# LITAF regulation of membrane repair and inflammation

> **NIH NIH R01** · BENAROYA RESEARCH INST AT VIRGINIA MASON · 2024 · $835,708

## Abstract

Project Summary
Membrane damage by mechanical or biochemical stress, leads to cell death and activation of innate immune
inflammatory pathways, and contributes to the pathology of many inflammatory conditions. Furthermore,
pathogens can secrete pore-forming toxins (PFT) to promote infection and disrupt immunity, and endogenous
pore-forming proteins such as Gasdermin D and MLKL have been shown to contribute to inflammatory signaling
and secretion of cytokines. Cells have evolved multiple mechanisms to repair membrane damage and maintain
cellular homeostasis, but our understanding of how damage is sensed and linked to repair remains incomplete.
We have recently developed a transposon-based forward genetic screening approach, which we have used to
identify genes that promote resistance to cell death induced by S. aureus α-toxin. We identified the lysosomal
membrane protein LITAF as a cell-autonomous inhibitor of cell death. In preliminary data, we show that LITAF
promotes sequestration of damaged membranes into vesicles through the activation of the ESCRT machinery.
We hypothesize that LITAF acts as an effector of cellular defense against pore-forming proteins, linking sensing
of membrane damage to effector mechanisms of repair. In this application, we propose to test this hypothesis
by: (1) identifying the mechanisms of LITAF activation and function; (2) determining the role of this pathway in
lung inflammation and infection; (3) testing whether LITAF regulates innate immune signaling, inflammasome
activation and inflammatory cell death in macrophages. This research is of high significance as it will provide a
deeper understanding of cellular defense mechanisms against membrane damage, and of the balance between
cell survival and inflammatory cell death. Identifying strategies to counteract membrane damage and prevent
cell death will contribute to understanding and treating the pathology of a wide range of infectious and
inflammatory diseases.

## Key facts

- **NIH application ID:** 10990964
- **Project number:** 1R01AI177971-01A1
- **Recipient organization:** BENAROYA RESEARCH INST AT VIRGINIA MASON
- **Principal Investigator:** Adam Lacy-Hulbert
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $835,708
- **Award type:** 1
- **Project period:** 2024-07-01 → 2029-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10990964

## Citation

> US National Institutes of Health, RePORTER application 10990964, LITAF regulation of membrane repair and inflammation (1R01AI177971-01A1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10990964. Licensed CC0.

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