# Ganglioside interactome toolkit

> **NIH NIH U01** · JOHNS HOPKINS UNIVERSITY · 2021 · $495,977

## Abstract

Gangliosides, sialylated glycosphingolipids found on all vertebrate cells and tissues, play well-established
roles in diverse molecular signaling pathways that impact human diseases including diabetes, cancer, neuro-
degenerative proteinopathies, intellectual disability, and many others. The major ganglioside structures are
well-defined, finite, and shared across vertebrate species. Their glycans regulate cell signaling independent
of a protein carrier. Most gangliosides reside on the cell surface with their ceramide lipids embedded in the
plasma membrane and their glycans extending outward. They regulate cell physiology in two modes, cis and
trans. As cis regulators, they associate laterally via glycan binding to transmembrane proteins in the same
cell membrane to regulate their function. As trans recognition molecules they engage proteins in the
extracellular milieu or on apposing cells, mediating cell-cell interactions. Both cis and trans interactions are
specific for ganglioside glycan structures and essential for human health.
 Most ganglioside functions and ganglioside-protein interactions remain poorly understood due to lack of
broadly accessible, adaptable and validated tools and optimized methods for their use. It is the goal of this
project to address this need using chemical biology technologies to synthesize a defined set of major
gangliosides carrying minimally disruptive bifunctional photoreactive and alkyne (click chemistry) tags.
Optimized and validated protocols will be generated to deliver bifunctionally tagged gangliosides to the outer
leaflet of the plasma membrane of cells, where most gangliosides reside and function. Our goal is to
synthesize the ganglioside probe toolkit, validate appropriate cell delivery of the probes, validate their use to
identify glycan-specific ganglioside binding proteins, and transfer the reagents and protocols to other
biomedical research laboratories within the term of this project. The deliverables, ganglioside probes and
validated methods for their use, will be distributed broadly to biomedical researchers to discover the identities,
specificities, distributions and functions of ganglioside binding proteins relevant to a variety of human cells,
tissues, and diseases.

## Key facts

- **NIH application ID:** 10163818
- **Project number:** 5U01CA241953-03
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** RONALD L SCHNAAR
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $495,977
- **Award type:** 5
- **Project period:** 2019-07-01 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10163818

## Citation

> US National Institutes of Health, RePORTER application 10163818, Ganglioside interactome toolkit (5U01CA241953-03). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10163818. Licensed CC0.

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