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1. In vivo CRISPR screens identify a dual function of MEN1 in regulating tumor–microenvironment interactions

Author

Su, Peiran, Liu, Yin, Chen, Tianyi, Xue, Yibo, Zeng, Yong, Zhu, Guanghui, Chen, Sujun, Teng, Mona, Ci, Xinpei, Guo, Mengdi, He, Michael Y., Hao, Jun, Chu, Vivian, Xu, Wenxi, Wang, Shiyan, Mehdipour, Parinaz, Xu, Xin, Marhon, Sajid A., Soares, Fraser, Pham, Nhu-An, Wu, Bell Xi, Her, Peter Hyunwuk, Feng, Shengrui, Alshamlan, Najd, Khalil, Maryam, Krishnan, Rehna, Yu, Fangyou, Chen, Chang, Burrows, Francis, Hakem, Razqallah, Lupien, Mathieu, Harding, Shane, Lok, Benjamin H., O’Brien, Catherine, Berlin, Alejandro, De Carvalho, Daniel D., Brooks, David G., Schramek, Daniel, Tsao, Ming-Sound, and He, Housheng Hansen

Published
2024
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2. Inhibiting EZH2 targets atypical teratoid rhabdoid tumor by triggering viral mimicry via both RNA and DNA sensing pathways

Author

Feng, Shengrui, Marhon, Sajid A., Sokolowski, Dustin J., D’Costa, Alister, Soares, Fraser, Mehdipour, Parinaz, Ishak, Charles, Loo Yau, Helen, Ettayebi, Ilias, Patel, Parasvi S., Chen, Raymond, Liu, Jiming, Zuzarte, Philip C., Ho, King Ching, Ho, Ben, Ning, Shiyao, Huang, Annie, Arrowsmith, Cheryl H., Wilson, Michael D., Simpson, Jared T., and De Carvalho, Daniel D.

Published
2024
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4. CRISPRi screens reveal a DNA methylation-mediated 3D genome dependent causal mechanism in prostate cancer.

Author

Ahmed, Musaddeque, Soares, Fraser, Xia, Ji-Han, Yang, Yue, Li, Jing, Guo, Haiyang, Su, Peiran, Tian, Yijun, Lee, Hyung Joo, Wang, Miranda, Akhtar, Nayeema, Houlahan, Kathleen E, Bosch, Almudena, Zhou, Stanley, Mazrooei, Parisa, Hua, Junjie T, Chen, Sujun, Petricca, Jessica, Zeng, Yong, Davies, Alastair, Fraser, Michael, Quigley, David A, Feng, Felix Y, Boutros, Paul C, Lupien, Mathieu, Zoubeidi, Amina, Wang, Liang, Walsh, Martin J, Wang, Ting, Ren, Shancheng, Wei, Gong-Hong, and He, Housheng Hansen

Subjects
Cell Line, Tumor, Animals, Mice, Inbred NOD, Humans, Mice, SCID, Prostatic Neoplasms, Genetic Predisposition to Disease, Proto-Oncogene Proteins c-myc, Risk Factors, DNA Methylation, Polymorphism, Single Nucleotide, Quantitative Trait Loci, Male, Regulatory Elements, Transcriptional, Promoter Regions, Genetic, Genome-Wide Association Study, Carcinogenesis, CRISPR-Cas Systems, Gene Editing, CCCTC-Binding Factor, Human Genome, Aging, Prostate Cancer, Urologic Diseases, Cancer, Genetics, 2.1 Biological and endogenous factors
Abstract

Prostate cancer (PCa) risk-associated SNPs are enriched in noncoding cis-regulatory elements (rCREs), yet their modi operandi and clinical impact remain elusive. Here, we perform CRISPRi screens of 260 rCREs in PCa cell lines. We find that rCREs harboring high risk SNPs are more essential for cell proliferation and H3K27ac occupancy is a strong indicator of essentiality. We also show that cell-line-specific essential rCREs are enriched in the 8q24.21 region, with the rs11986220-containing rCRE regulating MYC and PVT1 expression, cell proliferation and tumorigenesis in a cell-line-specific manner, depending on DNA methylation-orchestrated occupancy of a CTCF binding site in between this rCRE and the MYC promoter. We demonstrate that CTCF deposition at this site as measured by DNA methylation level is highly variable in prostate specimens, and observe the MYC eQTL in the 8q24.21 locus in individuals with low CTCF binding. Together our findings highlight a causal mechanism synergistically driven by a risk SNP and DNA methylation-mediated 3D genome architecture, advocating for the integration of genetics and epigenetics in assessing risks conferred by genetic predispositions.

