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1. DNMT3A-coordinated splicing governs the stem state switch towards differentiation in embryonic and haematopoietic stem cells

Author

Ramabadran, Raghav, Wang, Jarey H., Reyes, Jaime M., Guzman, Anna G., Gupta, Sinjini, Rosas, Carina, Brunetti, Lorenzo, Gundry, Michael C., Tovy, Ayala, Long, Hali, Gu, Tianpeng, Cullen, Sean M., Tyagi, Siddhartha, Rux, Danielle, Kim, Jean J., Kornblau, Steven M., Kyba, Michael, Stossi, Fabio, Rau, Rachel E., Takahashi, Koichi, Westbrook, Thomas F., and Goodell, Margaret A.

Published
2023
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2. iTAG an optimized IMiD-induced degron for targeted protein degradation in human and murine cells

Author

Bouguenina, Habib, Nicolaou, Stephanos, Le Bihan, Yann-Vaï, Bowling, Elizabeth A., Calderon, Cheyenne, Caldwell, John J., Harrington, Brinley, Hayes, Angela, McAndrew, P. Craig, Mitsopoulos, Costas, Sialana, Fernando Jr., Scarpino, Andrea, Stubbs, Mark, Thapaliya, Arjun, Tyagi, Siddhartha, Wang, Hannah Z., Wood, Francesca, Burke, Rosemary, Raynaud, Florence, Choudhary, Jyoti, van Montfort, Rob L.M., Sadok, Amine, Westbrook, Thomas F., Collins, Ian, and Chopra, Rajesh

Published
2023
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3. iTAG an optimized IMiD-induced degron for targeted protein degradation in human and murine cells

Author

Bouguenina, Habib, primary, Nicolaou, Stephanos, additional, Bihan, Yann-Vaï Le, additional, Bowling, Elizabeth A., additional, Calderon, Cheyenne, additional, Caldwell, John J., additional, Harrington, Brinley, additional, Hayes, Angela, additional, McAndrew, P. Craig, additional, Mitsopoulos, Costas, additional, Sialana, Fernando Jr., additional, Scarpino, Andrea, additional, Stubbs, Mark, additional, Thapaliya, Arjun, additional, Tyagi, Siddhartha, additional, Wang, Hannah Z., additional, Wood, Francesca, additional, Burke, Rosemary, additional, Raynaud, Florence, additional, Choudhary, Jyoti, additional, van Montfort, Rob L.M., additional, Sadok, Amine, additional, Westbrook, Thomas F., additional, Collins, Ian, additional, and Chopra, Rajesh, additional

Published
2024
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4. Modulating Androgen Receptor-Driven Transcription in Prostate Cancer with Selective CDK9 Inhibitors

Author

Richters, André, Doyle, Shelby K., Freeman, David B., Lee, Christina, Leifer, Becky S., Jagannathan, Sajjeev, Kabinger, Florian, Koren, Jošt Vrabič, Struntz, Nicholas B., Urgiles, Julie, Stagg, Ryan A., Curtin, Brice H., Chatterjee, Deep, Mathea, Sebastian, Mikochik, Peter J., Hopkins, Tamara D., Gao, Hua, Branch, Jonathan R., Xin, Hong, Westover, Lori, Bignan, Gilles C., Rupnow, Brent A., Karlin, Kristen L., Olson, Calla M., Westbrook, Thomas F., Vacca, Joseph, Wilfong, Chris M., Trotter, B. Wesley, Saffran, Douglas C., Bischofberger, Norbert, Knapp, Stefan, Russo, Joshua W., Hickson, Ian, Bischoff, James R., Gottardis, Marco M., Balk, Steven P., Lin, Charles Y., Pop, Marius S., and Koehler, Angela N.

Published
2021
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7. Immuno-subtyping of breast cancer reveals distinct myeloid cell profiles and immunotherapy resistance mechanisms

Author

Kim, Ik Sun, Gao, Yang, Welte, Thomas, Wang, Hai, Liu, Jun, Janghorban, Mahnaz, Sheng, Kuanwei, Niu, Yichi, Goldstein, Amit, Zhao, Na, Bado, Igor, Lo, Hin-Ching, Toneff, Michael J., Nguyen, Tuan, Bu, Wen, Jiang, Weiyu, Arnold, James, Gu, Franklin, He, Jian, Jebakumar, Deborah, Walker, Kimberly, Li, Yi, Mo, Qianxing, Westbrook, Thomas F., Zong, Chenghang, Rao, Arundhati, Sreekumar, Arun, Rosen, Jeffrey M., and Zhang, Xiang H.-F.

