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David L. Spector Director of Research Professor Ph.D., Rutgers University, 1980 Cell biology; gene expression; nuclear structure; microscopy email spector@cshl.edu, phone (516) 367-8456, fax (516) 367-8876
We have developed a live-cell gene expression system allowing us to visualize a stably integrated regulatable genetic locus, and follow in real-time transcription of that locus, including visualization of its mRNA and protein products in living cells. Using this system we are examining the recruitment of members of the gene expression and silencing machineries. In addition, we are studying the exchange of critical factors at the site of this specific gene locus as it enters into and exits from mitosis. A second focus of my laboratory is to identify novel mechanisms of regulating gene expression with the ultimate goal of developing new approaches to understand and treat disease. In this regard, we have recently identified a “rapid response” mechanism of regulating gene expression. We identified a gene that produces a typical protein coding mRNA and a second RNA with a longer 3’ UTR containing signals that result in its nuclear retention. Upon physiologic stress this RNA is cleaved releasing the upstream protein-coding portion for transport to the cytoplasm. This “cut-and-run” response allows the cell to rapidly modulate protein levels more quickly than by initiating transcription. We are currently pursuing the identification and function of other large nuclear retained RNAs that are likely to serve as key regulatory molecules with significant impact on basic cellular functions, developmental regulation, and disease.
Please visit the Spector Laboratory home page.
Selected Publications Kumaran, R.I. and Spector, D.L. 2008. A genetic locus targeted to the nuclear periphery in living cells maintains its transcriptional competence. J. Cell Biol. 180: 51-65. Prasanth,K.V., Prasanth, S.G., Xuan, Z., Hearn, S., Freier, S.M., Bennett, C.F., Zhang, M.Q., and Spector, D.L. 2005. Regulating gene expression through RNA nuclear retention. Cell 123: 249–263. Janicki, S.M., Tsukamoto, T., Salghetti, S.E., Tansey, W.P., Sachidanandam, R., Prasanth, R.V., Ried, T., Shav-Tal, E., Bertrand, E., Singer, R.H., and Spector, D.L. 2004. From silencing to gene expression: Real-time analysis in single cells. Cell 116: 683–698. Tsukamoto, T., Hashiguchi, N., Janicki, S.M., Tumbar, T., Belmont, A.S., and Spector D.L. 2000.Visualization of gene activity in living cells. Nat. Cell Biol. 2: 871–878. Mintz, P.J., Patterson, S.D., Neuwald, A.F., Spahr, C.S., and Spector, D.L. 1999. Purification and biochemical characterization of interchromatin granule clusters. EMBO J. 18: 4308–4320.
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