David L. Spector
Ph.D., Rutgers University, 1980
The immense amount of DNA, RNA and proteins that contribute to our genetic programs are precisely organized inside the cell¹s nucleus. My group studies how nuclear organization impacts gene regulation, and how misregulation of non-coding RNAs contributes to human diseases such as cancer.
David L. Spector’s laboratory studies the spatial organization and regulation of gene expression. Their recent studies demonstrated an increase in random monoallelic gene expression upon the differentiation of mouse embryonic stem cells (mESCs) to neural progenitor cells (NPCs). These data support a model where stochastic gene regulation during differentiation results in monoallelic gene expression, and for some genes, the cell is able to compensate transcriptionally to maintain the required transcriptional output of these genes. Therefore, random monoallelic gene expression exemplifies the stochastic and plastic nature of gene expression in single cells. In addition, the Spector lab is characterizing long nuclear retained noncoding RNAs (lncRNAs) that exhibit altered levels of expression as mESCs transition from the pluripotent state to NPCs, and they are studying lncRNAs that are misregulated in cancer. Their efforts have focused on Malat1 lncRNA, which is one of the most abundant noncoding RNAs. The Spector lab previously identified a novel mechanism of 3′-end processing of this RNA. Current studies have revealed that altered levels of Malat1 lncRNA impact breast cancer initiation and progression. Studies are currently under way to elucidate the mechanism of action of this abundant nuclear retained lncRNA.
Building publication list.
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.
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.
Like mom or like dad? Some cells randomly express one parent’s version of a gene over the other
February 24, 2014
Study shows how “bookmarking” genes before cell division accelerates their subsequent reactivation
CSHL study finds that a pair of non-coding RNAs triggers formation of a nuclear subcompartment
Dr. David Spector, CSHL Professor, is elected to European Molecular Biology Organization