# Uncovering Therapeutic Targets in Pediatric High Grade Gliomas with the H3K27M Mutation

> **NIH NIH K08** · MAYO CLINIC ROCHESTER · 2020 · $183,141

## Abstract

Project Summary
In children, tumors affecting the brain result in more cancer-related deaths than any other type of tumor. It is
thus critical to identify new therapies. Among pediatric patients, one of the most devastating brain tumor types
is Diffuse Intrinsic Pontine Gliomas (DIPG). Our understanding of this deadly disease has recently been
advanced by important discoveries, including the finding that the majority of DIPG tumors harbor the histone
H3K27M mutation. This mutation results in global hypomethylation of H3K27 residues and is the pathological
hallmark for this disease.
The applicant has discovered that Wnt5a and STAT3 signaling are critically important for proliferation and
survival of H3K27M tumors and inhibiting these pathways restores the reduced H3K27 methylation patterns
and leads to tumor cell death. This project aims to further understand how STAT3 is critical for H3K27M
tumors and validate STAT3 as a drug target in DIPG tumors. A further goal is to develop additional pediatric
patient derived high grade glioma xenografts and cell lines. These techniques will be generalizable to other
molecular drivers of tumorigenesis in malignant brain tumors. The proposed research is significant because it
is expected to vertically advance therapeutic options for treating DIPG tumors.
The candidate is an MD/PhD trained neurosurgeon-scientist with advanced clinical training in pediatric brain
tumors whose career goal is to advance treatment strategies for malignant brain tumors through basic and
translational research. The career development plan and research will be mentored by Dr. Jann Sarkaria, a
physician-scientist whose research goals are in alignment with the candidate. This proposal combines the
strengths of the candidate, the mentors, and the research institution in order to provide an opportunity for the
candidate to become a successful independent neurosurgeon-scientist.

## Key facts

- **NIH application ID:** 10000178
- **Project number:** 5K08NS092891-04
- **Recipient organization:** MAYO CLINIC ROCHESTER
- **Principal Investigator:** David Daniels
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $183,141
- **Award type:** 5
- **Project period:** 2017-09-01 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10000178

## Citation

> US National Institutes of Health, RePORTER application 10000178, Uncovering Therapeutic Targets in Pediatric High Grade Gliomas with the H3K27M Mutation (5K08NS092891-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10000178. Licensed CC0.

---

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