Published
2021

5. Noncoding mutations target cis-regulatory elements of the FOXA1 plexus in prostate cancer.

Author

Zhou, Stanley, Hawley, James R, Soares, Fraser, Grillo, Giacomo, Teng, Mona, Madani Tonekaboni, Seyed Ali, Hua, Junjie Tony, Kron, Ken J, Mazrooei, Parisa, Ahmed, Musaddeque, Arlidge, Christopher, Yun, Hwa Young, Livingstone, Julie, Huang, Vincent, Yamaguchi, Takafumi N, Espiritu, Shadrielle MG, Zhu, Yanyun, Severson, Tesa M, Murison, Alex, Cameron, Sarina, Zwart, Wilbert, van der Kwast, Theodorus, Pugh, Trevor J, Fraser, Michael, Boutros, Paul C, Bristow, Robert G, He, Housheng Hansen, and Lupien, Mathieu

Subjects
Cell Line, Tumor, Humans, Prostatic Neoplasms, Transcription Factors, Cell Proliferation, Gene Expression Regulation, Neoplastic, Binding Sites, Regulatory Sequences, Nucleic Acid, Mutation, Male, Hepatocyte Nuclear Factor 3-alpha, Cell Line, Tumor, Gene Expression Regulation, Neoplastic, Regulatory Sequences, Nucleic Acid
Abstract

Prostate cancer is the second most commonly diagnosed malignancy among men worldwide. Recurrently mutated in primary and metastatic prostate tumors, FOXA1 encodes a pioneer transcription factor involved in disease onset and progression through both androgen receptor-dependent and androgen receptor-independent mechanisms. Despite its oncogenic properties however, the regulation of FOXA1 expression remains unknown. Here, we identify a set of six cis-regulatory elements in the FOXA1 regulatory plexus harboring somatic single-nucleotide variants in primary prostate tumors. We find that deletion and repression of these cis-regulatory elements significantly decreases FOXA1 expression and prostate cancer cell growth. Six of the ten single-nucleotide variants mapping to FOXA1 regulatory plexus significantly alter the transactivation potential of cis-regulatory elements by modulating the binding of transcription factors. Collectively, our results identify cis-regulatory elements within the FOXA1 plexus mutated in primary prostate tumors as potential targets for therapeutic intervention.

Published
2020

6. ONECUT2 is a driver of neuroendocrine prostate cancer.

Author

Guo, Haiyang, Ci, Xinpei, Ahmed, Musaddeque, Hua, Junjie Tony, Soares, Fraser, Lin, Dong, Puca, Loredana, Vosoughi, Aram, Xue, Hui, Li, Estelle, Su, Peiran, Chen, Sujun, Nguyen, Tran, Liang, Yi, Zhang, Yuzhe, Xu, Xin, Xu, Jing, Sheahan, Anjali V, Ba-Alawi, Wail, Zhang, Si, Mahamud, Osman, Vellanki, Ravi N, Gleave, Martin, Bristow, Robert G, Haibe-Kains, Benjamin, Poirier, John T, Rudin, Charles M, Tsao, Ming-Sound, Wouters, Bradly G, Fazli, Ladan, Feng, Felix Y, Ellis, Leigh, van der Kwast, Theo, Berlin, Alejandro, Koritzinsky, Marianne, Boutros, Paul C, Zoubeidi, Amina, Beltran, Himisha, Wang, Yuzhuo, and He, Housheng Hansen

Subjects
Prostate, Cell Line, Tumor, Animals, Mice, Inbred NOD, Humans, Mice, Mice, SCID, Neuroendocrine Tumors, Prostatic Neoplasms, Disease Progression, Phosphoramide Mustards, Nitroimidazoles, Homeodomain Proteins, Transcription Factors, RNA, Small Interfering, Xenograft Model Antitumor Assays, Gene Expression Profiling, Signal Transduction, Cell Proliferation, Cell Hypoxia, Gene Expression Regulation, Neoplastic, Up-Regulation, Male, Hypoxia-Inducible Factor 1, alpha Subunit, Smad3 Protein, Carcinogenesis, Datasets as Topic, Urologic Diseases, Cancer, Prostate Cancer, Aging, 2.1 Biological and endogenous factors, Cell Line, Tumor, Inbred NOD, SCID, RNA, Small Interfering, Gene Expression Regulation, Neoplastic, Hypoxia-Inducible Factor 1, alpha Subunit
Abstract

