# Sphingolipid Biosynthesis in the Healthy and Diseased Epidermal Barrier

> **NIH NIH R01** · VIRGINIA COMMONWEALTH UNIVERSITY · 2024 · $706,710

## Abstract

Abstract/Summary
The stratum corneum contains unique species of the sphingolipid ceramide and that unique constellation is
essential for formation of the epidermal permeability barrier and is altered in diseases such as atopic dermatitis.
These ceramides are composed of fatty acids linked to a set of sphingoid backbones. The species of sphingoid
backbones found in the epidermis are highly unique. The premise of this application is that the unique
sphingoid backbones found in the epidermis are essential for formation of a fully functioning
permeability barrier and that alterations to that composition contributes to compromised barrier function
in skin diseases. These concepts have not previously been experimentally addressed. The sphingoid
backbones are generated by the serine palmitoyltransferase (SPT) complex, a hetero-oligomeric enzyme
composed of four subunits. Three of these four subunits have alternate isoforms. Depending on which isoforms
are expressed, SPT generates distinct sphingoid backbones. Our preliminary data demonstrates that during
keratinocyte differentiation there is a dramatic increase in the SPT subunits expected to generate the unique
sphingoid bases of the epidermis. The ability to genetically alter the expression of the epidermal SPT subunits
provides an avenue to directly test the role of epidermal-specific sphingoid backbones in development of the
epidermal permeability barrier. We will utilize both organoid culture systems and the intact animal to test this
concept. Additionally, we will utilize an animal model of atopic dermatitis to examine the role of these SPT
subunits in the etiology of that disease. Through collaboration between experts in keratinocyte biology and skin
disorders (Dr. Paller and the Northwestern SBDRC) and lipidomics/the SPT complex (Drs. Wattenberg and
Cowart at Virginia Commonwealth), we will fill key gaps in understanding the epidermal lipid barrier through this
regulatory mechanism

## Key facts

- **NIH application ID:** 10981643
- **Project number:** 1R01AR083443-01A1
- **Recipient organization:** VIRGINIA COMMONWEALTH UNIVERSITY
- **Principal Investigator:** Lauren Ashley Cowart
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $706,710
- **Award type:** 1
- **Project period:** 2024-07-01 → 2029-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10981643

## Citation

> US National Institutes of Health, RePORTER application 10981643, Sphingolipid Biosynthesis in the Healthy and Diseased Epidermal Barrier (1R01AR083443-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10981643. Licensed CC0.

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