# Characterizing the Physicochemical Properties of Estrogen Receptor-mediated Transcriptional Condensates in Breast Cancer

> **NIH NIH F31** · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · 2021 · $46,036

## Abstract

Project Summary/ Abstract
 The transcription apparatus undergoes liquid-liquid phase separation to form a
biomolecular condensate at super-enhancer (SE)-regulated genes. Biomolecular condensates
are currently being characterized throughout the cell, exchanging the traditional stoichiometric
models of several biochemical mechanisms for super-stoichiometric models in which
components of the condensate are concentrated and functionally compartmentalized into
membrane-less organelles.
 A transcriptional condensate model has several implications for the basic molecular
mechanisms of gene activation, as well as for our understanding of transcriptional dysregulation
in cancer and in vivo target engagement in cancer therapy. In this research, we examine these
implications through a study of the emergent physicochemical properties, driving interactions,
and small molecule partitioning of Estrogen Receptor-mediated transcriptional condensates in
breast cancer. Our preliminary data began to characterize these condensates in breast cancer
tissue, cell lines, and in vitro. To build on these findings, we propose to use live-cell imaging and
established condensate characterization assays to pursue the following aims:
 1) Dissect the physicochemical properties of the Estrogen Receptor and Mediator in
 transcriptional condensates
 2) Identify features important for the phase separation capacity of the Estrogen Receptor
 with Mediator
 3) Build and utilize tools to characterize the properties of tamoxifen that determine its
 differential partitioning
 The work in this study will provide tools and a framework with which to consider future work
on the impact of alterations to ER and/or MED1 on SE-mediated gene transcription in breast
cancer cells. More broadly, by performing a deep dive into a well-studied TF-coactivator pairing
in cancer, this work may inform analyses on lesser-studied cancers in which transcription is
dysregulated, and a condensate model may provide insight or a therapeutic window.
 The proposed research will be conducted under the mentorship of Dr. Richard A. Young
at the Whitehead Institute for Biomedical Research. The fellowship training plan will provide the
trainee with skills in independent research, experimental techniques, scientific communication,
leadership, and mentorship through one-on-one meetings with the sponsor, lab meetings, and
presentation opportunities in and beyond the Whitehead and MIT Biology community.

## Key facts

- **NIH application ID:** 10128183
- **Project number:** 5F31CA250171-02
- **Recipient organization:** MASSACHUSETTS INSTITUTE OF TECHNOLOGY
- **Principal Investigator:** Lena Afeyan
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $46,036
- **Award type:** 5
- **Project period:** 2020-04-01 → 2022-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10128183

## Citation

> US National Institutes of Health, RePORTER application 10128183, Characterizing the Physicochemical Properties of Estrogen Receptor-mediated Transcriptional Condensates in Breast Cancer (5F31CA250171-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10128183. Licensed CC0.

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