# Nuclear Receptor Regulation of Epigenetics in Endocrine-Related Cancers

> **NIH NIH F99** · UNIVERSITY OF VERMONT & ST AGRIC COLLEGE · 2020 · $29,892

## Abstract

Project Summary/Abstract:
A major contributor to altered gene expression and chromatin reorganization in endocrine-related cancers is
nuclear receptor signaling. Nuclear hormone receptors (NRs) are ligand-activated transcription factors that
regulate diverse physiological functions including development, reproduction, homeostasis, and metabolism.
They also represent an important group of prognostic indicators and therapeutic targets in hormone-driven
cancers.
In the F99 phase of this proposal, my focus is on studying the impact of dysregulation of the transcription factor
TRβ, a member of the thyroid hormone receptor (TR) family in dedifferentiated thyroid tumors. The current
prognosis for patients with resistant or recurrent thyroid cancer is extremely poor. Due to the lack of effective
therapies, patients with advanced or metastatic thyroid cancer have a higher mortality rate than all other
endocrine cancers combined. Importantly, restoration of TRβ function in malignant cells decreases tumor growth
in xenograft studies. Despite a recognized role as a tumor suppressor, the mechanisms by which TRβ regulates
tumor growth are not clear. Therefore, I will address the critical need for a deeper understanding of thyroid
hormone receptor beta (TRβ) tumor suppressor mechanisms to inform the development more effective therapies
for aggressive thyroid cancer. The directly regulated genes of TRβ will be defined through an integrated analysis
of genome-wide binding and global gene expression data in thyroid cells. I will also determine the role that BRG1
plays in facilitating thyroid hormone induced chromatin remodeling, and its importance for maintenance of a
normal transcriptional profile in thyroid cells. These data will provide us with key insights into thyroid cancer
growth and progression, and allow for new target pathways to be explored as therapeutic options.
In the K00 phase, I propose to pursue my broader interests in nuclear receptor mediated epigenetic programming
and crosstalk in cancer in an environment which will allow me to expand my expertise hormone-mediated gene
regulation and my technical skill set. I have identified a critical gap in our current understanding of the impact of
hormone signaling on epigenetic regulatory mechanisms and changes in chromatin in structure. I plan to build
upon my current training to develop a project that addresses the epigenetic mechanisms by which hormone
signaling affects cancer cell identity, and translate these findings into clinically meaningful signatures. This work
will add depth to our current understanding of nuclear receptor biology, and advance our ability to effectively
treat hormone-dependent cancers with therapies that target nuclear receptors.

## Key facts

- **NIH application ID:** 10016237
- **Project number:** 5F99CA245796-02
- **Recipient organization:** UNIVERSITY OF VERMONT & ST AGRIC COLLEGE
- **Principal Investigator:** Noelle Elizabeth Gillis
- **Activity code:** F99 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $29,892
- **Award type:** 5
- **Project period:** 2019-09-11 → 2021-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10016237

## Citation

> US National Institutes of Health, RePORTER application 10016237, Nuclear Receptor Regulation of Epigenetics in Endocrine-Related Cancers (5F99CA245796-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10016237. Licensed CC0.

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