# Epigenetic Control and Genome Organization

> **NIH NIH P01** · UNIVERSITY OF VERMONT & ST AGRIC COLLEGE · 2021 · $1,678,923

## Abstract

OVERALL PROGRAM SUMMARY
 Gary Stein and Janet Stein, Program Directors
Our Program Project is a thematically, experimentally and operationally integrated multidisciplinary team
approach to address key components of genome organization that are functionally linked to modified epigenetic
control of gene expression in breast cancer. The thematic focus and working hypothesis of our Program is
that genomic organization and epigenetic control of gene expression coordinately facilitate
physiological regulation, including hormone responsiveness, of normal and cancer cell growth,
proliferation and cell identity. Our highly collaborative research team established paradigm-shifting insights
into parameters of nuclear organization that include: 1. Mitotic gene bookmarking by phenotypic transcription
factors to control fidelity of gene expression as cells divide; 2. Relationships between fidelity of nuclear
organization, transcription factor localization and metastasis of breast cancer to bone; 3. Dynamic modifications
of higher-order inter- and intra-chromosomal interactions in breast cancer cells; 4. Coordinate control of cell
growth and phenotype by tissue-specific transcription factors; 5. Epitranscriptomic profiling of endocrine therapy
resistant and advanced breast cancer cells in response to selective estrogen receptor modulators; and 6.
Noncoding RNA-mediated regulation of the aggressive breast cancer phenotype.
This application captures the scientific progress, synergy and momentum of our research team and leverages
powerful new technologies for editing the genome, visualizing cells at super resolution and in real time, and
decoding higher-order genome organization. We will use normal mammary epithelial, subtype-specific and
endocrine resistant breast cancer cell models for discovery, then validate key findings and examine potential
clinical relevance using animal models, public databases and patient tumor specimens and organoids.
Emphasis will be on exploring molecular mechanisms that integrate multiple dimensions of epigenetic control
with modified genome organization in breast cancer. Each of the three projects focuses on a unique aspect of
epigenetic control that is required for fidelity of gene expression and is compromised in breast cancer, including:
the pivotal role of mitotic gene bookmarking in stabilizing the normal mammary epithelial phenotype (Project 1);
novel functions of bromodomain chromatin readers in endocrine therapy resistance (Project 2); and contributions
of the novel long noncoding RNA MANCR to deregulated genome organization in aggressive breast cancer
(Project 3). A shared resource core will support integrated bioinformatics and biostatistics analyses; standardized
experimental design; cell, organoid and in vivo models; and resource authentication to ensure scientific rigor and
reproducibility. An administrative core will maximize scientific and programmatic integration, prioritization and
oversight. The impact of this progr...

## Key facts

- **NIH application ID:** 10107340
- **Project number:** 1P01CA240685-01A1
- **Recipient organization:** UNIVERSITY OF VERMONT & ST AGRIC COLLEGE
- **Principal Investigator:** Gary S. Stein
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $1,678,923
- **Award type:** 1
- **Project period:** 2021-04-01 → 2026-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10107340

## Citation

> US National Institutes of Health, RePORTER application 10107340, Epigenetic Control and Genome Organization (1P01CA240685-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10107340. Licensed CC0.

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