Published
2019
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9. Combinatorial inhibition of PTPN12-regulated receptors leads to a broadly effective therapeutic strategy in triple-negative breast cancer

Author

Nair, Amritha, Chung, Hsiang-Ching, Sun, Tingting, Tyagi, Siddhartha, Dobrolecki, Lacey E, Dominguez-Vidana, Rocio, Kurley, Sarah J, Orellana, Mayra, Renwick, Alexander, Henke, David M, Katsonis, Panagiotis, Schmitt, Earlene, Chan, Doug W, Li, Hui, Mao, Sufeng, Petrovic, Ivana, Creighton, Chad J, Gutierrez, Carolina, Dubrulle, Julien, Stossi, Fabio, Tyner, Jeffrey W, Lichtarge, Olivier, Lin, Charles Y, Zhang, Bing, Scott, Kenneth L, Hilsenbeck, Susan G, Sun, Jinpeng, Yu, Xiao, Osborne, C Kent, Schiff, Rachel, Christensen, James G, Shields, David J, Rimawi, Mothaffar F, Ellis, Matthew J, Shaw, Chad A, Lewis, Michael T, and Westbrook, Thomas F

Subjects
Cell receptors -- Health aspects, Esterases -- Health aspects, Gene mutation -- Health aspects, Breast cancer -- Genetic aspects -- Development and progression -- Care and treatment, Gene expression -- Health aspects, Biological sciences, Health
Abstract

Author(s): Amritha Nair [1, 2]; Hsiang-Ching Chung [1, 2, 3]; Tingting Sun [1, 2]; Siddhartha Tyagi [1, 2]; Lacey E Dobrolecki [4]; Rocio Dominguez-Vidana [1, 2, 3]; Sarah J Kurley [...]

Published
2018
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12. Figure S2 from ZFTA–RELA Dictates Oncogenic Transcriptional Programs to Drive Aggressive Supratentorial Ependymoma

Author

Arabzade, Amir, primary, Zhao, Yanhua, primary, Varadharajan, Srinidhi, primary, Chen, Hsiao-Chi, primary, Jessa, Selin, primary, Rivas, Bryan, primary, Stuckert, Austin J., primary, Solis, Minerva, primary, Kardian, Alisha, primary, Tlais, Dana, primary, Golbourn, Brian J., primary, Stanton, Ann-Catherine J., primary, Chan, Yuen San, primary, Olson, Calla, primary, Karlin, Kristen L., primary, Kong, Kathleen, primary, Kupp, Robert, primary, Hu, Baoli, primary, Injac, Sarah G., primary, Ngo, Madeline, primary, Wang, Peter R., primary, De León, Luz A., primary, Sahm, Felix, primary, Kawauchi, Daisuke, primary, Pfister, Stefan M., primary, Lin, Charles Y., primary, Hodges, H. Courtney, primary, Singh, Irtisha, primary, Westbrook, Thomas F., primary, Chintagumpala, Murali M., primary, Blaney, Susan M., primary, Parsons, Donald W., primary, Pajtler, Kristian W., primary, Agnihotri, Sameer, primary, Gilbertson, Richard J., primary, Yi, Joanna, primary, Jabado, Nada, primary, Kleinman, Claudia L., primary, Bertrand, Kelsey C., primary, Deneen, Benjamin, primary, and Mack, Stephen C., primary

Published
2023
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13. Table S2 from ZFTA–RELA Dictates Oncogenic Transcriptional Programs to Drive Aggressive Supratentorial Ependymoma

Author

Arabzade, Amir, primary, Zhao, Yanhua, primary, Varadharajan, Srinidhi, primary, Chen, Hsiao-Chi, primary, Jessa, Selin, primary, Rivas, Bryan, primary, Stuckert, Austin J., primary, Solis, Minerva, primary, Kardian, Alisha, primary, Tlais, Dana, primary, Golbourn, Brian J., primary, Stanton, Ann-Catherine J., primary, Chan, Yuen San, primary, Olson, Calla, primary, Karlin, Kristen L., primary, Kong, Kathleen, primary, Kupp, Robert, primary, Hu, Baoli, primary, Injac, Sarah G., primary, Ngo, Madeline, primary, Wang, Peter R., primary, De León, Luz A., primary, Sahm, Felix, primary, Kawauchi, Daisuke, primary, Pfister, Stefan M., primary, Lin, Charles Y., primary, Hodges, H. Courtney, primary, Singh, Irtisha, primary, Westbrook, Thomas F., primary, Chintagumpala, Murali M., primary, Blaney, Susan M., primary, Parsons, Donald W., primary, Pajtler, Kristian W., primary, Agnihotri, Sameer, primary, Gilbertson, Richard J., primary, Yi, Joanna, primary, Jabado, Nada, primary, Kleinman, Claudia L., primary, Bertrand, Kelsey C., primary, Deneen, Benjamin, primary, and Mack, Stephen C., primary

Published
2023
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14. Data from ZFTA–RELA Dictates Oncogenic Transcriptional Programs to Drive Aggressive Supratentorial Ependymoma

