# Single cell chromatin profiling to study epigenetic alterations of ovarian tumors

> **NIH NIH K99** · UNIV OF MASSACHUSETTS MED SCH WORCESTER · 2022 · $124,681

## Abstract

PROJECT SUMMARY
An understanding of how epigenetic changes rewire the regulatory network of cancer cells would facilitate the
development of new therapeutic strategies. However, tumor heterogeneity hinders the study of epigenetic
landscapes in cancer. I propose to leverage a new single-cell genome profiling technology I recently developed
to map epigenetic changes in single cells, allowing me to characterize different cell populations within ovarian
tumors, including cancer stem cells (CSCs) and more differentiated cell types. These studies will uncover how
the epigenome is re-wired upon inhibition of epigenetic enzymes implicated in multiple cancers. EZH2 is a
histone methyltransferase that is often overexpressed in different types of cancer, including ovarian cancer,
and inhibition of EZH2 has been shown to strongly reduce the aggressiveness of tumors by impairing
metastasis, reducing invasiveness, and promoting differentiation. Yet, how EZH2 overexpression alters the
repressive histone mark, H3K27me3 in each tumor cell type remains unknown. I propose three Aims, the first
of which will use a combination of single cell Multi-CUT&Tag—a single cell profiling technology I recently
developed—and scRNA-seq to characterize the epigenomic landscapes in each ovarian cancer cell type. In
Aim 2, I will examine how perturbation of EZH2 alters the epigenetic architecture of tumor sub-populations,
including CSCs, and identify how EZH2 promotes CSC self-renewal and tumor progression. Finally, in Aim 3, I
will uncover the roles of genes and pathways subjected to epigenomic remodeling, in order to identify potential
weaknesses that can be exploited therapeutically. Successful completion of these studies will provide
considerable insight into the epigenetic regulation of CSCs in ovarian cancers and candidates for new
therapies for ovarian cancer treatment. In addition, these studies will provide extensive training in tumor
biology and single cell bioinformatics, which will be essential for my goal of running an independent group
focused on tumor epigenetics.

## Key facts

- **NIH application ID:** 10506998
- **Project number:** 1K99CA273420-01
- **Recipient organization:** UNIV OF MASSACHUSETTS MED SCH WORCESTER
- **Principal Investigator:** Sneha Gopalan
- **Activity code:** K99 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $124,681
- **Award type:** 1
- **Project period:** 2022-09-01 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10506998

## Citation

> US National Institutes of Health, RePORTER application 10506998, Single cell chromatin profiling to study epigenetic alterations of ovarian tumors (1K99CA273420-01). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10506998. Licensed CC0.

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