# Omics Analyses of HIV and Substance Use Disorder

> **NIH NIH R01** · SCRIPPS RESEARCH INSTITUTE, THE · 2021 · $856,189

## Abstract

Summary
 In order to generate new mechanistic hypotheses on neuroHIV pathogenesis and disease progression to
identify novel therapeutic targets to improve neuropsychological functioning in people with HIV, substance
abuse comorbidity and neurodegenerative diseases, this proposal will utilize convergent state-of-the-art Omics
strategies including transcriptomic, epitranscriptomic and proteomics. Specifically, we will carry out gene
expression profiles by RNA-Seq from the frontal cortex of HIV+ patients and controls representative of cART
era clinical presentations with and without histories of dependent substance abuse from samples of the
National NeuroAIDS Tissue Consortium (NNTC). We will bring to bear a systems biology framework to
generate mechanistic hypotheses that in preliminary studies allowed us to identify candidate drivers of gene
expression changes associated with neuroHIV and neurodegenerative diseases including Alzheimer’s and
Huntington’s diseases. The scientific literature together with our preliminary results, indicate that N6-
methyladenosine (m6A) RNA methylation represents an additional layer of host gene expression of great
potential pathogenic significance in both neuroHIV and Alzheimer’s disease. In particular, preliminary results
indicate that HIV induces altered m6A methylation of transcripts involved in pathways related to
synaptodendritic injury and neurodegeneration, inflammation and RNA processing, thus m6A RNA methylation
profiling will also be carried out. Excessive production of the signaling molecule nitric oxide (NO) leads to
protein S-nitrosylation, a posttranslational modification associated with aging, neurodegenerative diseases,
including Alzheimer’s and Parkinson’s diseases, and neuroHIV. Our preliminary data show convergent results
from analyses of gene expression and S-nitrosoproteomics. Therefore, we will integrate the transcriptomics
with Mass Spectrometry (MS) proteomic analysis of the S-nitrosoproteome. In summary, these studies will
apply an integrated Omics approach including little understood and emerging aspects of host-HIV regulatory
interactions, such as RNA-methylation and protein nitrosylation in a systems biology framework to generate
mechanistic hypotheses that will be tested in the second part of the grant to identify novel therapeutic concepts
to improve neuropsychological functioning in people with HIV, substance abuse comorbidity and
neurodegenerative diseases.

## Key facts

- **NIH application ID:** 10213682
- **Project number:** 5R01DA048882-03
- **Recipient organization:** SCRIPPS RESEARCH INSTITUTE, THE
- **Principal Investigator:** Vez REPUNTE-CANONIGO
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $856,189
- **Award type:** 5
- **Project period:** 2019-09-30 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10213682

## Citation

> US National Institutes of Health, RePORTER application 10213682, Omics Analyses of HIV and Substance Use Disorder (5R01DA048882-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10213682. Licensed CC0.

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