Neuroendocrine prostate cancer (NEPC), a lethal form of the disease, is characterized by loss of androgen receptor (AR) signaling during neuroendocrine transdifferentiation, which results in resistance to AR-targeted therapy. Clinically, genomically and epigenetically, NEPC resembles other types of poorly differentiated neuroendocrine tumors (NETs). Through pan-NET analyses, we identified ONECUT2 as a candidate master transcriptional regulator of poorly differentiated NETs. ONECUT2 ectopic expression in prostate adenocarcinoma synergizes with hypoxia to suppress androgen signaling and induce neuroendocrine plasticity. ONEUCT2 drives tumor aggressiveness in NEPC, partially through regulating hypoxia signaling and tumor hypoxia. Specifically, ONECUT2 activates SMAD3, which regulates hypoxia signaling through modulating HIF1α chromatin-binding, leading NEPC to exhibit higher degrees of hypoxia compared to prostate adenocarcinomas. Treatment with hypoxia-activated prodrug TH-302 potently reduces NEPC tumor growth. Collectively, these results highlight the synergy between ONECUT2 and hypoxia in driving NEPC, and emphasize the potential of hypoxia-directed therapy for NEPC patients.

Published
2019

9. Single-cell analysis reveals transcriptomic remodellings in distinct cell types that contribute to human prostate cancer progression

Author

Chen, Sujun, Zhu, Guanghui, Yang, Yue, Wang, Fubo, Xiao, Yu-Tian, Zhang, Na, Bian, Xiaojie, Zhu, Yasheng, Yu, Yongwei, Liu, Fei, Dong, Keqin, Mariscal, Javier, Liu, Yin, Soares, Fraser, Loo Yau, Helen, Zhang, Bo, Chen, Weidong, Wang, Chao, Chen, Dai, Guo, Qinghua, Yi, Zhengfang, Liu, Mingyao, Fraser, Michael, De Carvalho, Daniel D., Boutros, Paul C., Di Vizio, Dolores, Jiang, Zhou, van der Kwast, Theodorus, Berlin, Alejandro, Wu, Song, Wang, Jianhua, He, Housheng Hansen, and Ren, Shancheng

Published
2021
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11. Transcriptional landscape of the human cell cycle

Author

Liu, Yin, Chen, Sujun, Wang, Su, Soares, Fraser, Fischer, Martin, Meng, Feilong, Du, Zhou, Lin, Charles, Meyer, Clifford, DeCaprio, James A., Brown, Myles, Liu, X. Shirley, and He, Housheng Hansen

Published
2017

12. Supplementary Figures from LSD1-Mediated Epigenetic Reprogramming Drives CENPE Expression and Prostate Cancer Progression

Author

Liang, Yi, primary, Ahmed, Musaddeque, primary, Guo, Haiyang, primary, Soares, Fraser, primary, Hua, Junjie T., primary, Gao, Shuai, primary, Lu, Catherine, primary, Poon, Christine, primary, Han, Wanting, primary, Langstein, Jens, primary, Ekram, Muhammad B., primary, Li, Brian, primary, Davicioni, Elai, primary, Takhar, Mandeep, primary, Erho, Nicholas, primary, Karnes, R. Jeffrey, primary, Chadwick, Dianne, primary, van der Kwast, Theodorus, primary, Boutros, Paul C., primary, Arrowsmith, Cheryl H., primary, Feng, Felix Y., primary, Joshua, Anthony M., primary, Zoubeidi, Amina, primary, Cai, Changmeng, primary, and He, Housheng H., primary

Published
2023
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13. Data from LSD1-Mediated Epigenetic Reprogramming Drives CENPE Expression and Prostate Cancer Progression

Author

Liang, Yi, primary, Ahmed, Musaddeque, primary, Guo, Haiyang, primary, Soares, Fraser, primary, Hua, Junjie T., primary, Gao, Shuai, primary, Lu, Catherine, primary, Poon, Christine, primary, Han, Wanting, primary, Langstein, Jens, primary, Ekram, Muhammad B., primary, Li, Brian, primary, Davicioni, Elai, primary, Takhar, Mandeep, primary, Erho, Nicholas, primary, Karnes, R. Jeffrey, primary, Chadwick, Dianne, primary, van der Kwast, Theodorus, primary, Boutros, Paul C., primary, Arrowsmith, Cheryl H., primary, Feng, Felix Y., primary, Joshua, Anthony M., primary, Zoubeidi, Amina, primary, Cai, Changmeng, primary, and He, Housheng H., primary

Published
2023
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14. Excessive transcription-replication conflicts are a vulnerability of BRCA1-mutant cancers

