David L. Spector

David L. Spector

Professor & Director of Research
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

Patient-derived triple-negative breast cancer organoids provide robust model systems that recapitulate tumor-intrinsic characteristics

18 Feb 2022 | Cancer Research
Bhatia, Sonam, Kramer, Melissa, Russo, Suzanne, Naik, Payal, Arun, Gayatri, Brophy, Kyle, Andrews, Peter, Fan, Cheng, Perou, Charles, Preall, Jonathan, Ha, Taehoon, Plenker, Dennis, Tuveson, David, Rishi, Arvind, Wilkinson, John, McCombie, W, Kostroff, Karen, Spector, David

Noncoding RNAs: biology and applications-a Keystone Symposia report.

17 Nov 2021 | Annals of the New York Academy of Sciences
Cable, Jennifer, Heard, Edith, Hirose, Tetsuro, Prasanth, Kannanganattu, Chen, Ling-Ling, Henninger, Jonathan, Quinodoz, Sofia, Spector, David, Diermeier, Sarah, Porman, Allison, Kumar, Dhiraj, Feinberg, Mark, Shen, Xiaohua, Unfried, Juan, Johnson, Rory, Chen, Chun-Kan, Wilusz, Jeremy, Lempradl, Adelheid, McGeary, Sean, Wahba, Lamia, Pyle, Anna, Hargrove, Amanda, Simon, Matthew, Marcia, Marco, Przanowska, Róża, Chang, Howard, Jaffrey, Samie, Contreras, Lydia, Chen, Qi, Shi, Junchao, Mendell, Joshua, He, Lin, Song, Erwei, Rinn, John, Lalwani, Mukesh, Kalem, Murat, Chuong, Edward, Maquat, Lynne, Liu, Xuhang

Activating a collaborative innate-adaptive immune response to control metastasis.

1 Sep 2021 | Cancer Cell
Sun, Lijuan, Kees, Tim, Almeida, Ana, Liu, Bodu, He, Xue-Yan, Ng, David, Han, Xiao, Spector, David, McNeish, Iain, Gimotty, Phyllis, Adams, Sylvia, Egeblad, Mikala

Patient-derived triple negative breast cancer organoids provide robust model systems that recapitulate tumor intrinsic characteristics

10 Aug 2021 | bioRxiv
Bhatia, Sonam, Kramer, Melissa, Russo, Suzanne, Naik, Payal, Arun, Gayatri, Brophy, Kyle, Andrews, Peter, Fan, Cheng, Perou, Charles, Preall, Jonathan, Ha, Taehoon, Rishi, Arvind, Wilkinson, John, McCombie, William, Kostroff, Karen, Spector, David

PHAROH lncRNA regulates Myc translation in hepatocellular carcinoma via sequestering TIAR.

18 May 2021 | eLife | 10
Yu, Allen, Berasain, Carmen, Bhatia, Sonam, Rivera, Keith, Liu, Bodu, Rigo, Frank, Pappin, Darryl, Spector, David

MaTAR25: a long non-coding RNA involved in breast cancer progression

1 Jan 2021 | Molecular and Cellular Oncology | 8(2):1882286
Chang, K, Spector, D

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