The effects of sunlight on skin are initiated by photochemical reactions of endogenous light-absorbing molecules (chromophores). After light absorption, the chromophore reacts with cellular molecules or generates reactive species, such as free radicals, that subsequently alter cellular molecules. Signal transduction pathways transform the initial light-mediated events into cellular responses such as new gene expression, apoptosis, transformation and cell cycle modulation. We are interested in identifying mechanisms, both photochemical and cell biological, for effects of UV radiation on skin.
Photobiology of UV Radiation
One goal of our work is to devise methods to prevent or ameliorate chronic UV-induced damage to skin. Chronic exposure to solar UV radiation causes major changes in the dermis, the lower layer of skin even though UV radiation is absorbed largely in the upper layer, the epidermis. The dermal elastic fibers increase and become amorphous (solar elastosis). Our current work focuses on how UV-induced signals are transmitted from the epidermis to the dermis and on the synthesis and degradation of the major protein components of elastic fibers. These studies utilize transgenic, knockout and spontaneous mutant mice and skin equivalents.
Free Radicals
Our research also delves into the primary membrane-associated signaling events initiated by reactive oxygen species that lead to apoptosis and new gene expression. We have shown that alterations in specific plasma membrane functions are strongly influenced by the site within the plasma membrane where a reactive species is produced and by the identity of the reactive species, e.g., singlet oxygen versus free radicals. Our recent results indicate that singlet oxygen causes very rapid down regulation of EGFR signaling in normal human keratinocytes by degradation of EGFR by a caspase-3 mediated process and also dephosphorylation of EGFR. In contrast, hydrogen peroxide up regulated EGFR signaling. The results of these studies may be used to develop new approaches to phototherapies. |
