The Role of SPTSSB in the Synthesis of Long Chain Ceramides and Its Effect on Skin Barrier

Session Number

1

Advisor(s)

Amy Paller M.S. MD, Nihal Kaplan Ph.D., Northwestern University, Feinberg School of Medicine

Location

B115

Discipline

Biology

Start Date

15-4-2026 10:15 AM

End Date

15-4-2026 11:00 AM

Abstract

Atopic dermatitis (AD) is a chronic inflammatory skin disease associated with impaired barrier function and altered ceramide composition in the stratum corneum. Disruption of long-chain ceramide synthesis contributes to defective lipid organization and abnormal keratinocyte differentiation. We investigated the role of serine palmitoyltransferase small subunit B 51 (SPTSSB), a regulatory component of the rate-limiting enzyme complex in de novo ceramide synthesis, in epidermal development and barrier integrity. Three-dimensional human skin organoids were generated from primary keratinocytes and cultured at an air–liquid interface to promote stratification. SPTSSB expression was silenced using different lentiviruses, and RNA was analyzed to measure expression of SPTSSB and late differentiation markers, including filaggrin (FLG), and loricrin (LOR). Structural changes were assessed through immunofluorescence staining and fluorescence microscopy. We hypothesized that SPTSSB knockdown would reduce differentiation marker expression and disrupt epidermal organization, indicating compromised barrier formation. These findings aim to clarify the regulatory role of SPTSSB in ceramide biosynthesis and keratinocyte differentiation, supporting its potential as an early therapeutic target to restore lipid homeostasis in AD rather than solely addressing downstream inflammation.

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Apr 15th, 10:15 AM Apr 15th, 11:00 AM

The Role of SPTSSB in the Synthesis of Long Chain Ceramides and Its Effect on Skin Barrier

B115

Atopic dermatitis (AD) is a chronic inflammatory skin disease associated with impaired barrier function and altered ceramide composition in the stratum corneum. Disruption of long-chain ceramide synthesis contributes to defective lipid organization and abnormal keratinocyte differentiation. We investigated the role of serine palmitoyltransferase small subunit B 51 (SPTSSB), a regulatory component of the rate-limiting enzyme complex in de novo ceramide synthesis, in epidermal development and barrier integrity. Three-dimensional human skin organoids were generated from primary keratinocytes and cultured at an air–liquid interface to promote stratification. SPTSSB expression was silenced using different lentiviruses, and RNA was analyzed to measure expression of SPTSSB and late differentiation markers, including filaggrin (FLG), and loricrin (LOR). Structural changes were assessed through immunofluorescence staining and fluorescence microscopy. We hypothesized that SPTSSB knockdown would reduce differentiation marker expression and disrupt epidermal organization, indicating compromised barrier formation. These findings aim to clarify the regulatory role of SPTSSB in ceramide biosynthesis and keratinocyte differentiation, supporting its potential as an early therapeutic target to restore lipid homeostasis in AD rather than solely addressing downstream inflammation.