David L. Spector
Director of Research and Professor
Ph.D., Rutgers University, 1980
Cell biology; gene expression; nuclear structure; microscopy; non-coding RNAs
Research in my laboratory centers on understanding the spatial organization and regulation of gene expression within the context of the mammalian cell nucleus. In order to study the spatial and temporal aspects of gene expression we developed a live-cell gene expression system that allows 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. We are also using this approach to assess the transcription of single copy endogenous genes. In addition, since embryonic stem cells cells undergo dramatic changes in transcription, chromatin structure, and nuclear architecture as they transition from a pluripotent to a lineage specific cellular program we are studying the dynamic movements and expression of critical genes during the onset of ES cell differentiation.
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. We are focusing our efforts on a class of non-coding RNAs that are long (>1 kb) and retained in the nuclei of mammalian cells. We suggest that within this class of non-coding RNAs will be found a diverse group of key regulatory molecules that will provide significant insight into basic cellular functions, developmental regulation, and disease. Such non-coding RNAs may play a much more crucial role in physiological and pathological processes than currently anticipated. For example, mutations in non-coding regulatory RNAs may give rise to some of the phenotypes associated with specific diseases by altering gene expression at a specific locus or at a more global level. We are currently pursuing the function of several nuclear retained non-coding RNAs and are carrying out screens to identify other interesting candidates.
Please visit the Spector Laboratory home page.
Eckersley-Maslin, M.A., Bergmann, J.H., Lazar, Z. and Spector, D.L. 2013. Lamin A/C is expressed in pluripotent mouse embryonic stem cells. Nucleus 4: 53–60.
Zhang, B., Arun, G., Mao, Y.S., Lazar, Z., Hung, G., Bhattacharjee, G., Xiao, X., Booth, C.J., Wu, J., Zhang, C. and Spector, D.L. 2012. The lncRNA Malat1 is dispensable for mouse development but its transcription plays a cis-regulatory role in the adult. Cell Rep. 2: 111–123.
Zhao, R., Nakamura, T., Fu, Y., Lazar, Z., and Spector, D.L. 2011. Gene bookmarking accelerates the kinetics of post-mitotic transcriptional re-activation. Nat. Cell Biol. 13: 1295–1304.
Wilusz, J.E., Freier, S.M., and Spector, D.L. 2008. 3’ end processing of a long nuclear-retained non-coding RNA yields a tRNA-like cytoplasmic RNA. Cell 135: 919-932.
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.