driven by mutant CTNNB1 in WNT-MB disrupts the blood
brain barrier (BBB), permitting the accumulation of high levels of intra-tumoral chemotherapy and a robust
therapeutic response. Here, we will continue our focus on WNT-MB to address three new Specific Aims that will:
determine how DDX3X regulates cell fate decisions in the normal and malignant hindbrain; generate novel
immunotherapies of WNT MB; and translate new treatments of WNT MB to clinical trial.

## Key facts

- **NIH application ID:** 10270675
- **Project number:** 2P01CA096832-16A1
- **Recipient organization:** ST. JUDE CHILDREN'S RESEARCH HOSPITAL
- **Principal Investigator:** Richard Gilbertson
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $256,216
- **Award type:** 2
- **Project period:** 2003-04-01 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10270675

## Citation

> US National Institutes of Health, RePORTER application 10270675, Regulation of Cell Fate and Treatment Response in WNT Medulloblastoma (2P01CA096832-16A1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10270675. Licensed CC0.

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