I explore the processes that cells use to turn genes on and off. My work is focused on understanding a relatively new class of cellular pathways, governed by molecules known as small RNAs, that control gene activation and repression. Our studies of small-RNA biology in early development provide insights into human evolution, diversity, and diseases such as cancer.
Gregory Hannon is a pioneer in the study of RNA interference (RNAi), a process in which double-stranded RNA molecules induce gene silencing. Hannon and colleagues have elucidated key elements of the RNAi machinery. During the past several years, the Hannon lab has focused on the roles of small RNAs in germ cells, which tend to have the most elaborate set of small RNA pathways of any cell type. They have discovered an essential role for small RNAs, called Piwi-interacting RNAs (piRNAs), that are critical for proper oocyte development and guard the genome against transposable elements. This year, the lab conducted two screens, one in the fruit fly germline and another in somatic cells, to search for new components of the pathway that generates piRNAs. They identified dozens of genes that are required for piRNA production, offering insight into how germ cells ensure genomic integrity. The Hannon lab also strives to understand the biology of cancer cells, with a focus on breast and pancreatic cancer. They have led the way in using RNAi to study cancer biology and genetics, generating libraries of short-hairpin RNAs (shRNAs) that have been widely applied in gene-silencing studies. These libraries can then be used to identify new therapeutic targets for specific disease subtypes. In addition, they are exploring the roles of small RNAs as oncogenes and tumor suppressors and using genetic approaches to understand the biology of resistance to currently used cancer therapies. Another research thrust of Hannon’s team exploits the power of next-generation sequencing to understand the biology of the mammalian genome. Their efforts range from the identification of new classes of small RNAs to understanding human evolution and diversity, including an emphasis on the evolution of the epigenome and its role in driving cell-fate specification.
Cheloufi, S. and Dos Santos, C. O. and Chong, M. M. W. and Hannon, G. J. (2010) A Dicer-independent miRNA biogenesis pathway that requires Ago catalysis. Nature, 465(7298) pp. 584-U76.
Burbano, H. A. and Hodges, E. and Green, R. E. and Briggs, A. W. and Krause, J. and Meyer, M. and Good, J. M. and Maricic, T. and Johnson, P. L. F. and Xuan, Z. Y. and Rooks, M. and Bhattacharjee, A. and Brizuela, L. and Albert, F. W. and De La Rasilla, M. and Fortea, J. and Rosas, A. and Lachmann, M. and Hannon, G. J. and Paabo, S. (2010) Targeted investigation of the neandertal genome by array-based sequence capture. Science, 328(5979) pp. 723-725.
Malone, C. D. and Brennecke, J. and Dus, M. and Stark, A. and McCombie, W. R. and Sachidanandam, R. and Hannon, G. J. (2009) Specialized piRNA Pathways Act in Germline and Somatic Tissues of the Drosophila Ovary. Cell, 137(3) pp. 522-535 .
Czech, B. and Zhou, R. and Erlich, Y. and Brennecke, J. and Binari, R. and Villalta, C. and Gordon, A. and Perrimon, N. and Hannon, G. J. (2009) Hierarchical Rules for Argonaute Loading in Drosophila. Molecular Cell, 36(3) pp. 445-456.
Brennecke, J. and Aravin, A. A. and Stark, A. and Dus, M. and Kellis, M. and Sachidanandam, R. and Hannon, G. J. (2007) Discrete small RNA-generating loci as master regulators of transposon activity in Drosophila. Cell, 128(6) pp. 1089-103.Additional materials of the author at
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