Work in my laboratory focuses on the biology of RNAi and microRNAs. This biological pathway is becoming increasingly popular as a genetic tool. It is particularly valuable in mammalian cultured cells, where 'loss of function' methods were previously very restricted. Separate from its practical uses, the biology of RNAi is only beginning to be understood. This includes the exciting discovery that the RNAi pathway is used by cells to regulate their own genes via microRNAs.

Broadly speaking, my laboratory is pursuing three major lines of investigation:

1. Mechanistic study of RNAi.
My project as a postdoctoral associate in Greg Hannon's laboratory was a biochemical investigation into the mechanism of RNAi. In particular, we identified a Fragile X family member as a component of the RNAi machinery, raising the possibility that RNAi deficiency results in this human disease. My independent laboratory is continuing biochemical studies on the role of the Fragile X protein in the RNAi pathway. We are interested in the mechanism of translational suppression by microRNAs, and the possible connection between the RNAi pathway and chromatin regulation.

2. Cellular regulation by RNAi and microRNAs.
In C. elegans, Drosophila, and plants, microRNAs have been shown to play essential roles in gene regulation. Little is known about microRNA function in human cells. My laboratory is developing several genomic methods for analyzing microRNA function. We are particularly interested in maintenance of stem cell pluropotency, and growth control and transformation. We have identified several microRNAs that are correlated with these phenotypes, and are characterizing their cellular function.

3. Applications of RNAi to mammalian genetics.
The discovery of mammalian RNAi methods has enabled 'loss of function' studies in cultured cells. The typical application of this technology is for reverse genetics; that is, for knockdown of specific genes that are expected to be involved in a particular biologic process. Libraries of RNAi knockdown constructs that target approximately 8000 human genes are available to the research community. My laboratory is interested in developing these libraries for genetic screening approaches cell lines and animals. Our long term goal is the identification of novel therapeutic targets for cancer.

Hammond, S.M. MicroRNAs as oncogenes. Curr Opin Genet Dev, 16, 4-9 (2006).

He, L., Thomson, J.M., Hemann, M.T., Hernando-Monge, E., Mu, D., Goodson, S., Powers, S., Cordon-Cardo, C., Lowe, S.W., Hannon, G.J., Hammond, S.M. A microRNA polycistron as a potential human oncogene. Nature, 435, 828-833 (2005).

Thomson, J.M., Parker, J., Perou, C.M., Hammond, S.M. A custom microarray platform for analysis of microRNA gene expression, Nat. Methods, 1, 47-53 (2004).

Caudy, A.A., Myers, M., Hannon, G.J., Hammond, S.M. Fragile X related protein and VIG associate with the RNA interference machinery. Genes Dev, 16(19), 2491-2496 (2002).

Hammond, S.M., Boettcher, S., Caudy, A.A., Kobayashi, R., Hannon, G.J. Argonaute2, a link between genetic and biochemical analysis of RNAi. Science, 293, 1146-1150 (2001).

Hammond, S.M., Bernstein, E., Beach, D., Hannon, G.J. An RNA directed nuclease mediates post-transcriptional gene silencing in Drosophila cells. Nature 404, 293-296(2000).