Elaine L. Jacobson
Professor of Pharmacology & Toxicology; Ph.D., Kansas State University, 1971
elaine.jacobson@pharmacy.arizona.edu

Optimizing Molecular and Cellular Responses to UV Radiation in Skin; Inhibition of Advanced Glycation End-Products; DNA Damage and Repair

Research Activities

My research group is working to understand molecular and cellular responses to genotoxic stresses, particularly UV radiation and to translate that information to clinical applications in the prevention of skin cancer.  We are interested in optimizing skin cell nutrients by topical delivery systems that promote DNA repair and optimize energy status and in identifying prodrugs that prevent skin cell damage and skin cancer.  One of the consequences of DNA damage repair is poly(ADP-ribose) polymerase (PARP)-catalyzed destruction of the active form of niacin, NAD, and the generation of free ADP-ribose in chromatin.  ADP-ribose is a potent glycating agent for histones.  A downstream event of this reaction is the formation of advanced glycation endproducts (AGE).  We are developing biomarkers for the early steps of these complex reactions and are searching for drugs to inhibit these processes.  Another consequence of UV radiation and metabolism in general is the formation of reactive carbonyl species (carbonylation of proteins) that ultimately leads to formation of AGE.  The goal is to identify topical agents that will protect skin cells by limiting such deleterious reactions.  The laboratory uses a number of skin models including cultured fibroblasts and keratinocytes, nude mice, and nude guinea pigs, and transgenic mice.  We also are designing formulations of protective pro-nutrients and prodrugs that target delivery to the cellular layers of skin.  Techniques include analytical methods such as HPLC to identify biomarkers, screening assays that use visible-, UV-, and fluorescent- microwell plate readers to identify inhibitors of AGE formation, fluorescence microscopy comet assays to measure DNA damage and repair, and assays to assess bioconversion of prodrugs in the skin to active agents at the desired site.

Publications (Query PubMed for this investigator)

Gensler, H L., Williams, T., Huang, A. C., and Jacobson, E. L.  Oral Niacin Prevents Photocarcinogenesis and Photoimmunosuppression in Mice.  Nutrition and Cancer 34, 36-41, 2000

Katschinski, D.M., Jacobson, E.L., Wiedemann, G.J., and Robins, H.I.:  Modulation of VP-16 Cytotoxicity by Carboplatin and 41.8° C Hyperthermia.  J. Cancer Res and Clinical Oncol.,  2000, in press.

Wondrak, G.T., Cervantes-Laurean, D., Jacobson, E.L., and Jacobson, M.K.: Histone Carbonylation in vivo and in vitro.  Biochemical Journal 351: 769-777, 2000.

Jacobson, M.K., and Jacobson, E.L.: Discovering New ADP-ribose Polymer Cycles: Protecting the Genome and More. Trends in Biochemical Sciences:24, 415-417, 1999.

Jacobson, E.L., Shieh, W.M., and Huang, A.C.  Mapping the Role of NAD Metabolism in Cancer Prevention and Treatment.  Mol. Cell. Biochem., 193, 69-74, 1999

Robins, H. I., Tutsch, K., Ksatashinski, D. M., Jacobson, E. L., Mehta, M., Olsen, M., Cohen, J. D., Tiggelaar, C. L., Arzoomanian, R. Z., Alberti, D., Feierabend, C., Wilding, G.  A Phase I Trial of Intravenous Thymidine and Carboplatin in Patients with Advanced Cancer.  J of Clinical Oncology, 17, 2922-2931, 1999

Shieh, W.M., Amé , J.C., Wilson, M.V., Wang, Z.Q., Koh, D.W., Jacobson, M.K., and Jacobson, E.L.: Poly(ADP-ribose) Polymerases Null Mouse Cells Synthesize ADP-ribose Polymers. Journal of Biological Chemistry 273: 30069-30072, 1998.

Close This Window