# Uncovering HIV/opioid effects in the brain at the single cell level: transcription, chromatin accessibility, and reservoir analysis in the SIV/cART/morphine/rhesus monkey model

> **NIH NIH U01** · UNIVERSITY OF NEBRASKA MEDICAL CENTER · 2024 · $1,579,167

## Abstract

Project Summary
A comprehensive interdisciplinary approach proposed to support the Single Cell Opioid Responses in the
Context of HIV (SCORCH) Program Expansion: CNS Data Generation for Chronic Opioid, Methamphetamine,
and/or Cocaine Exposures RFA from the National Institute on Drug Abuse (NIDA). We will perform studies on
the interplay of HIV pathogenesis and opioid abuse in the gold-standard SIV/nonhuman primate system, using
single-cell RNA sequencing (scRNAseq) to assess individual cellular transcriptomes. This will give us obtain
unparalleled insight into the viral and drug-induced effects on diverse cell types in brain in regions critical for HIV
infection and opioid abuse. In addition, we will also focus on primary targets of HIV and drivers of
neuropathogenesis, microglia and brain macrophages, using scRNAseq as well as single-cell Assay for
Transposase-Accessible Chromatin sequencing (scATACseq) to gain insight into the epigenetic regulation of
gene expression at the single cell level. These will be combined with state-of-the-art sensitive assays for virus
in the brain. We will ensure our data adhere to the FAIR (Findable, Accessible, Interoperable, and Reusable)
standards, and will work closely with other members of the SCORCH program to share and disseminate data to
yield maximal advancement to the field. Our experiments are carefully designed to address the role of virus,
drugs, and their interactions, as well as include the clinically relevant scenarios of those taking antiretrovirals to
suppress virus, and those who do not. Our rigor and reproducibility are facilitated by our detailed power analysis
with proper sample sizes, as well as our experimental design to match the standards of blocking, replication and
randomization. The results from these studies will provide novel insights into the CNS effects of HIV and drug
abuse.

## Key facts

- **NIH application ID:** 10877982
- **Project number:** 5U01DA053624-04
- **Recipient organization:** UNIVERSITY OF NEBRASKA MEDICAL CENTER
- **Principal Investigator:** Shilpa J Buch
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $1,579,167
- **Award type:** 5
- **Project period:** 2021-08-15 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10877982

## Citation

> US National Institutes of Health, RePORTER application 10877982, Uncovering HIV/opioid effects in the brain at the single cell level: transcription, chromatin accessibility, and reservoir analysis in the SIV/cART/morphine/rhesus monkey model (5U01DA053624-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10877982. Licensed CC0.

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