Dorothea Becker, Ph.D.
Department of Pathology
Co-leader - UPCI Melanoma Program
University of Pittsburgh
HCC Suite 1.46
5117 Centre Avenue
Pittsburgh, PA 15213-1863
Research conducted in my laboratory focuses upon the identification and functional analysis of genes that govern melanoma development and progression. The stages defining melanoma progression are: atypical nevi - melanoma in situ - primary melanoma in the radial growth phase (RGP melanoma) - primary melanoma in the vertical growth phase (VGP melanoma) - melanoma in the metastatic growth phase (MGP melanoma). To unravel the molecular signature of the nevocytic and melanocytic lesions defining these stages, we have performed Serial Analysis of Gene Expression (SAGE), and whole-human genome microarray and proteomic profiling. The results of the whole-human genome microarray analysis of tissue samples ranging from normal skin to melanoma-infiltrated lymph nodes revealed two molecular profiles - one that characterizes normal skin, benign and atypical nevi, and melanoma in situ, and the other, VGP and MGP melanomas, including melanoma-infiltrated lymph nodes. Furthermore, the data from these whole-human genome microarray studies documented that the most prominent events associated with this switch from one molecular profile to the other, are aberrant changes in the mitotic cell cycle. Using molecular studies, including RNA interference, antisense technology, gene targeting with small molecule inhibitors as well as optical imaging, we are determining both in vitro and in preclinical studies involving human melanoma xenografts, the role of genes identified by these high-throughput studies in advanced-stage melanoma.
Bhattacharya C, Wang X, Becker D (2012). The DEAD/DEAH box helicase, DDX11, is essential for the survival of advanced melanomas. Mol. Cancer 11: 82.
Abdullah C, Wang X, Becker D (2011). Expression analysis and molecular targeting of cyclin-dependent kinases in advanced melanoma. Cell Cycle 10: 977-988.
Wang X, Moschos SJ, Becker D (2010). Functional analysis and molecular targeting of Aurora kinases A and B in advanced melanoma. Genes & Cancer 1: 952-963.
Botelho MG, Wang X, Arndt-Jovin DJ, Becker D, Jovin TM (2010). Induction of terminal differentiation in melanoma cells on downregulation of beta-amyloid precursor protein. J Invest. Dermatol. 130: 1400-1410.
Moschos SJ, Dodd NR, Jukic DM, Fayewicz SL, Wang X, Becker D (2009). Suppressing the high-level expression and function of ATM in advanced-stage melanomas does not sensitize the cells to ionizing radiation. Cancer Biol. Ther. 8: 1815-1825.
Moschos SJ, Pfaff Smith A, Mandic M, Athanassiou C, Watson-Hurst K, Jukic DM, Edington HD, Kirkwood JM, Becker D (2007). SAGE and antibody array analysis of melanoma-infiltrated lymph nodes: identification of Ubc9 as an important molecule in advanced-stage melanomas. Oncogene 26: 4216-4225.