Toxicology and Applied Pharmacology

Biography

Dr. Thomas Slaga has more than 45 years of experience in studying the mechanisms of carcinogenesis and chemoprevention and directing and establishing research centers. He is currently a Professor in the Department of Pharmacology, Associate Director for Basic Research of the NCI designated Cancer Center, Director of the Texas Consortium of Chronic Disease Prevention and Director of the Regional Health Science Center at Edinburg. Dr. Slaga started an active leadership role when he became head of an interactive research program on carcinogenesis and chemoprevention at the Oak Ridge National Laboratory. Later he became Director of the UTMDACC-SP whose mission was multidisciplinary and interactive research on cancer causation and prevention. Dr. Slaga became Scientific Director at the AMC Cancer Research Center and Deputy Director of the University of Colorado Comprehensive Cancer Center. Dr. Slaga has an important leadership role nationally and internationally in carcinogenesis and cancer prevention having started the Journal of Molecular Carcinogenesis. He has served on many review committees such as a full member and chair of the Chemical Pathology Study Section, American Cancer Society review groups, Cancer Center review groups and program project review committees. He also served on several NIEHS, EPA and FDA review committees. Dr. Slaga also serves on the Board of Directors for the Aspen Cancer Conference and several scientific advisory committees. He has a very active and funded research program. Continuously funded since 1974, his research program is currently supported by several R01 grants. He has over 300 peer reviewed publications and over 200 invited review articles, book chapters and scientific books on cancer as well as a lay book entitled, "The Detox Revolution" which emphasizes the importance of diet, nutrition and phytonutrients in chronic disease prevention.

Research Interest

The research in Dr. Thomas Slaga's laboratory is focused on glucocorticoid hormones (GC), very potent inhibitors of physiological DNA synthesis in keratinocytes in vivo. These hormones are also very effective in preventing carcinogen- and tumor promoter-induced skin hyperplasia, inflammation, and mouse skin tumor formation when applied to skin together with a carcinogen or a tumor promoter. We and others have shown, however, that the GC do not affect the growth of either established papillomas, squamous cell carcinomas (SCC), or transformed keratinocytes in vitro. In addition, we recently found that the GC do not affect glucocorticoid-responsive genes in transformed keratinocytes both in vitro and in vivo. We have generated skin-targeted transgenic mice over-expressing the GR under the control of the keratin 5 (K5) promoter. These adult transgenic mice have impaired proliferative and inflammatory responses to skin tumor promoters. Our initial studies showed that the K5.GR transgenic animals are resistant to ras-induced tumorigenesis. The constitutively nuclear overexpression and activation of the GR in the epidermis dramatically inhibited skin tumor development in K5.GR/ras+ double transgenic mice in terms of number of animals that develop tumors, number of tumors per animal, and tumor size. In another study we plan to determine the mechanism(s) of synergistic action of the natural source compounds, known to inhibit one or more stages of skin carcinogenesis, i.e., initiation and promotion/progression. The concurrent topical and systemic (i.e., dietary) treatment with selected natural source inhibitors of different stages of skin carcinogenesis result in synergistic effects leading to more efficient prevention of skin cancer. The natural source inhibitors to be tested include ellagic acid, imperatorin from the family of coumarins, proanthocyanidin B-2-gallate, (-)-epigallocatechin from the family of green tea polyphenols, N-acetylcysteine, calcium D-glucarate, lycopene, carnosol and ursolic acid from rosemary extract, and resveratrol. We propose to initially utilize a number of very predictive short-term in vitro and in vivo tests in order to identify the mechanism(s) and to differentiate the potencies of selected inhibitors at various concentrations under standard conditions. The most effective compounds will then be studied in long-term tumor experiments utilizing a 7,12-dimethylbenz[a]anthracene (DMBA)-induced 12-O-tetradecanoylphorbol-13-acetate (TPA)-promoted multistage carcinogenesis model in SENCAR mice.