# The Epigenome in Substance Abuse Disorders: Engineering New Tools to Dissect Function from Form

> **NIH NIH DP1** · NORTH CAROLINA STATE UNIVERSITY RALEIGH · 2020 · $456,000

## Abstract

Many studies have connected epigenomic changes to substance abuse disorders. However, there is a 
key barrier to our understanding of the epigenome’s mechanistic roles. While epigenomic 
modifications have been widely mapped and correlated with changes in gene expression and cellular 
phenotypes, correlation does not demonstrate function or causation. This barrier arises because 
widely used techniques to perturb the epigenome, including pharmacological inhibition and genetic 
knock-outs or overexpressions, suffer from  pleiotropic effects. Thus, it is unclear if epigenomic 
modifications drive, are a result of, or are simply associated with changes in gene states. Two 
important corollaries arise from this: 1) It is unclear whether and which epigenome modifications 
drive changes in gene expression, and 2) the temporal stability of epigenome modifications that 
would result in truly persistent “epigenetic” properties is unknown. The hypothesis of the proposed 
work is that the epigenome represents a powerful regulatory system layered on top of the genome, 
and by engineering new tools to interface with and control this system, we can  harness  its  
unique properties to understand and tackle substance abuse disorders. A guiding goal is to dissect 
the function of epigenome modifications from their form and demonstrate their specific relevance to 
substance abuse disorders. To achieve this, we will develop tools to sense and induce changes in 
the epigenome, and do so spatiotemporally in systems reflective of human genetics, epigenetics, and 
physiology.

## Key facts

- **NIH application ID:** 9998953
- **Project number:** 5DP1DA044359-04
- **Recipient organization:** NORTH CAROLINA STATE UNIVERSITY RALEIGH
- **Principal Investigator:** Albert Keung
- **Activity code:** DP1 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $456,000
- **Award type:** 5
- **Project period:** 2017-09-01 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9998953

## Citation

> US National Institutes of Health, RePORTER application 9998953, The Epigenome in Substance Abuse Disorders: Engineering New Tools to Dissect Function from Form (5DP1DA044359-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9998953. Licensed CC0.

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