# Leveraging multi-omics to define the role of epigenetic regulation by PRC2 in Esthesioneuroblastoma

> **NIH NIH F30** · DUKE UNIVERSITY · 2024 · $35,073

## Abstract

ABSTRACT
Permanent smell loss is a common morbidity associated with esthesioneuroblastoma (ENB), a tumor thought to
arise from the olfactory epithelium in the nose. This is due to necessity for bulk surgical resection, regardless of
tumor grade. As such, the development of novel medical treatment strategies is necessary to preserve olfaction
in this patient population. The olfactory epithelium is a neurogenic niche that produces neurons and supporting
epithelial cells throughout life, and various undifferentiated stages of normal epithelial proliferation and
development have been observed in ENB. The epigenetic regulator polycomb repressive complex 2 (PRC2) has
been implicated in driving proliferative cell states in stem cell niches throughout the body. We have shown that
PRC2 is crucial for basal cell proliferation in the olfactory epithelium, and we have identified that it is expressed
in proliferating cells in ENB. Because ENB is a rare tumor, mechanistic biological studies are sparse, and no cell
lines or mouse models exist. Furthermore, the majority of ENBs do not share common driver mutations,
emphasizing the importance of epigenetic regulation. Here I propose to utilize newly-developed multi-omic
studies to investigate how PRC2 expression in human ENB specifies cellular states and contributes to tumor
growth. I will perform single cell chromatin and transcriptomic assays on multiple tumors to identify areas of
chromosomal accessibility. Furthermore, I will use pharmacologic assays in human ENB samples to assess the
downstream effects on transcription. Finally, spatial transcriptomics will be used to define ENB cellular and
molecular composition, including PRC-associated expression, and how this compares to normal olfactory
epithelium, to elucidate cellular signaling dynamics among tumor and immune cells within the ENB
microenvironment. Completion of the proposed studies will define epigenetic drivers co-opted by ENB with the
goal of identifying new druggable targets, allowing for improved survival and preservation of smell. Altogether,
the research and training plan outlined in this proposal combined with expert mentorship from Dr. Bradley
Goldstein will prepare me with the rigorous training necessary for a successful career as a surgeon-scientist in
rhinology and anterior skull base surgery.

## Key facts

- **NIH application ID:** 10834078
- **Project number:** 5F30DC021348-02
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** John Barratt Finlay
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $35,073
- **Award type:** 5
- **Project period:** 2023-08-01 → 2025-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10834078

## Citation

> US National Institutes of Health, RePORTER application 10834078, Leveraging multi-omics to define the role of epigenetic regulation by PRC2 in Esthesioneuroblastoma (5F30DC021348-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10834078. Licensed CC0.

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