# Irving Estevez_Diversity Supplement: R01 NS120895

> **NIH NIH R01** · RUTGERS, THE STATE UNIV OF N.J. · 2022 · $83,816

## Abstract

Abstract
 Astrocytes are versatile glial cells that regulate diverse processes in the central nervous system (CNS).
Roles for astrocytes during disease are complex and include both protective and pathologic functions. Recently,
distinct astrocyte activation states have been described, though the molecular mechanisms that govern astrocyte
polarization during neurotropic viral infection are not well understood. Here, we propose that receptor-interacting
protein kinase-3 (RIPK3) is a previously unappreciated driver of inflammatory astrocyte activation during viral
infection of the CNS. While roles for RIPK3 in programmed cell death have been extensively characterized, our
published work has described pleiotropic, cell death-independent functions for this pathway in the coordination
of protective neuroinflammation during viral encephalitis. In preliminary studies, we now show that RIPK3
signaling in astrocytes is required for survival and virologic control following challenge with Zika virus, an
emerging neurotropic pathogen of global concern. Using a combination of novel mouse genetic tools, we will
elucidate roles for RIPK3 signaling in astrocytes by 1) Defining profiles of expression, activation, and antiviral
function for astrocytic RIPK3; 2) Determining roles for astrocytic RIPK3 signaling in coordinating
neuroinflammation; and 3) Defining key substrates and transcriptional outputs of RIPK3 signaling in astrocytes.
Together, our studies promise to identify new molecular mechanisms governing protective neuroimmune function
during viral encephalitis.

## Key facts

- **NIH application ID:** 10526465
- **Project number:** 3R01NS120895-02S2
- **Recipient organization:** RUTGERS, THE STATE UNIV OF N.J.
- **Principal Investigator:** Brian Daniels
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $83,816
- **Award type:** 3
- **Project period:** 2021-02-15 → 2025-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10526465

## Citation

> US National Institutes of Health, RePORTER application 10526465, Irving Estevez_Diversity Supplement: R01 NS120895 (3R01NS120895-02S2). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10526465. Licensed CC0.

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