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.
Regulatory RNAs promote breast cancer metastasis
December 22, 2020
A gene-regulating bit of RNA promotes breast cancer metastasis. Agents that destroy that RNA provide hope for a new drug.
One experiment: Organoids as living laboratories
October 30, 2020
These tiny balls of cells are revolutionizing the research and treatment of pancreas and other types of cancers.
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.
What does it mean to be an URP?
August 20, 2018
A quick chat with a student and his mentor reveals how much the work of our undergraduate researchers mean to CSHL. Hint: A whole lot.
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
Breast cancer’s dark matter
July 21, 2017
Sarah Diermeier, Ph.D., talks about breast cancer and how Spector Lab are exploring the "dark matter of the genome" to find new ways to stop it.
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.
Base Pairs Episode 9: Dark matter of the genome, part 2
April 15, 2017
In this episode of Base Pairs, we question the mythos that is “junk DNA” and explore the mysterious non-coding portions of the genome.
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