Epithelial cell adhesion to the basal lamina and the formation of hemidesmosomes is critical to the health and integrity of the cornea. Hemidesmosomes are root-like structures along the basal surface and bridge the epithelium and stromal matrix. Hyperplasia and/or faulty adhesion of epithelium may be caused by various diseases or trauma such as chemical or thermal burns. The overall goal of this proposal is to determine how injury and the subsequent release of cellular factors induces changes in migration and the assembly and/or disassembly of hemidesmosomes. Specifically, the aims of the project are to 1) isolate and determine the hierarchy of injury-induced signal transduction mediated events in the corneal epithelium; 2) characterize the role of specific hemidesmosome proteins; and 3) define the role of growth factors on the integrity of hemidesmosomes and their transition to migratory structures. The adhesion and wound models developed by the applicant will be used to examine these interactions. To achieve these aims, the applicant will use live cell imaging of wounds and analyze the expression of adhesion receptors and hemidesmosome proteins at specific intervals. The responses will be correlated with changes in protein localization and hemidesmosome formation. A better understanding of the factors that control the normal wound repair process will provide important insight into the treatment of epithelial disorders.
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