Search

Your search keyword '"Denny, Sarah K."' showing total 22 results
Start Over Author "Denny, Sarah K."
22 results on '"Denny, Sarah K."'

3. Nfib Promotes Metastasis through a Widespread Increase in Chromatin Accessibility

Author

Denny, Sarah K, Yang, Dian, Chuang, Chen-Hua, Brady, Jennifer J, Lim, Jing Shan, Grüner, Barbara M, Chiou, Shin-Heng, Schep, Alicia N, Baral, Jessika, Hamard, Cécile, Antoine, Martine, Wislez, Marie, Kong, Christina S, Connolly, Andrew J, Park, Kwon-Sik, Sage, Julien, Greenleaf, William J, and Winslow, Monte M

Subjects
Biological Sciences, Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Human Genome, Cancer, Genetics, Lung Cancer, Lung, Aetiology, 2.1 Biological and endogenous factors, Amino Acid Motifs, Animals, Cell Line, Tumor, Cells, Cultured, Disease Models, Animal, Gene Expression Regulation, Neoplastic, Gene Knockdown Techniques, Humans, Lung Neoplasms, Mice, NFI Transcription Factors, Neoplasm Metastasis, Promoter Regions, Genetic, Small Cell Lung Carcinoma, Up-Regulation, Medical and Health Sciences, Developmental Biology, Biological sciences, Biomedical and clinical sciences
Abstract

Metastases are the main cause of cancer deaths, but the mechanisms underlying metastatic progression remain poorly understood. We isolated pure populations of cancer cells from primary tumors and metastases from a genetically engineered mouse model of human small cell lung cancer (SCLC) to investigate the mechanisms that drive the metastatic spread of this lethal cancer. Genome-wide characterization of chromatin accessibility revealed the opening of large numbers of distal regulatory elements across the genome during metastatic progression. These changes correlate with copy number amplification of the Nfib locus, and differentially accessible sites were highly enriched for Nfib transcription factor binding sites. Nfib is necessary and sufficient to increase chromatin accessibility at a large subset of the intergenic regions. Nfib promotes pro-metastatic neuronal gene expression programs and drives the metastatic ability of SCLC cells. The identification of widespread chromatin changes during SCLC progression reveals an unexpected global reprogramming during metastatic progression.

Published
2016

5. Supplementary_table_S5 from Intertumoral Heterogeneity in SCLC Is Influenced by the Cell Type of Origin

Author

Yang, Dian, primary, Denny, Sarah K., primary, Greenside, Peyton G., primary, Chaikovsky, Andrea C., primary, Brady, Jennifer J., primary, Ouadah, Youcef, primary, Granja, Jeffrey M., primary, Jahchan, Nadine S., primary, Lim, Jing Shan, primary, Kwok, Shirley, primary, Kong, Christina S., primary, Berghoff, Anna S., primary, Schmitt, Anna, primary, Reinhardt, H. Christian, primary, Park, Kwon-Sik, primary, Preusser, Matthias, primary, Kundaje, Anshul, primary, Greenleaf, William J., primary, Sage, Julien, primary, and Winslow, Monte M., primary

Published
2023
Full Text
View/download PDF

6. Supplementary Figure S1-S17 from Intertumoral Heterogeneity in SCLC Is Influenced by the Cell Type of Origin

Author

Yang, Dian, primary, Denny, Sarah K., primary, Greenside, Peyton G., primary, Chaikovsky, Andrea C., primary, Brady, Jennifer J., primary, Ouadah, Youcef, primary, Granja, Jeffrey M., primary, Jahchan, Nadine S., primary, Lim, Jing Shan, primary, Kwok, Shirley, primary, Kong, Christina S., primary, Berghoff, Anna S., primary, Schmitt, Anna, primary, Reinhardt, H. Christian, primary, Park, Kwon-Sik, primary, Preusser, Matthias, primary, Kundaje, Anshul, primary, Greenleaf, William J., primary, Sage, Julien, primary, and Winslow, Monte M., primary

Published
2023
Full Text
View/download PDF

7. Data from Intertumoral Heterogeneity in SCLC Is Influenced by the Cell Type of Origin

Author

Yang, Dian, primary, Denny, Sarah K., primary, Greenside, Peyton G., primary, Chaikovsky, Andrea C., primary, Brady, Jennifer J., primary, Ouadah, Youcef, primary, Granja, Jeffrey M., primary, Jahchan, Nadine S., primary, Lim, Jing Shan, primary, Kwok, Shirley, primary, Kong, Christina S., primary, Berghoff, Anna S., primary, Schmitt, Anna, primary, Reinhardt, H. Christian, primary, Park, Kwon-Sik, primary, Preusser, Matthias, primary, Kundaje, Anshul, primary, Greenleaf, William J., primary, Sage, Julien, primary, and Winslow, Monte M., primary

Published
2023
Full Text
View/download PDF

9. Multifaceted role for p53 in pancreatic cancer suppression

Author

Mello, Stephano S., primary, Flowers, Brittany M., additional, Mazur, Pawel K., additional, Lee, James J., additional, Müller, Fabian, additional, Denny, Sarah K., additional, Ferreira, Sofia, additional, Hanson, Kathryn, additional, Kim, Seung K., additional, Greenleaf, William J., additional, Wood, Laura D., additional, and Attardi, Laura D., additional

