# Investigating the molecular mechanisms of HIV/AIDS associated neurological disorders using microglia and cerebral organoids derived from induced pluripotent stem cells

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2020 · $780,441

## Abstract

PROJECT SUMMARY
High prevalence of HIV-associated neurocognitive disorders (HAND) poses a major challenge
for the society. While there is evidence that both HIV-1 and methamphetamine can cause
behavioral, neurocognitive and histopathological changes in the brain, and affect immune
defense, the combined effect and potential interaction of both the virus and the drug remains
incompletely understood. In addition, fundamental and critical questions regarding how HIV-
infects microglia to establish latent infection and infected microglia alter neural tissue structure,
physiology, and function in brain remain to be addressed. The overall objective of this proposal
is to delineate the molecular and cellular mechanisms by which HIV infection alters the function
of microglia, resident immune cells of the brain, and CNS that leads to neuronal injury and
pathogenesis of HAND. Recent advances in embryonic stem cell and induced pluripotent stem
cells (iPSCs) technologies have opened up new avenues of disease modeling in vitro. We put
forward an unprecedented concept and experimental system to model human microglia-brain
interactions as well as opportunities to illuminate how genetic variation affects gene expression.
Our project has three specific aims: Specific Aim 1: Establish iPSC-derived cerebral organoids
and define the cellular diversity, neural tissue structure, physiology, and gene expression
programs. Specific Aim 2: Determine how HIV infection alters microglia and CNS during HIV
neuropathogenesis. Specific Aim 3: Determine the molecular mechanisms of neuronal injury by
HIV. Our results will be corroborated with gene expression programs using single nuclei of
microglia and neurons obtained from postmortem tissues of HAND patients. Gene targets of
HAND risk variants activity in disease-relevant cell types will be determined. Further, we will
validate our findings in human brain tissues through the National NeuroAIDS Tissue Consortium
(NNTC) and SIV infected brains of rhesus monkeys. Results of these studies will provide
fundamental understanding of the molecular mechanisms that are altered by HIV and
methamphetamine use leading to immune and brain dysfunctions.

## Key facts

- **NIH application ID:** 9971512
- **Project number:** 5R01DA049524-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** TARIQ M RANA
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $780,441
- **Award type:** 5
- **Project period:** 2019-09-01 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9971512

## Citation

> US National Institutes of Health, RePORTER application 9971512, Investigating the molecular mechanisms of HIV/AIDS associated neurological disorders using microglia and cerebral organoids derived from induced pluripotent stem cells (5R01DA049524-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9971512. Licensed CC0.

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