# Project 2. Investigating epigenetic circuitry in multiple myeloma

> **NIH NIH P01** · DANA-FARBER CANCER INST · 2021 · $265,217

## Abstract

Project Summary (Project 2)
The overarching goal of this project is to study key features of epigenetic circuitry in MM, with the objective of
improving our understanding of global gene regulation in this cancer, and with the goal of deploying novel
therapeutics that target key epigenomic circuits in MM as dependencies. Cells and cell states can be defined
by their gene expression programs, and tumor cells commonly have deregulated gene expression programs.
The production of a gene expression program is accomplished by the cell’s epigenetic apparatus. It is now
possible, for any normal or cancer cell type, to identify the master transcription factors, the enhancer elements
they occupy, and the genes they regulate, and thus to develop a testable model of this genome-wide
epigenetic circuitry. Furthermore, it is possible to identify the gene regulatory elements on which the cell is
most dependent, and thus identify the portions of the circuitry on which a cancer cell is most dependent.
Tumor cells tend to develop striking dependencies on super-enhancer regulatory elements (3-6). Recent
studies suggest that the transcriptional cofactors BRD4, CDK7 and CDK12 play especially important roles in
tumor cell epigenetic circuitry, and their inhibition with small molecules can cause a loss of super-enhancer
domains that drive genes with prominent roles in tumorigenesis (3-6). We propose to decipher the key features
of MM epigenetic circuitry, to identify the features that confer great dependency, and to investigate the
potential of small molecule inhibitors to disrupt those dependencies in MM. To accomplish these goals, the
specific aims of the proposal are 1) To discover key features of epigenomic circuitry in multiple myeloma by
integrated epigenomic analysis, 2) to determine epigenetic dependencies in multiple myeloma using gene
editing approaches, and 3) to explore the ability of small molecule inhibitors of transcriptional cofactors to
disrupt key nodes in multiple myeloma epigenetic circuitry.

## Key facts

- **NIH application ID:** 10226193
- **Project number:** 5P01CA155258-10
- **Recipient organization:** DANA-FARBER CANCER INST
- **Principal Investigator:** RICHARD YOUNG
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $265,217
- **Award type:** 5
- **Project period:** 2011-12-01 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10226193

## Citation

> US National Institutes of Health, RePORTER application 10226193, Project 2. Investigating epigenetic circuitry in multiple myeloma (5P01CA155258-10). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10226193. Licensed CC0.

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