Published
2023
Full Text
View/download PDF

12. A Quantitative and Predictive Model for RNA Binding by Human Pumilio Proteins

Author

Jarmoskaite, Inga, primary, Denny, Sarah K., additional, Vaidyanathan, Pavanapuresan P., additional, Becker, Winston R., additional, Andreasson, Johan O.L., additional, Layton, Curtis J., additional, Kappel, Kalli, additional, Shivashankar, Varun, additional, Sreenivasan, Raashi, additional, Das, Rhiju, additional, Greenleaf, William J., additional, and Herschlag, Daniel, additional

Published
2019
Full Text
View/download PDF

14. Intertumoral Heterogeneity in SCLC Is Influenced by the Cell Type of Origin

Author

Yang, Dian, Denny, Sarah K., Greenside, Peyton G., Chaikovsky, Andrea C., Brady, Jennifer J., Ouadah, Youcef, Granja, Jeffrey M., Jahchan, Nadine S., Lim, Jing Shan, Kwok, Shirley, Kong, Christina S., Berghoff, Anna S., Schmitt, Anna, Reinhardt, H. Christian, Park, Kwon-Sik, Preusser, Matthias, Kundaje, Anshul, Greenleaf, William J., Sage, Julien, Winslow, Monte M., Yang, Dian, Denny, Sarah K., Greenside, Peyton G., Chaikovsky, Andrea C., Brady, Jennifer J., Ouadah, Youcef, Granja, Jeffrey M., Jahchan, Nadine S., Lim, Jing Shan, Kwok, Shirley, Kong, Christina S., Berghoff, Anna S., Schmitt, Anna, Reinhardt, H. Christian, Park, Kwon-Sik, Preusser, Matthias, Kundaje, Anshul, Greenleaf, William J., Sage, Julien, and Winslow, Monte M.

Abstract

The extent to which early events shape tumor evolution is largely uncharacterized, even though a better understanding of these early events may help identify key vulnerabilities in advanced tumors. Here, using genetically defined mouse models of small cell lung cancer (SCLC), we uncovered distinct metastatic programs attributable to the cell type of origin. In one model, tumors gain metastatic ability through amplification of the transcription factor NFIB and a widespread increase in chromatin accessibility, whereas in the other model, tumors become metastatic in the absence of NFIB-driven chromatin alterations. Gene-expression and chromatin accessibility analyses identify distinct mechanisms as well as markers predictive of metastatic progression in both groups. Underlying the difference between the two programs was the cell type of origin of the tumors, with NFIB-independent metastases arising from mature neuroendocrine cells. Our findings underscore the importance of the identity of cell type of origin in influencing tumor evolution and metastatic mechanisms. SIGNIFICANCE: We show that SCLC can arise from different cell types of origin, which profoundly influences the eventual genetic and epigenetic changes that enable metastatic progression. Understanding intertumoral heterogeneity in SCLC, and across cancer types, may illuminate mechanisms of tumor progression and uncover how the cell type of origin affects tumor evolution. (C) 2018 AACR.

Published
2018

16. Intertumoral Heterogeneity in SCLC Is Influenced by the Cell Type of Origin

Author

Yang, Dian, primary, Denny, Sarah K., additional, Greenside, Peyton G., additional, Chaikovsky, Andrea C., additional, Brady, Jennifer J., additional, Ouadah, Youcef, additional, Granja, Jeffrey M., additional, Jahchan, Nadine S., additional, Lim, Jing Shan, additional, Kwok, Shirley, additional, Kong, Christina S., additional, Berghoff, Anna S., additional, Schmitt, Anna, additional, Reinhardt, H. Christian, additional, Park, Kwon-Sik, additional, Preusser, Matthias, additional, Kundaje, Anshul, additional, Greenleaf, William J., additional, Sage, Julien, additional, and Winslow, Monte M., additional

Published
2018
Full Text
View/download PDF

17. A quantitative and predictive model for RNA binding by human Pumilio proteins

Author

Jarmoskaite, Inga, primary, Denny, Sarah K., additional, Vaidyanathan, Pavanapuresan P., additional, Becker, Winston R., additional, Andreasson, Johan O.L., additional, Layton, Curtis J., additional, Kappel, Kalli, additional, Shivashankar, Varun, additional, Sreenivasan, Raashi, additional, Das, Rhiju, additional, Greenleaf, William J., additional, and Herschlag, Daniel, additional

Published
2018
Full Text
View/download PDF

22. Linking RNA Sequence, Structure, and Function on Massively Parallel High-Throughput Sequencers.

Author

Denny SK and Greenleaf WJ

Subjects
Kinetics, Nucleic Acid Conformation, RNA metabolism, RNA-Binding Proteins metabolism, Thermodynamics, High-Throughput Nucleotide Sequencing methods, RNA chemistry
Abstract

High-throughput sequencing methods have revolutionized our ability to catalog the diversity of RNAs and RNA-protein interactions that can exist in our cells. However, the relationship between RNA sequence, structure, and function is enormously complex, demonstrating the need for methods that can provide quantitative thermodynamic and kinetic measurements of macromolecular interaction with RNA, at a scale commensurate with the sequence diversity of RNA. Here, we discuss a class of methods that extend the core functionality of DNA sequencers to enable high-throughput measurements of RNA folding and RNA-protein interactions. Topics discussed include a description of the method and multiple applications to RNA-binding proteins, riboswitch design and engineering, and RNA tertiary structure energetics., (Copyright © 2019 Cold Spring Harbor Laboratory Press; all rights reserved.)

Published
2019
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results