Robert Nicolosi, School of Health and Environment
To elucidate DNA damage response in human breast, skin and skin melanoma, this study applied an integrative approach which included classical genomic, microarray and refined computational systems biology approaches to study the regulatory pathways that involve DNA damaging associated with typical drug preparations of Tamoxifen (TAM) and the regulatory network that is affected by Dacarbazine (DAC).
Comparisons were made with the typical suspension preparations of TAM in contrast to the newly formulated nano-emulsions of both drugs. Specifically, after phenotypic screening was used to identify a set of transcription factors important for DNA damage response, the implicated regulatory pathways were systematically investigated using chromatin immunoprecipitation (CHIP) and DNA microarrays to monitor protein-DNA interactions as well as genome-wide expression patterns in cultured cell strains. These data were integrated and modeled using tools for comparison of networks across multiple cell treatments and for statistical identification of expression-activated network regions and pathways. Using this systems approach and the comparisons with nanoemulsion preparations of these drugs, the study generated new hypotheses revealing the complex web of interactions, cellular factors and mechanisms involved in DNA damage response induced by typical conventional cancer interventions.