David L. Spector

David L. Spector

Robert B. Gardner, Jr. Professor
Cancer Center Program Co-Leader

Ph.D., Rutgers University, 1980

spector@cshl.edu | 516-367-8456

Spector Lab Website   Faculty Profile

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.

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Selected Publications

Mammary Tumor-Associated RNAs Impact Tumor Cell Proliferation, Invasion, and Migration

27 Sep 2016 | Cell Reports | 17(1):261-274
Diermeier, Sarah, Chang, Kung-Chi, Freier, Susan, Song, Junyan, El Demerdash, Osama, Krasnitz, Alexander, Rigo, Frank, Bennett, C, Spector, David

Regulation of the ESC transcriptome by nuclear long non-coding RNAs

Sep 2015 | Genome Research | 25(9):1336-1346
Bergmann, J, Li, J, Eckersley-Maslin, M, Rigo, F, Freier, S, Spector, D

Random Monoallelic Gene Expression Increases upon Embryonic Stem Cell Differentiation

24 Feb 2014 | Developmental Cell | 28(4):351-65
Eckersley-Maslin, M, Thybert, D, Bergmann, J, Marioni, J, Flicek, P, Spector, D

The lncRNA Malat1 is dispensable for mouse development but its transcription plays a cis-regulatory role in the adult

2012 | Cell Reports | 2(1):111-123
Zhang, B, Arun, G, Mao, Y, Lazar, Z, Hung, G, Bhattacharjee, G, Xiao, X, Booth, C, Wu, J, Zhang, C, Spector, D

All Publications

MARK2/MARK3 kinases are catalytic co-dependencies of YAP/TAZ in human cancer

28 Feb 2024 | bioRxiv
Klingbeil, Olaf, Skopelitis, Damianos, Tonelli, Claudia, Alpsoy, Aktan, Minicozzi, Francesca, Aggarwal, Disha, Russo, Suzanne, Ha, Taehoon, Demerdash, Osama, Spector, David, Tuveson, David, Cifani, Paolo, Vakoc, Christopher

Chronic stress increases metastasis via neutrophil-mediated changes to the microenvironment

13 Feb 2024 | Cancer Cell
He, Xue-Yan, Gao, Yuan, Ng, David, Michalopoulou, Evdokia, George, Shanu, Adrover, Jose, Sun, Lijuan, Albrengues, Jean, Daßler-Plenker, Juliane, Han, Xiao, Wan, Ledong, Wu, Xiaoli, Shui, Longling, Huang, Yu-Han, Liu, Bodu, Su, Chang, Spector, David, Vakoc, Christopher, Van Aelst, Linda, Egeblad, Mikala

A sub-set of guanine- and cytosine-rich genes are actively transcribed at the nuclear Lamin B1 region

28 Oct 2023 | bioRxiv
Balasooriya, Gayan, Wee, Tse-Luen, Spector, David

Identification of glioblastoma stem cell-associated lncRNAs using single-cell RNA sequencing datasets

20 Oct 2023 | Stem Cell Reports
Hazra, Rasmani, Utama, Raditya, Naik, Payal, Dobin, Alexander, Spector, David

Neutrophil extracellular traps formed during chemotherapy confer treatment resistance via TGF-β activation

10 Apr 2023 | Cancer Cell | 41(4):757-775.e10
Mousset, Alexandra, Lecorgne, Enora, Bourget, Isabelle, Lopez, Pascal, Jenovai, Kitti, Cherfils-Vicini, Julien, Dominici, Chloé, Rios, Géraldine, Girard-Riboulleau, Cédric, Liu, Bodu, Spector, David, Ehmsen, Sidse, Renault, Shufang, Hego, Caroline, Mechta-Grigoriou, Fatima, Bidard, François-Clément, Terp, Mikkel, Egeblad, Mikala, Gaggioli, Cédric, Albrengues, Jean

Allele pairing at Sun1-enriched domains at the nuclear periphery via T1A3 tandem DNA repeats

7 Apr 2023 | bioRxiv
Balasooriya, Gayan, Spector, David

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