Reversal of tight junction dysfunction in atopic dermatitis by engaging EPHA2 signaling

Project: Research project

Project Details


Atopic dermatitis (AD) is a chronic, inflammatory skin disorder affecting up to 20% of children and adults globally and can adversely impact quality of life. The pathogenesis of AD is driven by abnormal immune responses and disturbances in epithelial barrier function. In skin, epidermal barrier function results from the cooperation of the lipid barrier and tight junction network. Recent evidence suggests a pivotal role of EPHA2 receptor tyrosine kinase in maintaining epidermal barriers. As such, we hypothesize that EPHA2 is a positive regulator of tight junctions and can be targeted to improve barrier function. We aim to test this hypothesis by asking if EPHA2 activation by ligand improves tight junction function in 3D models of AD. We will induce an AD-like phenotype by exposing 3D skin cultures to AD-relevant cytokines interleukin-4 and -13. We will test if ephrin-A ligand can prevent the tight junction dysfunction induced by these cytokines through analysis of trans-epithelial electrical resistance, protein and transcript levels of barrier genes, and immunofluorescence to visualize tight junction structure. This work will be performed in the Perez White laboratory located on the Northwestern University-Chicago campus. The Perez White laboratory is supported by an NIH-NIAMS K01 and institutional start-up funds.
Effective start/end date6/1/217/23/21


  • Dermatology Foundation (Agmt 04/05/21)


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