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 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
Manhasset Women’s Coalition Against Breast Cancer (MWCABC) has donated $100,000 to support breast cancer research at Cold Spring Harbor Laboratory. The donation supports the research of postdoctoral fellow Dr. Sonam Bhatia whose work focuses on developing new therapeutic targets for breast cancer using organoid technology. Members of the MWCABC’s Research Committee recently visited the Laboratory...
Undergrad symposium highlights lessons in the lab
August 20, 2018
The 2018 Undergraduate Research Program (URP) culminated in an end-of-the-summer symposium on August 9–10, with students presenting the results of their intensive 10-week research projects. Twenty students from universities all around the globe worked in the many labs across campus under the mentorship of Cold Spring Harbor Laboratory (CSHL) researchers in the fields of cancer...
Portrait of a Neuroscience Powerhouse
April 27, 2018
At noon every Tuesday from September through June, scenes from a revolution in neuroscience are playing out at Cold Spring Harbor Laboratory. Week after week, over 100 scientists cram themselves into a ground-floor meeting room in the Beckman Laboratory. It’s standing-room only as everyone in the Neuroscience Program settles in to hear details of the...
David Spector is named ASCB Fellow
December 11, 2017
David L. Spector, Ph.D., a professor at Cold Spring Harbor Laboratory (CSHL) and the Laboratory’s Director of Research, was named a fellow of The American Society for Cell Biology (ASCB). “This is a great honor, as the ASCB is the premiere society promoting scientific research, diversity in science, and advocating for public policy that impacts...
CSHL to lead international team developing next-generation organoid cancer research
May 11, 2017
Cold Spring Harbor Laboratory (CSHL) has been awarded a research subcontract by Leidos Biomedical Research to lead a Cancer Model Development Center
Cold Spring Harbor HS Football Player donates CSHL’s breast cancer research
December 13, 2016
Eli Gordon, kicker for the Cold Spring Harbor Seahawks Varsity Football Team, presented a check today for $1,000.00 for breast cancer research, as part of his “Kick Cancer” fundraising initiative, to Dr. David Spector, Director of Research and Professor at Cold Spring Harbor Labs. Gordon pledged $25 for every extra point he made this season;...
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 Cold Spring Harbor, NY — The human body produces 100,000 or more different proteins. Yet, amazingly, only two percent of the human genome actually encodes proteins. Nearly 80 percent of the rest of the genome is transcribed into RNA that...
The WTFC Foundation supports breast cancer research at CSHL
June 6, 2016
On May 13, The WTFC Foundation held its 10th Annual “The Breast of Everything” fundraiser, raising over $40,000 to support breast cancer research at top institutions across the country. Cold Spring Harbor Laboratory was selected as one of the recipients of these funds, and on June 2 the group’s founder and President Shari Goldsmith, visited...
Unusual drug target and drug generate exciting preclinical results in mouse models of metastatic breast cancer
December 22, 2015
Cold Spring Harbor, NY — A doctor treating a patient with a potentially fatal metastatic breast tumor would be very pleased to find, after administering a round of treatment, that the primary tumor had undergone a change in character—from aggressive to static, and no longer shedding cells that can colonize distant organs of the body....
Breaking down breast cancer at CSHL
October 30, 2015
LabDish blog Breast cancer awareness is important, but it’s action that saves lives. Whether developing more accurate and affordable tests for patients or mapping out the treacherous landscape of breast cancer genetics, researchers at CSHL certainly aren’t putting the fight on pause even as the pink ribbons dissipate. Explore how they’re attacking breast cancer from...
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