# Quantifying gene expression and network regulation in single cells to reveal the consequences of stress on the immune response

> **NIH NIH F32** · UNIVERSITY OF CHICAGO · 2020 · $65,310

## Abstract

PROJECT SUMMARY
 Human health is profoundly affected by genetics and the environment. The social environment mediates
changes in physiology, gene regulation, and immune signaling, resulting in significant differences in disease
susceptibility and mortality. Chronic social stress and social inequity are major drivers of disease, in part due to
effects on the immune response to infectious pathogens. However, the molecular mechanisms underlying these
effects are poorly understood. In order to address this gap, robust experimental models for uncovering social
environmental effects on the immune system are needed.
 Rhesus macaques are primates closely related to humans. In social groups, they maintain stable
hierarchies of social dominance, and these hierarchies can be experimentally manipulated through social group
rearrangement. Thus, they provide a unique resource to study causal social rank effects on disease. Although
significant and substantial gene expression changes in peripheral blood have been found to be associated with
social rank, the cell types underlying these signatures are not well-characterized. Single-cell RNA-sequencing
enables the discovery of effects of the social environment on individual cells of many kinds, which can help with
the targeting of clinically-relevant cell types that are responsible for immune dysregulation. Therefore, this work
proposes to study rank effects on gene regulation in individual peripheral blood cells, at baseline and after
immune stimulation, to uncover cell-type-specific social stress effects on immunity.
 The basic research question driving this proposal is: How does the social environment affect gene
expression across diverse peripheral blood immune cells? To answer this question, the approach of this proposal
is to use a well-established model of social adversity in captive female rhesus macaques, and to apply next-
generation single-cell RNA-seq technology to deeply characterize cells isolated from 50 individuals across a
social gradient. From this data, effects of social rank will be examined for: (1) immune composition and LPS-
induced polarization, (2) gene expression robustness across cell types, and (3) gene regulatory networks and
co-expression modules. Through this work, clinically-relevant genes and pathways will be identified that are
rewired by social environment effects, in order to design targeted therapeutics to improve immune responses
relevant to cancer and infectious disease.

## Key facts

- **NIH application ID:** 9992464
- **Project number:** 1F32AG064883-01A1
- **Recipient organization:** UNIVERSITY OF CHICAGO
- **Principal Investigator:** Paul L Maurizio
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $65,310
- **Award type:** 1
- **Project period:** 2020-06-01 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9992464

## Citation

> US National Institutes of Health, RePORTER application 9992464, Quantifying gene expression and network regulation in single cells to reveal the consequences of stress on the immune response (1F32AG064883-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9992464. Licensed CC0.

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