Author

Patel, Parasvi S, primary, Algouneh, Arash, additional, Krishnan, Rehna, additional, Reynolds, John J, additional, Nixon, Kevin C J, additional, Hao, Jun, additional, Lee, Jihoon, additional, Feng, Yue, additional, Fozil, Chehronai, additional, Stanic, Mia, additional, Yerlici, Talya, additional, Su, Peiran, additional, Soares, Fraser, additional, Liedtke, Elisabeth, additional, Prive, Gil, additional, Baider, Gary D, additional, Pujana, Miquel Angel, additional, Mekhail, Karim, additional, He, Housheng Hansen, additional, Hakem, Anne, additional, Stewart, Grant S, additional, and Hakem, Razqallah, additional

Published
2023
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15. Excessive transcription-replication conflicts are a vulnerability of BRCA1-mutant cancers

Author

Patel, Parasvi S, Algouneh, Arash, Krishnan, Rehna, Reynolds, John J, Nixon, Kevin C J, Hao, Jun, Lee, Jihoon, Feng, Yue, Fozil, Chehronai, Stanic, Mia, Yerlici, Talya, Su, Peiran, Soares, Fraser, Liedtke, Elisabeth, Prive, Gil, Baider, Gary D, Pujana, Miquel Angel, Mekhail, Karim, He, Housheng Hansen, Hakem, Anne, Stewart, Grant S, Hakem, Razqallah, Patel, Parasvi S, Algouneh, Arash, Krishnan, Rehna, Reynolds, John J, Nixon, Kevin C J, Hao, Jun, Lee, Jihoon, Feng, Yue, Fozil, Chehronai, Stanic, Mia, Yerlici, Talya, Su, Peiran, Soares, Fraser, Liedtke, Elisabeth, Prive, Gil, Baider, Gary D, Pujana, Miquel Angel, Mekhail, Karim, He, Housheng Hansen, Hakem, Anne, Stewart, Grant S, and Hakem, Razqallah

Abstract

BRCA1 mutations are associated with increased breast and ovarian cancer risk. BRCA1-mutant tumors are high-grade, recurrent, and often become resistant to standard therapies. Herein, we performed a targeted CRISPR-Cas9 screen and identified MEPCE, a methylphosphate capping enzyme, as a synthetic lethal interactor of BRCA1. Mechanistically, we demonstrate that depletion of MEPCE in a BRCA1-deficient setting led to dysregulated RNA polymerase II (RNAPII) promoter-proximal pausing, R-loop accumulation, and replication stress, contributing to transcription-replication collisions. These collisions compromise genomic integrity resulting in loss of viability of BRCA1-deficient cells. We also extend these findings to another RNAPII-regulating factor, PAF1. This study identifies a new class of synthetic lethal partners of BRCA1 that exploit the RNAPII pausing regulation and highlight the untapped potential of transcription-replication collision-inducing factors as unique potential therapeutic targets for treating cancers associated with BRCA1 mutations.

Published
2023

17. 343: N6-METHYLADENOSINE READER YTHDF1 PROMOTES ARHGEF2 TRANSLATION AND RHOA SIGNALING IN COLORECTAL CANCER

Author

Wang, Shiyan, primary, Gao, Shanshan, additional, Zeng, Yong, additional, Zhu, Lin, additional, Wong, Chi Chun, additional, Bao, Yi, additional, Su, Peiran, additional, Zhai, Jianning, additional, Wang, Lina, additional, Soares, Fraser, additional, Xu, Xin, additional, Chen, Huarong, additional, Hezaveh, Kebria, additional, Mo, Yulin, additional, Ci, Xinpei, additional, He, Aobo, additional, McGaha, Tracy, additional, O'Brien, Catherine, additional, Rottapel, Robert, additional, Kang, Wei, additional, Wu, Jianfeng, additional, Zheng, Gang, additional, Cai, Zongwei, additional, Yu, Jun, additional, and He, Housheng Hansen, additional

Published
2022
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18. N6-Methyladenosine Reader YTHDF1 Promotes ARHGEF2 Translation and RhoA Signaling in Colorectal Cancer

Author

Wang, Shiyan, primary, Gao, Shanshan, additional, Zeng, Yong, additional, Zhu, Lin, additional, Mo, Yulin, additional, Wong, Chi Chun, additional, Bao, Yi, additional, Su, Peiran, additional, Zhai, Jianning, additional, Wang, Lina, additional, Soares, Fraser, additional, Xu, Xin, additional, Chen, Huarong, additional, Hezaveh, Kebria, additional, Ci, Xinpei, additional, He, Aobo, additional, McGaha, Tracy, additional, O’Brien, Catherine, additional, Rottapel, Robert, additional, Kang, Wei, additional, Wu, Jianfeng, additional, Zheng, Gang, additional, Cai, Zongwei, additional, Yu, Jun, additional, and He, Housheng Hansen, additional

