# Elucidating single cell changes in neurogenic brain regions during HIV and cannabinoid exposure

> **NIH NIH U01** · WEILL MEDICAL COLL OF CORNELL UNIV · 2024 · $2,276,913

## Abstract

PROJECT SUMMARY (ABSTRACT)
The use of cannabis for recreation and medicinal purposes is disproportionately high among people living with
HIV (PLWH) and nearly half of cannabis using PLWH are estimated to be at risk for cannabis use disorder. Yet,
whether cannabis is therapeutic or detrimental on the central nervous system (CNS) of PLWH remains
controversial, highlighting the need for well-controlled studies generating reproducible data from specific
cannabinoids, brain regions, and CNS cell types. Our research has shown that cell-type specific epigenetic
patterns relate to HIV-associated cognitive impairment in PLWH, more frequent or recent cannabis use may
reduce myeloid inflammation and impact brain structure in PLWH, and our recent single cell studies of the CNS
in PLWH revealed distinct CSF microglia-like cells expressing CD204 in PLWH and ongoing HIV viral
transcription in cerebrospinal fluid cells despite ART. Prior research has shown neurogenic brain regions
including the subventricular zone of the lateral ventricles and hippocampus are of high relevance to persistent
HIV infection and cannabinoid exposures. However, critical gaps in understanding neurogenic brain regions at
single cell level in the setting of HIV and cannabinoid exposures remain. We are leveraging brain tissues from
an established oral dosing model of cannabidiol and THC in a nonhuman primate (NHP) model of HIV,
application of new single cell technologies permitting the simultaneous profiling of gene expression and open
chromatin from the same cell (10X Genomics Multiome: RNA+ATAC) in brain tissues, a new single cell assay
capable of measuring multiple histone modifications, and pharmacological profiling of current ART regimens and
cannabinoid levels in brain tissues. Our central hypothesis is a therapeutic role of cannabinoids in ameliorating
HIV neuropathogenesis in the CNS by enhancing the proliferation and survival of neural progenitor cells and
immature neurons and reducing glial inflammation. To identify cell types, epigenetic cell states, and gene
pathways relevant to neuropathogenesis, viral persistence, and cannabinoid exposures, we are harnessing 180
brain tissue samples from an established oral administration of either cannabidiol (CBD) or Δ9-
tetrahydrocannabinol (THC) in NHP and single cell assays (10X Genomics single nucleus multiome and a new
single cell assay developed at the NYGC capable of measuring the genome-wide presence of multiple histone
modifications and protein-DNA binding sites). Moreover, accompanying single cell data will be generated from
conserved neurogenic brain regions of human postmortem brain tissues from 40 donors based on HIV status
(+/-) and cannabis exposure (+/-). We will also explore the frequency of single cells in neurogenic regions of the
brain that are infected and impacted by cannabinoids by harnessing a bioinformatics pipeline that detects both
viral transcripts and transposase accessible provirus. This project will generate...

## Key facts

- **NIH application ID:** 10840398
- **Project number:** 5U01DA058527-02
- **Recipient organization:** WEILL MEDICAL COLL OF CORNELL UNIV
- **Principal Investigator:** Michael Jay Corley
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $2,276,913
- **Award type:** 5
- **Project period:** 2023-05-15 → 2028-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10840398

## Citation

> US National Institutes of Health, RePORTER application 10840398, Elucidating single cell changes in neurogenic brain regions during HIV and cannabinoid exposure (5U01DA058527-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10840398. Licensed CC0.

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