Greg Hannon, Ph.D., Cold Spring Harbor Laboratory

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The Hannon laboratory uses a wide variety of model systems to decipher the underlying biochemical mechanisms of RNA interference and uses that knowledge to design ways to harness the power of RNAi as a genetic tool in mammals.

Gregory Hannon
Professor
Investigator, Howard Hughes Medical Institute
Ph.D., Case Western Reserve University,1992
Growth control in mammalian cells; post-transcriptional gene silencing

email hannon@cshl.edu, phone (516) 367-8455, fax (516) 367-8874

Double-stranded RNA (dsRNA) triggers a sequence specific gene
silencing response known as RNA
interference or RNAi. RNAi is a conserved biological pathway that can be found in plants, animals and fungi.

We approach RNAi from several perspectives. We use model systems to illuminate the underlying biochemical pathways that respond to dsRNA and silence gene expression. Critical components of the RNAi machinery have been identified, including Dicer, which initiates silencing by processing double-stranded RNAs into the small RNAs that are the specificity components of the pathway. We also identified RISC, the effector complex of RNAi that uses the small RNAs as a guide to identify its targets. We are working to understand precisely how RISC silences its target through different effector mechanisms. RISC can suppress gene expression by destroying target mRNAs, by blocking their translation, or by preventing their transcription. Using biochemical, genetic, and structural approaches (in collaboration with L. Joshua-Tor at CSHL), we have found that one of these effector mechanisms is driven by the ability of a key RISC component (Argonaute) to catalyze mRNA cleavage. In mammals, we also explore the global functions of the RNAi machinery and the functions of endogenously encoded small RNAs, including microRNAs and our newly identified piRNAs.

As our understanding of the biology and biochemistry of RNAi deepens, we have worked to harness this pathway as a tool for probing gene function in mammals. We are working to apply the RNAi pathway as a tool to unravel oncogene and tumor suppressor pathways and to identify new anticancer targets.

Selected Publications

Brennecke, J., Aravin, A.A., Stark, A., Dus, M., Kellis, M., Sachidanandam, R., and Hannon, G.J. 2007. Discrete small RNA-generating loci as master regulators of transposon acitivity in Drosophila. Cell 128: 1089–1103.

Girard, A., Sachidanandam, R., Hannon, G.J., and Carmell, M.A. 2006. A germline-specific class of small RNAs binds mammalian Piwi proteins. Nature 442: 199–202.

He X., He L., Hannon G.J. 2004 The guardian’s little helper: microRNAs in the p53 tumor suppressor network. Cancer Research 67:11099-101.

Liu, J., Carmell, M.A., Rivas, F.V., Marsden, C.G., Thomson, J.M., Song, J.-J., Hammond, S.M., Joshua-Tor, L., and Hannon, G.J. 2004. Argonaute2 is the catalytic engine of mammalian RNAi. Science 305: 1437–1441.

Paddison, P.J., Silva, J.M., Conklin, D.S., Schlabach, M., Li, M., Aruleba, S., Balija, V., O’Shaughnessy, A., Gnoj, L., Scobie, K., Chang, K., Westbrook, T., Cleary, M., Sachidanandam, R., McCombie, W.R., Elledge, S.J., and Hannon, G.J. 2004. A resource for large-scale RNAi based screens in mammals. Nature 428: 427–431.