# Defining the role of lncRNA Neat1 and the nuclear paraspeckle in regulating macrophage innate immune gene expresison

> **NIH AI F31** · VANDERBILT UNIVERSITY · 2026 · $50,114

## Abstract

PROJECT SUMMARY
To ensure a robust immune response to pathogens without risking immunopathology, the kinetics and
amplitude of inflammatory gene expression in macrophages need to be exquisitely well-controlled. To mount
balanced inflammatory responses, macrophages need to be able to coordinate the transcription and
processing of thousands of genes that are synthesized de novo following pathogen sensing. Yet, we have an
incomplete understanding of the molecular mechanisms employed by macrophages to properly regulate the
timing and amplitude of inflammatory gene expression. Key to organization and compartmentalization of the
nucleus are biomolecular condensates. Condensates, which include structures like the nucleolus, Cajal body,
and nuclear speckle, are known to concentrate functionally related nucleic acids and proteins. We have
become interested in one such biomolecular condensate called the nuclear paraspeckle, which forms on a long
lncRNA called Neat1. Studies of model cell types (e.g. HeLa and HEK293T) have shown that paraspeckles can
aggregate in response to a variety of cellular stresses (e.g. osmotic stress, hypoxia, sodium arsenite), but how
paraspeckle dynamics change in response to more physiological stresses—and how they may help regulate
the cell’s response to stress—is not well-understood. My project aims to define the role of the paraspeckle in
macrophage activation. Our lab recently discovered that macrophage paraspeckles are dynamically regulated
over an early time-course of macrophage activation via lipopolysaccharide (LPS). We also found that in
response to LPS treatment, Neat1 KO macrophages fail to properly express a large cohort of proinflammatory
cytokines, chemokines, and antimicrobial mediators and consequently, cannot control replication of Salmonella
enterica or vesicular stomatitis virus (VSV). I hypothesize that macrophage paraspeckles regulate innate
immune gene expression by dynamically sequestering and/or releasing nuclear proteins/RN

## Key facts

- **NIH application ID:** 11318623
- **Project number:** 1F31AI197784-01
- **Recipient organization:** VANDERBILT UNIVERSITY
- **Principal Investigator:** Kaitlyn Samantha Armijo
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** AI
- **Fiscal year:** 2026
- **Award amount:** $50,114
- **Award type:** 1
- **Project period:** 2026-05-01T00:00:00 → 2029-04-30T00:00:00

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11318623

## Citation

> US National Institutes of Health, RePORTER application 11318623, Defining the role of lncRNA Neat1 and the nuclear paraspeckle in regulating macrophage innate immune gene expresison (1F31AI197784-01). Retrieved via AI Analytics 2026-07-12 from https://api.ai-analytics.org/grant/nih/11318623. Licensed CC0.

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