# Determining the Roles of Sphingolipids in Phagocytosis

> **NIH NIH R21** · OREGON HEALTH & SCIENCE UNIVERSITY · 2022 · $199,172

## Abstract

PROJECT SUMMARY
Phagocytosis is a conserved cellular process that is essential for innate immune responses, tissue
homeostasis and is associated with various pathologies, including microbial susceptibility and autoimmune
disorders. Although phagocytosis was first described more than a century ago, most of the molecular
mechanisms that govern the different stages of phagocytosis, especially the lipid-protein interaction events, are
poorly understood. Studies have shown that phagocytosis involves complex membrane reorganization that
requires extensive remodeling of lipids at the cell surface. However, the roles of lipids, such as sphingolipids
(SPLs) in phagocytosis, remain mostly unknown. We hypothesize that both structural and bioactive SPLs are
critical determinant factors in phagocytosis where they are involved in signaling at the phagocytic synapse
and/or help form the biophysical structure of the phagosome through recruiting proteins to the newly formed
phagosomes. We recently found that the biosynthesis of sphingomyelin (SM), one of the major SPLs in
mammalian cells, is critical for phagocytosis. Whether SM itself or its biosynthetic byproducts are essential for
this process is unknown. In this application, we plan to characterize the exact lipid species required for
phagocytosis. To this end, we will take chemical and genetic approaches to disrupt SM catabolism at multiple
points along its degradative pathway in order to examine the roles of distinct SM-derived lipid species during
phagocytosis. To gain insight into the mechanism by which these lipids play roles in this process, we also plan
to determine the localization, metabolic conversions, and interacting partners of SPLs during phagocytosis. For
this, we will employ the recently reported genetically encoded SM biosensor as well as our novel multi-
functional SPL precursor analogs. These tools will allow us to examine the subcellular localization of SPLs in a
time- and space-dependent manner. Our functional probes will enable us to identify SPL interacting proteins
during the different stages of phagocytosis. An understanding of how these class of lipids enables
phagocytosis will reveal insights into this fundamental cellular process and help develop therapeutic strategies
to pathologies related to phagocytic disorders.
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## Key facts

- **NIH application ID:** 10432109
- **Project number:** 5R21AI156174-02
- **Recipient organization:** OREGON HEALTH & SCIENCE UNIVERSITY
- **Principal Investigator:** Fikadu G. Tafesse
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $199,172
- **Award type:** 5
- **Project period:** 2021-06-16 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10432109

## Citation

> US National Institutes of Health, RePORTER application 10432109, Determining the Roles of Sphingolipids in Phagocytosis (5R21AI156174-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10432109. Licensed CC0.

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