David L. Spector
Professor & Director of Research
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.
Arun, G. and Diermeier, S. and Akerman, M. and Chang, K. C. and Wilkinson, J. E. and Hearn, S. and Kim, Y. and MacLeod, A. R. and Krainer, A. R. and Norton, L. and Brogi, E. and Egeblad, M. and Spector, D. L. (2016) Differentiation of mammary tumors and reduction in metastasis upon Malat1 lncRNA loss. Genes Dev 30(1) pp. 34-51.
Bergmann, J. H. and Li, J. and Eckersley-Maslin, M. A. and Rigo, F. and Freier, S. M. and Spector, D. L. (2015) Regulation of the ESC transcriptome by nuclear long non-coding RNAs. Genome Res 25(9) pp. 1336-1346.
Hogan, Megan S and Parfitt, David-Emlyn and Zepeda-Mendoza, Cinthya J and Shen, Michael M and Spector, David L (2015) Transient Pairing of Homologous Oct4 Alleles Accompanies the Onset of Embryonic Stem Cell Differentiation. Cell Stem Cell 16(3) pp. 275-288.
Eckersley-Maslin, M. A. and Thybert, D. and Bergmann, J. H. and Marioni, J. C. and Flicek, P. and Spector, D. L. (2014) Random Monoallelic Gene Expression Increases upon Embryonic Stem Cell Differentiation. Developmental Cell 28(4) pp. 351-65.
Zhang, B. and Arun, G. and Mao, Y. S. and Lazar, Z. and Hung, G. and Bhattacharjee, G. and Xiao, X. and Booth, C. J. and Wu, J. and 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 Reports 2(1) pp. 111-123.Additional materials of the author at
CSHL Institutional Repository
Unusual drug target and drug generate exciting preclinical results in mouse models of metastatic breast cancer
Breast cancer breakthrough
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