Epidermolysis bullosa simplex, EBS, is an inherited blistering disease caused by mutations in either K5 or K14 keratin genes. We hypothesized that increasing the levels of K15, a keratin similar to K14, may be beneficial for those EBS patients who have a disruptive mutation in K14. In our previous, preliminary studies, we cast a wide net to identify potential ways to increase K15 production. We found that thyroid hormone and interferon, an anti-viral protein, potently and specifically increase K15 production. The specificity is important, because agents that increase K15 and K14 simultaneously would not be as effective; interferon and thyroid hormone do not increase K14 production.

In follow-up studies, we comprehensively determined the effects of interferon in epidermal cells, keratinocytes. We found that interferon, besides boosting K15, inhibits proliferation of these cells as well as their differentiation, the process that creates the impermeable dead layer on the surface of skin. Inhibition of proliferation and differentiation may cause unacceptable side effects of interferon therapy, especially in the long term.

In this project, we propose to determine comprehensively the effects of thyroid hormone in epidermal cells. We expect that the side effects of thyroid hormone treatment will be milder than of interferon because skin symptoms in patient with thyroid diseases are relatively mild. Therefore, we propose to use a novel genomic methodology, microarray analysis, "DNA chips", to analyze thyroid hormone-treated epidermal cells in culture, as well as in human skin samples that would ordinarily be discarded during surgery. The results may confirm the safety, or indicate possible side effects of topical thyroid hormone treatment before treatments of human subjects begin.