# Transcriptional Mechanisms of Drug Addiction

> **NIH NIH P01** · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · 2020 · $1,821,689

## Abstract

PROJECT SUMMARY/ABSTRACT– OVERALL PPG
 This new Program Project Grant (PPG) utilizes recent advances in transcriptional biology to fundamentally
increase our knowledge of the long-lasting abnormalities in brain that underlie stimulant and opiate addiction.
Our work focuses on several specific cell types in key addiction-related brain regions: nucleus accumbens,
dorsal striatum, and prefrontal cortex. The PPG is composed of four Projects and three Cores all at Mount
Sinai. The PIs are leaders in their fields who have an established history of effective collaboration and use their
complementary expertise and approaches to chart a multidisciplinary course in the proposed research. Project
1 (Eric Nestler) focuses on novel transcription factors induced in brain reward regions by self-administered
stimulants and opiates. Project 2 (Paul Kenny) mines the PPG’s complex datasets to understand the role
played by circular RNAs in addiction; these are a newly discovered class of non-coding RNAs some of which,
within brain, are concentrated at synapses. Project 3 (Anne Schaefer) focuses on the influence of microglia in
controlling transcriptional responses to drugs of abuse within brain reward neurons and their behavioral
consequences. Project 4 (Yasmin Hurd) concentrates on the influence of enhancer regions, and their
transcriptional and chromatin mediators, in controlling molecular and behavioral adaptations to drugs of abuse.
All four projects validate findings from animals in human postmortem brain tissue, while discoveries in human
substance use disorders are fed back to animal models to explicate the underlying mechanisms involved. The
PPG is supported by three Cores, an Administrative Core (Eric Nestler) to oversee and coordinate PPG
operations; an Animal Models Core (Vanna Zachariou) to provide animal models of addiction and other
advanced tools (e.g., viral gene transfer, inducible mutant mice) to manipulate individual genes of interest in
specific cell types of the targeted brain regions and thereby provide causal evidence linking molecular-cellular
plasticity to addiction-related phenomena; and a Gene and Chromatin Analysis Core (Li Shen) to provide state-
of-the-art methods and bioinformatics to characterize genome-wide regulation of gene expression and
chromatin modifications in addiction. This pioneering investigation of transcriptional mechanisms of drug
addiction will help drive major advances in the field.

## Key facts

- **NIH application ID:** 9864063
- **Project number:** 5P01DA047233-02
- **Recipient organization:** ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
- **Principal Investigator:** ERIC J. NESTLER
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $1,821,689
- **Award type:** 5
- **Project period:** 2019-02-15 → 2023-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9864063

## Citation

> US National Institutes of Health, RePORTER application 9864063, Transcriptional Mechanisms of Drug Addiction (5P01DA047233-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9864063. Licensed CC0.

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