Published
2022
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20. Colorectal Cancer Cells Enter a Diapause-like DTP State to Survive Chemotherapy

Author

Rehman, Sumaiyah S.K., Haynes, Jennifer, Collignon, Evelyne, Brown, Kevin K.R., Wang, Yadong, Nixon, Allison A.M.L., Bruce, Jeff J.P., Wintersinger, Jeff J.A., Singh Mer, Arvind, Lo, Edwyn E.B.L., Leung, Cherry, Lima-Fernandes, Evelyne, Pedley, Nicholas N.M., Soares, Fraser, McGibbon, Sophie, He, Housheng Hansen, Pollet, Aaron, Pugh, Trevor T.J., Haibe-Kains, Benjamin, Morris, Quaid, Ramalho-Santos, Miguel, Goyal, Sidhartha, Moffat, Jason, O'Brien, Catherine Adell, Rehman, Sumaiyah S.K., Haynes, Jennifer, Collignon, Evelyne, Brown, Kevin K.R., Wang, Yadong, Nixon, Allison A.M.L., Bruce, Jeff J.P., Wintersinger, Jeff J.A., Singh Mer, Arvind, Lo, Edwyn E.B.L., Leung, Cherry, Lima-Fernandes, Evelyne, Pedley, Nicholas N.M., Soares, Fraser, McGibbon, Sophie, He, Housheng Hansen, Pollet, Aaron, Pugh, Trevor T.J., Haibe-Kains, Benjamin, Morris, Quaid, Ramalho-Santos, Miguel, Goyal, Sidhartha, Moffat, Jason, and O'Brien, Catherine Adell

Abstract

Cancer cells enter a reversible drug-tolerant persister (DTP) state to evade death from chemotherapy and targeted agents. It is increasingly appreciated that DTPs are important drivers of therapy failure and tumor relapse. We combined cellular barcoding and mathematical modeling in patient-derived colorectal cancer models to identify and characterize DTPs in response to chemotherapy. Barcode analysis revealed no loss of clonal complexity of tumors that entered the DTP state and recurred following treatment cessation. Our data fit a mathematical model where all cancer cells, and not a small subpopulation, possess an equipotent capacity to become DTPs. Mechanistically, we determined that DTPs display remarkable transcriptional and functional similarities to diapause, a reversible state of suspended embryonic development triggered by unfavorable environmental conditions. Our study provides insight into how cancer cells use a developmentally conserved mechanism to drive the DTP state, pointing to novel therapeutic opportunities to target DTPs., SCOPUS: ar.j, info:eu-repo/semantics/published

Published
2021

23. Colorectal Cancer Cells Enter a Diapause-like DTP State to Survive Chemotherapy

Author

Rehman, Sumaiyah K., primary, Haynes, Jennifer, additional, Collignon, Evelyne, additional, Brown, Kevin R., additional, Wang, Yadong, additional, Nixon, Allison M.L., additional, Bruce, Jeffrey P., additional, Wintersinger, Jeffrey A., additional, Singh Mer, Arvind, additional, Lo, Edwyn B.L., additional, Leung, Cherry, additional, Lima-Fernandes, Evelyne, additional, Pedley, Nicholas M., additional, Soares, Fraser, additional, McGibbon, Sophie, additional, He, Housheng Hansen, additional, Pollet, Aaron, additional, Pugh, Trevor J., additional, Haibe-Kains, Benjamin, additional, Morris, Quaid, additional, Ramalho-Santos, Miguel, additional, Goyal, Sidhartha, additional, Moffat, Jason, additional, and O’Brien, Catherine A., additional

Published
2021
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25. Widespread and Functional RNA Circularization in Localized Prostate Cancer

Author

Chen, Sujun, primary, Huang, Vincent, additional, Xu, Xin, additional, Livingstone, Julie, additional, Soares, Fraser, additional, Jeon, Jouhyun, additional, Zeng, Yong, additional, Hua, Junjie Tony, additional, Petricca, Jessica, additional, Guo, Haiyang, additional, Wang, Miranda, additional, Yousif, Fouad, additional, Zhang, Yuzhe, additional, Donmez, Nilgun, additional, Ahmed, Musaddeque, additional, Volik, Stas, additional, Lapuk, Anna, additional, Chua, Melvin L.K., additional, Heisler, Lawrence E., additional, Foucal, Adrien, additional, Fox, Natalie S., additional, Fraser, Michael, additional, Bhandari, Vinayak, additional, Shiah, Yu-Jia, additional, Guan, Jiansheng, additional, Li, Jixi, additional, Orain, Michèle, additional, Picard, Valérie, additional, Hovington, Hélène, additional, Bergeron, Alain, additional, Lacombe, Louis, additional, Fradet, Yves, additional, Têtu, Bernard, additional, Liu, Stanley, additional, Feng, Felix, additional, Wu, Xue, additional, Shao, Yang W., additional, Komor, Malgorzata A., additional, Sahinalp, Cenk, additional, Collins, Colin, additional, Hoogstrate, Youri, additional, de Jong, Mark, additional, Fijneman, Remond J.A., additional, Fei, Teng, additional, Jenster, Guido, additional, van der Kwast, Theodorus, additional, Bristow, Robert G., additional, Boutros, Paul C., additional, and He, Housheng Hansen, additional

