# Glycolipids of Neural Stem Cells

> **NIH NIH R01** · AUGUSTA UNIVERSITY · 2021 · $332,500

## Abstract

Gangliosides are glycosylated sphingolipids with essential but enigmatic function in brain development
and neural stem cell (NSC) maintenance. A critical barrier to our knowledge on ganglioside function in the
brain is the absence of a systematic approach targeting key regulatory mechanisms in NSC differentiation
instructed by gangliosides. Our group has pioneered research on the importance of gangliosides for growth
factor receptor signaling and epigenetic regulation of NSCs. The overall goal of this project is to further
elucidate the functional roles of gangliosides in NSCs based on contemporary concepts and technologies. The
primary localization of glycosphingolipids (GSLs) on cell-surface microdomains and the drastic dose and
composition changes during neural differentiation strongly suggest that GSLs are not only important as
biomarkers but also are involved in modulating NSC functions. Many stage-specific GSL antigens in NSCs are
now known, but less is understood about the mechanisms for their biological functions in modulating NSC cell
fate determination. Here we will perform cellular and molecular biological analyses to elucidate the expression
patterns of gangliosides, the functional roles of gangliosides in growth factor activation, and the mechanisms in
regulating glycosyltransferases (GTs) during neural differentiation. The overall goal will be achieved by the
following three specific aims: 1) To determine the expression of gangliosides in NSCs and the functional roles
of specific gangliosides in relation to specific growth factors and their receptors for regulating NSC cell fate
determination, such as self-renewal, proliferation, differentiation, migration, and survival. This will be achieved
by investigation of stage-specific gangliosides in growth factor-mediated cellular events in normal and GT
knockout mice; 2) To determine the regulatory mechanisms of GT expression in NSCs that account for the
dramatic changes of ganglioside expression (“pathway switch”) during differentiation. In particular, we will
study the post-translational regulation of GT expression by a novel enzyme complex formation mechanism at
key metabolic branching points of their biosynthesis; and 3) To determine a novel epigenetic regulatory
mechanism of GT expression in neuronal differentiation, particularly during postnatal neurogenesis. We will
test the hypothesis that nuclear GM1 is associated with gene regulation in neuronal cells. Since GSL
expression profiles are associated not only with normal development but also with pathogenic mechanisms of
diseases, the proposed studies will significantly enhance the understanding of the functional role of GSLs in
neurogenesis and the molecular mechanisms underlying the differential expression of stage-specific GSLs.
This information will be extremely useful in providing novel strategies for disease treatment and neural
regeneration by NSCs.

## Key facts

- **NIH application ID:** 10062520
- **Project number:** 5R01NS100839-04
- **Recipient organization:** AUGUSTA UNIVERSITY
- **Principal Investigator:** Robert K. YU
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $332,500
- **Award type:** 5
- **Project period:** 2017-12-15 → 2022-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10062520

## Citation

> US National Institutes of Health, RePORTER application 10062520, Glycolipids of Neural Stem Cells (5R01NS100839-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10062520. Licensed CC0.

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