# Diversity supplement to P01CA240685 to characterize bromodomain proteins associated with endocrine therapy resistance in breast cancer

> **NIH NIH P01** · UNIVERSITY OF VERMONT & ST AGRIC COLLEGE · 2024 · $70,497

## Abstract

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 program will be the integratio...

## Key facts

- **NIH application ID:** 11035920
- **Project number:** 3P01CA240685-04S1
- **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:** 2024
- **Award amount:** $70,497
- **Award type:** 3
- **Project period:** 2021-04-01 → 2025-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11035920

## Citation

> US National Institutes of Health, RePORTER application 11035920, Diversity supplement to P01CA240685 to characterize bromodomain proteins associated with endocrine therapy resistance in breast cancer (3P01CA240685-04S1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/11035920. Licensed CC0.

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