# TRANSCRIPTOME AND EPIGENOME MAPPING IN DOPAMINE NEURONS FROM THE OPIOID EXPOSED HUMAN BRAIN

> **NIH NIH R01** · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · 2021 · $659,280

## Abstract

Although many cells and neural circuits clearly contribute to opiate and other substance abuse disorder, the
path to drug addiction travels through midbrain dopaminergic neurons. Though a rare cell type (it is estimated
that a mere 1 of every 200,000 neurons in the human brain is of a dopaminergic phenotype), changes in
dopaminergic neurotransmission are thought to play a role in various stages of addiction, from acute reward
mechanisms and goal-directed actions, to the development of habitual behavior and increased salience of
cues associated with drug use, as well as the anhedonia and dysphoria associated with drug withdrawal.
Surprisingly little is actually known about persistent changes in gene expression that presumably underlie the
dysfunction of dopamine systems in brain exposed to opiates and other drug of abuse.
Our project is centered on three Specific Aims. In Aim #1,we will extract chromatin from immunotagged
midbrain dopaminergic neuron nuclei collected by fluorescence-activated sorting from 150 controls and 150
cases diagnosed with opiate abuse and then profile, on a genome-wide scale, the transcriptome and open
chromatin landscapes and promoter-enhancer loopings and other types of chromosomal conformations (the
‘3D genome’) in cell type-specific manner. In Aim #2, we will apply integrative genomics approaches and
leverage Aim #1 postmortem brain data with population-scale genotypes and phenotypes provided by the
Million Veterans Project and the Psychiatric Genomics Consortium to build causal probabilistic networks and
predict key drivers within the regulatory non-coding DNA space of the dopaminergic system. In Aim #3, we will
validate addiction-relevant cis-regulatory sequences (from Aim #1, #2) with small RNA-guided epigenomic
editing systems in cultured human dopaminergic neurons. Collectively, our midbrain dopaminergic neuron-
focused project will fill critical voids in the field of human addiction research and human neurogenomics and
embark, for the first time, on a deep epigenomic assessment of one of the key cell populations in reward and
addiction circuitry.

## Key facts

- **NIH application ID:** 10203901
- **Project number:** 5R01DA047880-03
- **Recipient organization:** ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
- **Principal Investigator:** Schahram Akbarian
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $659,280
- **Award type:** 5
- **Project period:** 2019-09-15 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10203901

## Citation

> US National Institutes of Health, RePORTER application 10203901, TRANSCRIPTOME AND EPIGENOME MAPPING IN DOPAMINE NEURONS FROM THE OPIOID EXPOSED HUMAN BRAIN (5R01DA047880-03). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10203901. Licensed CC0.

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