Published
2019
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28. Risk SNP-Mediated Promoter-Enhancer Switching Drives Prostate Cancer through lncRNA PCAT19

Author

Hua, Junjie Tony, primary, Ahmed, Musaddeque, additional, Guo, Haiyang, additional, Zhang, Yuzhe, additional, Chen, Sujun, additional, Soares, Fraser, additional, Lu, Jennifer, additional, Zhou, Stanley, additional, Wang, Miranda, additional, Li, Hui, additional, Larson, Nicholas B., additional, McDonnell, Shannon K., additional, Patel, Parasvi S., additional, Liang, Yi, additional, Yao, Cindy Q., additional, van der Kwast, Theodorus, additional, Lupien, Mathieu, additional, Feng, Felix Y., additional, Zoubeidi, Amina, additional, Tsao, Ming-Sound, additional, Thibodeau, Stephen N., additional, Boutros, Paul C., additional, and He, Housheng Hansen, additional

Published
2018
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29. LSD1-Mediated Epigenetic Reprogramming Drives CENPE Expression and Prostate Cancer Progression

Author

Liang, Yi, primary, Ahmed, Musaddeque, additional, Guo, Haiyang, additional, Soares, Fraser, additional, Hua, Junjie T., additional, Gao, Shuai, additional, Lu, Catherine, additional, Poon, Christine, additional, Han, Wanting, additional, Langstein, Jens, additional, Ekram, Muhammad B., additional, Li, Brian, additional, Davicioni, Elai, additional, Takhar, Mandeep, additional, Erho, Nicholas, additional, Karnes, R. Jeffrey, additional, Chadwick, Dianne, additional, van der Kwast, Theodorus, additional, Boutros, Paul C., additional, Arrowsmith, Cheryl H., additional, Feng, Felix Y., additional, Joshua, Anthony M., additional, Zoubeidi, Amina, additional, Cai, Changmeng, additional, and He, Housheng H., additional

Published
2017
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32. Modulation of long noncoding RNAs by risk SNPs underlying genetic predispositions to prostate cancer

Author

Guo, Haiyang, primary, Ahmed, Musaddeque, additional, Zhang, Fan, additional, Yao, Cindy Q, additional, Li, SiDe, additional, Liang, Yi, additional, Hua, Junjie, additional, Soares, Fraser, additional, Sun, Yifei, additional, Langstein, Jens, additional, Li, Yuchen, additional, Poon, Christine, additional, Bailey, Swneke D, additional, Desai, Kinjal, additional, Fei, Teng, additional, Li, Qiyuan, additional, Sendorek, Dorota H, additional, Fraser, Michael, additional, Prensner, John R, additional, Pugh, Trevor J, additional, Pomerantz, Mark, additional, Bristow, Robert G, additional, Lupien, Mathieu, additional, Feng, Felix Y, additional, Boutros, Paul C, additional, Freedman, Matthew L, additional, Walsh, Martin J, additional, and He, Housheng Hansen, additional

Published
2016
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34. Transcriptional landscape of the human cell cycle.

Author

Yin Liu, Sujun Chen, Su Wang, Soares, Fraser, Fischer, Martin, Feilong Meng, Zhou Du, Lin, Charles, Meyer, Clifford, DeCaprio, James A., Brown, Myles, Liu, X. Shirley, and Housheng Hansen He

Subjects
GENE regulatory networks, HUMAN cell cycle, CELL cycle, MAMMALIAN cell cycle, BREAST cancer
Abstract

