# Epigenetic regulation of LDOC1 drives tumor biology in high risk ependymoma

> **NIH NIH R01** · UNIVERSITY OF COLORADO DENVER · 2023 · $348,592

## Abstract

PROJECT SUMMARY
Brain tumors have become the leading cause of cancer-related death in children. Ependymoma (EPN)
accounts for a substantial number of these deaths. Over 70% of children presenting with ependymoma will
relapse and almost all children who relapse will eventually die. Unlike medulloblastoma, no effective
chemotherapy has been developed in ependymoma to complement the standard, and eventually for most
ineffectual, surgery and radiation. In particular, children with the most common type of ependymoma,
posterior fossa Group A (PFA1), relapse more frequently and experience more invasive, metastatic disease at
relapse. Thus, there is a critical need for more effective therapies to combat high-risk PFA1 tumors. Single-cell
RNAsequencing data suggest that the epigenetic silencing of LDOC1 within a specific subpopulation of tumor
cells has a profound, direct impact on the tumor biology of PFA1 tumors. The driving hypothesis is that
epigenetic silencing of LDOC1 with in the MEC subpopulation, as a result of chromatin remodeling, is the
molecular driver in PFA1 EPN, through upregulation of non-canoncial NF-B activation. To address this
hypothesis, the studies in aim one will determine the role of LDOC1 expression in EPN by examining 1) the
mechanism of gene silencing, 2) the functional role of loss of LDOC1 in vitro and in vivo, and 3) the genomic
transcriptional targets of LDOC1. Aim two is designed to 1) determine how LDOC1 regulates non-canoncial
NF-B signaling and 2) identify the functional consequences of the NF-B signaling pathway. The collective
proposed studies will define the effect of LDOC1 loss, which we hypothesize to be the molecular driver of
tumor biology of PFA1 EPN. These studies will significantly add to our understanding of childhood EPN and
have the potential to identify rational therapeutic targets for children with this high-risk, poor-outcome pediatric
brain tumor.

## Key facts

- **NIH application ID:** 10623262
- **Project number:** 5R01CA239302-04
- **Recipient organization:** UNIVERSITY OF COLORADO DENVER
- **Principal Investigator:** NICHOLAS K FOREMAN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $348,592
- **Award type:** 5
- **Project period:** 2020-07-01 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10623262

## Citation

> US National Institutes of Health, RePORTER application 10623262, Epigenetic regulation of LDOC1 drives tumor biology in high risk ependymoma (5R01CA239302-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10623262. Licensed CC0.

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