Defense Date


Document Type


Degree Name

Master of Science



First Advisor

Brian Wattenberg


The epidermis, the outermost layer of the skin, serves as a vital barrier protecting the body from environmental stressors, pathogens, and dehydration. Keratinocytes, the predominant cell type in the epidermis, play a central role in maintaining skin integrity and barrier function. In normal human skin, keratinocytes move from the basal layer to the stratum corneum, the top layer of the epidermis. In their travel, keratinocytes undergo a process of terminal differentiation, loss their ability to proliferate, secrete sphingolipids into the extracellular space, and gradually loss their nucleus and organelles. Sphingolipids, particularly ceramides, are key components of the intercellular lipid lamellae and contribute to the formation of the skin barrier permeability. The biosynthesis of sphingolipids occurs within keratinocytes through intricate enzymatic pathways. Serine palmitoyl-transferase SPT is the first and rate-limiting enzyme in the de novo synthesis pathway of sphingolipids. SPT is regulated by ORMDL to maintain the balance of sphingolipids within cells. Perturbations in sphingolipid metabolism have been linked to skin disorders characterized by impaired barrier function, such as atopic dermatitis and psoriasis. In the skin, knocking out ORMDL could lead to increased SPT activity and altered levels of sphingolipids, including ceramides. Changes in ceramide composition may influence skin barrier function and improve its permeability. Understanding the role of ORMDL knockout in the skin could have implications for the development of therapeutic strategies. Modulation of sphingolipid metabolism or manipulation of ORMDL may be explored for managing skin conditions.


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