# Dissecting the cooperation of FOXR2 and ETS transcription factors in FOXR2-expressing diffuse midline gliomas

> **NIH NIH K08** · CHILDREN'S HOSPITAL OF LOS ANGELES · 2024 · $262,863

## Abstract

PROJECT SUMMARY
Diffuse midline gliomas (DMGs) are devastating childhood brain tumors for which there are no effective
therapies. While histone mutations are thought to be a critical tumor initiating event, they are insufficient for
glioma formation and co-occur with somatic alterations in other pathways, including MYC and growth factor
receptor signaling. I have recently discovered that a subset of DMGs aberrantly express the forkhead
transcription factor FOXR2. FOXR2 is sufficient to enhance DMG formation and also required for FOXR2-
expressing DMGs. FOXR2 DNA-binding is highly enriched at E26 transformation-specific (ETS) motifs, and
FOXR2 specifically activates ETS transcriptional circuits. Moreover, FOXR2-expressing DMGs lack
amplifications and genetic events in growth factor receptor pathways, suggesting functional redundancy. Indeed,
phosphoproteomic evidence shows that FOXR2-expressing cells activate MAPK signaling. These findings
provide the rationale to study how aberrant FOXR2 expression cooperates with ETS transcription factors to
enhance DMG formation by activating downstream pathways, including MAPK signaling. To advance our
understanding of FOXR2-expressing DMGs, this proposal will pursue the following two Specific Aims: 1) Test
the hypothesis that ETS transcription factors are required for FOXR2-mediated oncogenesis and 2) Test the
hypothesis that the oncogenic phenotype of FOXR2 is mediated through MAPK signaling.
 I am currently an Instructor in Pediatrics and a Pediatric Neuro-Oncologist at Dana-Farber Cancer Institute
with 80% of my time protected for research. I am fully committed to a career as a physician-scientist, with the
goal of elucidating DMG disease mechanisms to advance patient care. The purpose of this career development
award is to fill a critical gap in my training and enable me to gain specific skills in in vivo animal modeling of
pediatric brain tumors and high-throughput genetic perturbation approaches. I have chosen an outstanding
mentorship team, Dr. Pratiti Bandopadhayay and Dr. Myles Brown. Dr. Bandopadhayay is an established leader
in pediatric brain tumor genomics, and Dr. Brown is an international leader in epigenomics and chromatin biology
with extensive experience in mentoring physician-scientists. My scientific advisory committee includes experts
reflecting key areas of my training plan: Drs. Eric Fischer (proteomics), Timothy Phoenix (murine glioma models),
Keith Ligon (immunohistochemical analyses of murine models), and Kim Stegmaier (pediatric cancer genomics
and high-throughput genetic perturbation assays). I will moreover collaborate with Dr. John Doench (high-
throughput genetic perturbation methods and analyses) to gain expertise. Under the mentorship of my co-
mentors and the commitment of my scientific advisory committee, I will train in the stimulating environments of
Dana-Farber Cancer Institute and the Broad Institute, both outstanding institutions with tremendous resources.
The K08 award...

## Key facts

- **NIH application ID:** 10807829
- **Project number:** 1K08CA279908-01A1
- **Recipient organization:** CHILDREN'S HOSPITAL OF LOS ANGELES
- **Principal Investigator:** Jessica Whei Tsai
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $262,863
- **Award type:** 1
- **Project period:** 2024-08-15 → 2029-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10807829

## Citation

> US National Institutes of Health, RePORTER application 10807829, Dissecting the cooperation of FOXR2 and ETS transcription factors in FOXR2-expressing diffuse midline gliomas (1K08CA279908-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10807829. Licensed CC0.

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