# Myeloid cell signaling pathways in neuroHIV

> **NIH NIH R21** · RUSH UNIVERSITY MEDICAL CENTER · 2022 · $237,000

## Abstract

Project Summary
Macrophages are central players in HIV-Associated Neurocognitive Disorders (HAND),
where they are implicated in neuroinflammation, neurotoxicity, and at times in
neuroprotection. Brain macrophages and microglia are sensitive to signals to micro-
environmental signals and display a wide range of activation states resulting in their
different functional roles. A critical barrier to harnessing macrophages for therapeutic
benefit lies in our limited understanding of the signals that regulate their phenotype and
function. We identified a unique subset of monocyte derived macrophages (MDMs)
regulated by Wnt7A. Wnt7A is a secreted glycoprotein expressed by neurons and
endothelial cells of the blood brain barrier, with central roles in BBB development,
neurogenesis, and synaptogenesis, to a name a few. We reported that Wnt7A-MDMs
are distinct from M-1 and M-2 like MDMs and exhibit an intermediate phenotype and
functional capacity. We hypothesize that macrophages differentiated under the
influence of Wnt7A are neuroprotective and will decrease CNS viral load. Using in
vitro, humanized mice, and brain post-mortem clinical studies we will define the impact
of Wnt7A-MDMs on HIV-associated neuropathogenesis (Aim 1) and determine the
association between Wnt7A levels in the CNS and the pathologic and clinical
manifestation of HIV (Aim 2). Together, these studies will define a unique pathway
driving macrophage phenotype and function and its impact on HIV-mediated
dysregulation in the CNS. This understanding can potentially be harnessed for cellular
therapeutic neuroprotection in context of HIV and/or other neurodegenerative diseases.

## Key facts

- **NIH application ID:** 10484541
- **Project number:** 1R21MH130266-01
- **Recipient organization:** RUSH UNIVERSITY MEDICAL CENTER
- **Principal Investigator:** Jennillee Wallace
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $237,000
- **Award type:** 1
- **Project period:** 2022-09-09 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10484541

## Citation

> US National Institutes of Health, RePORTER application 10484541, Myeloid cell signaling pathways in neuroHIV (1R21MH130266-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10484541. Licensed CC0.

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