Steady-state gene expression across the cell cycle has been studied extensively. However, transcriptional gene regulation and the dynamics of histone modification at different cell-cycle stages are largely unknown. By applying a combination of global nuclear run-on sequencing (GRO-seq), RNA sequencing (RNA-seq), and histonemodification Chip sequencing (ChIP-seq), we depicted a comprehensive transcriptional landscape at the G0/G1, G1/S, and M phases of breast cancer MCF-7 cells. Importantly, GRO-seq and RNA-seq analysis identified different cell-cycle–regulated genes, suggesting a lag between transcription and steady-state expression during the cell cycle. Interestingly, we identified genes actively transcribed at earlyMphase that are longer in length and have low expression and are accompanied by a global increase in active histone 3 lysine 4 methylation (H3K4me2) and histone 3 lysine 27 acetylation (H3K27ac) modifications. In addition, we identified 2,440 cell-cycle–regulated enhancer RNAs (eRNAs) that are strongly associated with differential active transcription but not with stable expression levels across the cell cycle. Motif analysis of dynamic eRNAs predicted Kruppel-like factor 4 (KLF4) as a key regulator of G1/S transition, and this identification was validated experimentally. Taken together, our combined analysis characterized the transcriptional and histone-modification profile of the human cell cycle and identified dynamic transcriptional signatures across the cell cycle. [ABSTRACT FROM AUTHOR]

Published
2017
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35. The Mitochondrial Protein NLRX1 Controls the Balance between Extrinsic and Intrinsic Apoptosis

Author

Soares, Fraser, primary, Tattoli, Ivan, additional, Rahman, Muhammed A., additional, Robertson, Susan J., additional, Belcheva, Antoaneta, additional, Liu, Daniel, additional, Streutker, Catherine, additional, Winer, Shawn, additional, Winer, Daniel A., additional, Martin, Alberto, additional, Philpott, Dana J., additional, Arnoult, Damien, additional, and Girardin, Stephen E., additional

Published
2014
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36. Peptidoglycan ld-Carboxypeptidase Pgp2 Influences Campylobacter jejuni Helical Cell Shape and Pathogenic Properties and Provides the Substrate for the dl-Carboxypeptidase Pgp1

Author

Frirdich, Emilisa, primary, Vermeulen, Jenny, additional, Biboy, Jacob, additional, Soares, Fraser, additional, Taveirne, Michael E., additional, Johnson, Jeremiah G., additional, DiRita, Victor J., additional, Girardin, Stephen E., additional, Vollmer, Waldemar, additional, and Gaynor, Erin C., additional

Published
2014
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37. Nod1 and Nod2 direct autophagy by recruiting ATG16L1 to the plasma membrane at the site of bacterial entry.

Author

Travassos, Leonardo H, Carneiro, Leticia A M, Ramjeet, Mahendrasingh, Hussey, Seamus, Kim, Yun-Gi, Magalhães, João G, Yuan, Linda, Soares, Fraser, Chea, Evelyn, Le Bourhis, Lionel, Boneca, Ivo G, Allaoui, Abdelmounaaim, Jones, Nicola L, Nuñez, Gabriel, Girardin, Stephen E, Philpott, Dana J, Travassos, Leonardo H, Carneiro, Leticia A M, Ramjeet, Mahendrasingh, Hussey, Seamus, Kim, Yun-Gi, Magalhães, João G, Yuan, Linda, Soares, Fraser, Chea, Evelyn, Le Bourhis, Lionel, Boneca, Ivo G, Allaoui, Abdelmounaaim, Jones, Nicola L, Nuñez, Gabriel, Girardin, Stephen E, and Philpott, Dana J

Abstract

Autophagy is emerging as a crucial defense mechanism against bacteria, but the host intracellular sensors responsible for inducing autophagy in response to bacterial infection remain unknown. Here we demonstrated that the intracellular sensors Nod1 and Nod2 are critical for the autophagic response to invasive bacteria. By a mechanism independent of the adaptor RIP2 and transcription factor NF-kappaB, Nod1 and Nod2 recruited the autophagy protein ATG16L1 to the plasma membrane at the bacterial entry site. In cells homozygous for the Crohn's disease-associated NOD2 frameshift mutation, mutant Nod2 failed to recruit ATG16L1 to the plasma membrane and wrapping of invading bacteria by autophagosomes was impaired. Our results link bacterial sensing by Nod proteins to the induction of autophagy and provide a functional link between Nod2 and ATG16L1, which are encoded by two of the most important genes associated with Crohn's disease., Journal Article, Research Support, N.I.H. Extramural, Research Support, Non-U.S. Gov't, SCOPUS: ar.j, info:eu-repo/semantics/published

Published
2010

42. Enhancement of Reactive Oxygen Species Production and Chlamydial Infection by the Mitochondrial Nod-like Family Member NLRX1

