The immense amount of DNA, RNA and proteins that contribute to our genetic programs are precisely organized inside the cell's 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 is focused on characterizing long non-coding RNAs (lncRNAs) that exhibit altered levels of expression in breast cancer progression and during embryonic stem cell differentiation. A major focus of their efforts has been on Malat1 lncRNA, which is one of the most abundant lncRNAs. The Spector lab previously identified a novel mechanism of 3′-end processing of this RNA. More recent studies have revealed that increased levels of Malat1 lncRNA impact breast cancer progression and metastasis. Knockout or antisense oligonucleotide knockdown of Malat1 results in the differentiation of mammary tumors and a significant reduction in metastasis. Studies are currently under way to elucidate the mechanism of action of this abundant nuclear retained lncRNA and to implement innovative therapeutic approaches that can impact its function in vivo. In addition, they have identified additional lncRNAs, termed Mammary Tumor Associated RNAs, that are upregulated in breast tumors, and they are currently assessing the function of these lncRNAs using 3D tumor organoids as well as mouse models.
A second area of study in the Spector lab is based on their earlier discovery of an increase in random autosomal monoallelic gene expression upon the differentiation of mouse embryonic stem cells to neural progenitor cells. 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. Ongoing studies are examining the relationship of monoallelic gene expression to lineage commitment.
Women’s coalition donates $100k to breast cancer research
December 6, 2018
Members of the Manhasset Women’s Coalition Against Breast Cancer supported research through a donation from the Ladies Night Out fundraiser.
Undergrad symposium highlights lessons in the lab
August 20, 2018
The 2018 Undergraduate Research Program class presents their projects after working for ten weeks in various labs across campus.
Portrait of a Neuroscience Powerhouse
April 27, 2018
A relatively small neuroscience group at CSHL is having an outsized impact on a dynamic and highly competitive field
David Spector is named ASCB Fellow
December 11, 2017
David L. Spector was named a fellow of The American Society for Cell Biology
CSHL to lead international team developing next-generation organoid cancer research
May 11, 2017
CSHL awarded a research subcontract by Leidos Biomedical Research to lead Cancer Model Development Center for upper-gastrointestinal cancers.
Cold Spring Harbor HS football player donates CSHL’s breast cancer research
December 13, 2016
Eli Gordon, kicker for the Cold Spring Harbor football team, presented a check today for $1,000.00 for breast cancer research.
Non-coding portions of genome are found to play role in cancer
September 27, 2016
CSHL scientists test an antisense method of targeting long noncoding RNAs overexpressed in breast cancers.
The WTFC Foundation supports breast cancer research at CSHL
June 6, 2016
The WTFC Foundation held its 10th Annual "The Breast of Everything" fundraiser, raising over $40,000 to support breast cancer research.
Unusual drug target and drug generate exciting preclinical results in mouse models of metastatic breast cancer
December 22, 2015
Researchers publish preclinical data suggesting the promise of a novel drug directed against a novel target n malignant mammary tumors.
Breaking down breast cancer at CSHL
October 30, 2015
A look at how several researchers at CSHL contribute to the field of breast cancer research.
Diermeier, Sarah D and Chang, Kung-Chi and Freier, Susan M and Song, Junyan and El Demerdash, Osama and Krasnitz, Alexander and Rigo, Frank and Bennett, C. Frank and Spector, David L (2016) Mammary Tumor-Associated RNAs Impact Tumor Cell Proliferation, Invasion, and Migration. Cell Reports, 17(1) pp. 261-274.
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.
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