Cold Spring Harbor Laboratory  
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Research Professor
Ph.D., Columbia University, 1983

Ph.D., Columbia University, 1983
Cancer genomics; functional genomics; cancer treatment

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Human cancers typically show extensive genomic alterations. Understanding these genomic alterations has been our primary interest for several years. Our discoveries include gene amplification and elucidation of the transforming properties of PPM1D, KCNK9, and the tyrosine kinase gene ACK1 in breast, ovarian and prostate adenocarcinomas, and identification of three genetically linked transcriptional factors that cooperate to transform cells in lung cancer.

The rapid advancement in genomic technologies has greatly expanded the number of known cancer-associated genomic alterations. To translate this wealth of information into new therapeutic targets has required scaling up functional studies.   To do this, we integrate cancer genome profiling with focused cDNA and RNAi screens to systematically search for driver genes and therapeutic targets.  Recently, we applied this approach to the study of hepatocellular carcinoma and discovered that amplification of FGF19 is not only oncogenic but is also a predictive biomarker to an antibody response, pinpointing a new targeted therapeutic strategy.

Cancer is a complex diseased tissue involving several cell types in addition to the genomically damaged cancer cells.  Additional targets for treating cancer may reside within these non-cancerous cells.  Towards this end, we have begun applying genomics to study the functional interaction of tumor cells with surrounding stromal fibroblasts.

Selected Publications

Li, J., Yang, Y., Peng, Y., Austin, R. J., van Eyndhoven, W. G., Nguyen, K. C., Gabriele, T., McCurrach, M. E., Marks, J. R., Hoey, T., Lowe, S. W. and Powers, S. 2002. Oncogenic properties of PPM1D located within a breast cancer amplification epicenter at 17q23. Nat Genet 31: 133-134.

van der Horst, E. H., Degenhardt, Y. Y., Strelow, A., Slavin, A., Chinn, L., Orf, J., Rong, M., Li, S., See, L. H., Nguyen, K. Q., Hoey, T., Wesche, H. and Powers, S. 2005. Metastatic properties and genomic amplification of the tyrosine kinase gene ACK1. Proc Natl Acad Sci U S A 102: 15901-15906.

Kendall, J., Liu, Q., Bakleh, A., Krasnitz, A., Nguyen, K. C., Lakshmi, B., Gerald, W. L., Powers, S. and Mu, D. 2007. Oncogenic cooperation and coamplification of developmental transcription factor genes in lung cancer. Proc Natl Acad Sci U S A 104: 16663-16668.

Zender, L., Xue, W., Zuber, J., Semighini, C. P., Krasnitz, A., Ma, B., Zender, P., Kubicka, S., Luk, J. M., Schirmacher, P., McCombie, W. R., Wigler, M., Hicks, J., Hannon, G. J., Powers, S. and Lowe, S. W. 2008. An oncogenomics-based in vivo RNAi screen identifies tumor suppressors in liver cancer. Cell 135: 852-864.

Sawey, E. T., Chanrion, M., Cai, C., Wu, G., Zhang, J., Zender, L., Zhao, A., Busuttil, R. W., Yee, H., Stein, L., French, D. M., Finn, R. S., Lowe, S. W. and Powers, S. 2011. Identification of a therapeutic strategy targeting amplified FGF19 in liver cancer by oncogenomic screening. Cancer Cell 19: 347-358.