Defense Date
2026
Document Type
Thesis
Degree Name
Master of Science
Department
Biochemistry
First Advisor
Brian Wattenberg
Abstract
The epidermis, the outermost layer of the skin, serves as an important barrier protecting the body from environmental stress, pathogens, and dehydration. Keratinocytes, the major cell type of the epidermis, undergo a process of terminal differentiation as they migrate from the basal layer to the stratum corneum. During this process, keratinocytes lose their ability to proliferate and produce large amounts of sphingolipids that are essential for epidermal barrier formation. Ceramides are the major sphingolipids found in the skin and are critical components of the extracellular lipid matrix that maintains skin permeability and barrier integrity. Alterations in ceramide composition and sphingolipid metabolism have been associated with inflammatory skin disorders such as atopic dermatitis and psoriasis.
Serine palmitoyltransferase (SPT) is the first and rate-limiting enzyme in the de novo sphingolipid biosynthesis pathway and is negatively regulated by ORMDL proteins to maintain sphingolipid homeostasis. Although ORMDL regulation of SPT has been studied in other systems, its role in keratinocyte differentiation and epidermal biology remains poorly understood. N-TERT keratinocytes were differentiated under high calcium conditions to examine changes in expression of the SPT/ORMDL complex during differentiation. Quantitative real-time PCR and western blotting demonstrated altered expression of several SPT and ORMDL subunits as keratinocytes differentiated, suggesting remodeling of sphingolipid biosynthetic pathways during epidermal maturation. Together, these findings provide insight into the regulation of sphingolipid metabolism in keratinocytes and establish a foundation for future therapeutic approaches targeting skin barrier disorders.
Rights
© The Author
Is Part Of
VCU University Archives
Is Part Of
VCU Theses and Dissertations
Date of Submission
5-8-2026