Robert H. Rice
S.B. in Physics, Massachusetts Institute of Technology, Cambridge, MA, 1967
Ph.D. in Molecular Biology, University of California, Berkeley, 1972
Our current work has two overall directions. First, we wish to understand themolecular basis of keratinocyte differentiation, including the regulation ofspecific markers, the coordination of marker expression and the reprogrammingthat occurs in squamous metaplasia. To this end, we are investigating thetranscriptional regulation of two markers, involucrin and keratinocytetransglutaminase (1, 2). The latter enzyme, which is membrane bound (3), stabilizes the cross-linked envelope of mature epidermal cells by cross-linkinga variety of proteins including involucrin, a major substrate in culturedkeratinocytes (4, 5). Lack of functional transglutaminase results in adebilitating skin disease, lamellar ichthyosis, in which the lack of isopeptidecross-linking is evident in mature cells of epidermis and appendages (6). Thesecond direction of our work involves studying the mechanisms by which toxicagents perturb keratinocyte function. Carcinogens and tumor promoters such asarsenic and dioxin (TCDD) have remarkable effects on epidermal differentiation(7-11). Elucidating the mechanisms by which these agents act is important forassessing the risk of exposure to such toxins in our environment, but will alsohelp understand keratinocyte programming. Most of the work in the lab employshuman keratinocytes derived from normal epidermis or squamous cell carcinomas,which in some cases show striking differences in properties such astranscription factor localization (12). In addition, a spontaneouslyimmortalized epidermal line has proven useful for studying the consequences ofelevation of endogenous telomerase activity (13, 14). Epithelial cells from avariety of rat tissues, exhibiting a keratinocyte phenotype in culture (15, 16),permit studies of species differences in biotransformation and toxic response(17, 18). Evolution of keratinocyte differentiation markers is also of interest(19, 20).