Author

Abdul-Sater, Ali A., primary, Saïd-Sadier, Najwane, additional, Lam, Verissa M., additional, Singh, Bhavni, additional, Pettengill, Matthew A., additional, Soares, Fraser, additional, Tattoli, Ivan, additional, Lipinski, Simone, additional, Girardin, Stephen E., additional, Rosenstiel, Philip, additional, and Ojcius, David M., additional

Published
2010
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43. Nod1 and Nod2 direct autophagy by recruiting ATG16L1 to the plasma membrane at the site of bacterial entry

Author

Travassos, Leonardo H, primary, Carneiro, Leticia A M, additional, Ramjeet, Mahendrasingh, additional, Hussey, Seamus, additional, Kim, Yun-Gi, additional, Magalhães, João G, additional, Yuan, Linda, additional, Soares, Fraser, additional, Chea, Evelyn, additional, Le Bourhis, Lionel, additional, Boneca, Ivo G, additional, Allaoui, Abdelmounaaim, additional, Jones, Nicola L, additional, Nuñez, Gabriel, additional, Girardin, Stephen E, additional, and Philpott, Dana J, additional

Published
2009
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45. Shigella Induces Mitochondrial Dysfunction and Cell Death in Nonmyleoid Cells

Author

Carneiro, Leticia A.M., primary, Travassos, Leonardo H., additional, Soares, Fraser, additional, Tattoli, Ivan, additional, Magalhaes, Joao G., additional, Bozza, Marcelo T., additional, Plotkowski, Maria C., additional, Sansonetti, Philippe J., additional, Molkentin, Jeffery D., additional, Philpott, Dana J., additional, and Girardin, Stephen E., additional

Published
2009
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46. NLRX1 does not inhibit MAVS-dependent antiviral signalling.

Author

Soares, Fraser, Tattoli, Ivan, Wortzman, Michael E, Arnoult, Damien, Philpott, Dana J, and Girardin, Stephen E

Subjects
*ANTIVIRAL agents, *CELLULAR signal transduction, *BIOSENSORS, *MOLECULAR biology, *MITOCHONDRIA, *CYTOSOL, *LABORATORY mice
Abstract

NLRX1 is a member of the Nod-like receptor family of intracellular sensors of microbial- and danger-associated molecular patterns. NLRX1 has a N-terminal mitochondrial addressing sequence that localizes the protein to the mitochondrial matrix. Recently, conflicting reports have been presented with regard to the putative implication of NLRX1 as a negative regulator of MAVS-dependent cytosolic antiviral responses. Here, we generated a new NLRX1 knockout mouse strain and observed that bone marrow-derived macrophages and murine embryonic fibroblasts from NLRX1-deficient mice displayed normal antiviral and inflammatory responses following Sendai virus infection. Importantly, wild type and NLRX1-deficient mice exhibited unaltered antiviral and inflammatory gene expression following intranasal challenge with influenza A virus or i.p. injection of Poly (I:C). Together, our results demonstrate that NLRX1 does not participate in the negative regulation of MAVS-dependent antiviral responses. [ABSTRACT FROM AUTHOR]

Published
2013
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47. Nod1 and Nod2 direct autophagy by recruiting ATG16L1 to the plasma membrane at the site of bacterial entry.

Author

Travassos, Leonardo H., Carneiro, Leticia A. M., Ramjeet, Mahendrasingh, Hussey, Seamus, Yun-Gi Kim, Magalhães, João G., Yuan, Linda, Soares, Fraser, Chea, Evelyn, Le Bourhis, Lionel, Boneca, Ivo G., Allaoui, Abdelmounaaim, Jones, Nicola L., Nuñez, Gabriel, Girardin, Stephen E., and Philpott, Dana J.

Subjects
CELL membranes, BACTERIAL diseases, BACTERIA, TRANSCRIPTION factors, CROHN'S disease, PROTEINS
Abstract

Autophagy is emerging as a crucial defense mechanism against bacteria, but the host intracellular sensors responsible for inducing autophagy in response to bacterial infection remain unknown. Here we demonstrated that the intracellular sensors Nod1 and Nod2 are critical for the autophagic response to invasive bacteria. By a mechanism independent of the adaptor RIP2 and transcription factor NF-κB, Nod1 and Nod2 recruited the autophagy protein ATG16L1 to the plasma membrane at the bacterial entry site. In cells homozygous for the Crohn's disease–associated NOD2 frameshift mutation, mutant Nod2 failed to recruit ATG16L1 to the plasma membrane and wrapping of invading bacteria by autophagosomes was impaired. Our results link bacterial sensing by Nod proteins to the induction of autophagy and provide a functional link between Nod2 and ATG16L1, which are encoded by two of the most important genes associated with Crohn's disease. [ABSTRACT FROM AUTHOR]

Published
2010
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