# "Developing A Comprehensive Toolkit for Chemical Inducible Epigenome Remodeling"

> **NIH NIH R01** · CASE WESTERN RESERVE UNIVERSITY · 2022 · $322,000

## Abstract

Project Summary/ Abstract
 Distinct epigenetic mechanisms, including histone modifications, DNA methylation, chromatin remodeling
and histone variant exchange, collaboratively and dynamically shape local epigenetic landscape and control
gene activities. Alteration of epigenetic pathways and mutations in epigenetic regulators contribute to the
pathogenesis of various human diseases. Several studies suggest that these epigenetic pathways are
orchestrated to regulate activity-gene expression. Current tools to simultaneously manipulate multiple epigenetic
pathways in temporal and locus specific are lacking. Such tools are necessary to precisely dissect the functional
interplays and crosstalk between these distinct epigenetic mechanisms for gene regulation. To address this
limitation, we propose to establish unique chemical inducible methods that integrate dCas9/gRNA-guided
targeting with the orthogonal chemically induced proximity (CIP) technology to simultaneously control different
epigenetic regulations including all major epigenetic pathways. We will focus on the following three aims: (i)
Develop inducible dual editing platforms for diverse histone modifications; (ii) Develop chemical inducible
platforms for chromatin remodeling and nucleosome editing; (iii) Develop chemical inducible editing platforms
for DNA methylation and validate the orthogonal manipulation of multiple mechanisms across distinct epigenetic
pathways. After finishing this work, we expect to establish a unique toolset that can be readily used by
researchers in the field. This platform can be easily adapted and expanded to manipulate new epigenetic factors
not tested in this study. This new epigenome editing/remodeling platform will facilitate the advancement of
epigenetic research and potentially offer new directions in developing new epigenetic-based therapies.

## Key facts

- **NIH application ID:** 10440147
- **Project number:** 1R01GM143256-01A1
- **Recipient organization:** CASE WESTERN RESERVE UNIVERSITY
- **Principal Investigator:** Fu-Sen Liang
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $322,000
- **Award type:** 1
- **Project period:** 2022-07-01 → 2026-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10440147

## Citation

> US National Institutes of Health, RePORTER application 10440147, "Developing A Comprehensive Toolkit for Chemical Inducible Epigenome Remodeling" (1R01GM143256-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10440147. Licensed CC0.

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