# The Role of Sting in Lysosomal Storage Disorder

> **NIH NIH R21** · UT SOUTHWESTERN MEDICAL CENTER · 2024 · $238,468

## Abstract

PROJECT SUMMARY
Lysosomal storage disorder (LSD) is a collection of over 70 monogenic diseases associated with genetic
mutations in lysosomal enzymes or proteins. The clinical manifestations of LSD are heterogenous but often
include early-onset neurodegeneration with varying degrees of inflammation. The mechanism of inflammation
associated with LSD is unknown. We recently showed in Niemann-Pick disease type C1 that an intracellular
innate immune signaling pathway, STING, is activated due to impaired lysosomal degradation, leading to
inflammation and neuropathology. In this R21 application, we aim to directly examine whether STING is
required for pathogenesis of several lysosomal storage disorders using mouse models. We hypothesize that
STING is an “immunosensor” of lysosome activity and that lysosomal dysfunction activates the STING-
mediated immune signaling and lysosomal biogenesis. In Aim 1, we will breed mouse models of lysosomal
storage disorder with Sting-/- mice or treat with a STING antagonist to determine whether STING is required for
inflammation and disease pathogenesis. In Aim 2, we will elucidate the mechanisms of STING activation and
STING-mediated lysosomal biogenesis. Together, we hope to define STING as a new drug target in lysosomal
diseases. This study will also establish a new clinical paradigm for considering STING antagonists as first-line
therapy for many lysosomal storage disorders.

## Key facts

- **NIH application ID:** 10951042
- **Project number:** 1R21AI185226-01
- **Recipient organization:** UT SOUTHWESTERN MEDICAL CENTER
- **Principal Investigator:** Nan Yan
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $238,468
- **Award type:** 1
- **Project period:** 2024-06-06 → 2026-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10951042

## Citation

> US National Institutes of Health, RePORTER application 10951042, The Role of Sting in Lysosomal Storage Disorder (1R21AI185226-01). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10951042. Licensed CC0.

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