Author

Arabzade, Amir, primary, Zhao, Yanhua, primary, Varadharajan, Srinidhi, primary, Chen, Hsiao-Chi, primary, Jessa, Selin, primary, Rivas, Bryan, primary, Stuckert, Austin J., primary, Solis, Minerva, primary, Kardian, Alisha, primary, Tlais, Dana, primary, Golbourn, Brian J., primary, Stanton, Ann-Catherine J., primary, Chan, Yuen San, primary, Olson, Calla, primary, Karlin, Kristen L., primary, Kong, Kathleen, primary, Kupp, Robert, primary, Hu, Baoli, primary, Injac, Sarah G., primary, Ngo, Madeline, primary, Wang, Peter R., primary, De León, Luz A., primary, Sahm, Felix, primary, Kawauchi, Daisuke, primary, Pfister, Stefan M., primary, Lin, Charles Y., primary, Hodges, H. Courtney, primary, Singh, Irtisha, primary, Westbrook, Thomas F., primary, Chintagumpala, Murali M., primary, Blaney, Susan M., primary, Parsons, Donald W., primary, Pajtler, Kristian W., primary, Agnihotri, Sameer, primary, Gilbertson, Richard J., primary, Yi, Joanna, primary, Jabado, Nada, primary, Kleinman, Claudia L., primary, Bertrand, Kelsey C., primary, Deneen, Benjamin, primary, and Mack, Stephen C., primary

Published
2023
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15. Human WDR5 promotes breast cancer growth and metastasis via KMT2-independent translation regulation

Author

Cai, Wesley L, primary, Chen, Jocelyn Fang-Yi, primary, Chen, Huacui, additional, Wingrove, Emily, additional, Kurley, Sarah J, additional, Chan, Lok Hei, additional, Zhang, Meiling, additional, Arnal-Estape, Anna, additional, Zhao, Minghui, additional, Balabaki, Amer, additional, Li, Wenxue, additional, Yu, Xufen, additional, Krop, Ethan D, additional, Dou, Yali, additional, Liu, Yansheng, additional, Jin, Jian, additional, Westbrook, Thomas F, additional, Nguyen, Don X, additional, and Yan, Qin, additional

Published
2022
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16. Author response: Human WDR5 promotes breast cancer growth and metastasis via KMT2-independent translation regulation

Author

Cai, Wesley L, primary, Chen, Jocelyn Fang-Yi, primary, Chen, Huacui, additional, Wingrove, Emily, additional, Kurley, Sarah J, additional, Chan, Lok Hei, additional, Zhang, Meiling, additional, Arnal-Estape, Anna, additional, Zhao, Minghui, additional, Balabaki, Amer, additional, Li, Wenxue, additional, Yu, Xufen, additional, Krop, Ethan D, additional, Dou, Yali, additional, Liu, Yansheng, additional, Jin, Jian, additional, Westbrook, Thomas F, additional, Nguyen, Don X, additional, and Yan, Qin, additional

Published
2022
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18. Modulating Androgen Receptor-Driven Transcription in Prostate Cancer with Selective CDK9 Inhibitors

Author

Richters, André, Doyle, Shelby K., Freeman, David B., Lee, Christina, Leifer, Becky S., Jagannathan, Sajjeev, Kabinger, Florian, Koren, Jošt Vrabič, Struntz, Nicholas B., Urgiles, Julie, Stagg, Ryan A., Curtin, Brice H., Chatterjee, Deep, Mathea, Sebastian, Mikochik, Peter J., Hopkins, Tamara D., Gao, Hua, Branch, Jonathan R., Xin, Hong, Westover, Lori, Bignan, Gilles C., Rupnow, Brent A., Karlin, Kristen L., Olson, Calla M., Westbrook, Thomas F., Vacca, Joseph, Wilfong, Chris M., Trotter, B. Wesley, Saffran, Douglas C., Bischofberger, Norbert, Knapp, Stefan, Russo, Joshua W., Hickson, Ian, Bischoff, James R., Gottardis, Marco M., Balk, Steven P., Lin, Charles Y., Pop, Marius S., Koehler, Angela N., Richters, André, Doyle, Shelby K., Freeman, David B., Lee, Christina, Leifer, Becky S., Jagannathan, Sajjeev, Kabinger, Florian, Koren, Jošt Vrabič, Struntz, Nicholas B., Urgiles, Julie, Stagg, Ryan A., Curtin, Brice H., Chatterjee, Deep, Mathea, Sebastian, Mikochik, Peter J., Hopkins, Tamara D., Gao, Hua, Branch, Jonathan R., Xin, Hong, Westover, Lori, Bignan, Gilles C., Rupnow, Brent A., Karlin, Kristen L., Olson, Calla M., Westbrook, Thomas F., Vacca, Joseph, Wilfong, Chris M., Trotter, B. Wesley, Saffran, Douglas C., Bischofberger, Norbert, Knapp, Stefan, Russo, Joshua W., Hickson, Ian, Bischoff, James R., Gottardis, Marco M., Balk, Steven P., Lin, Charles Y., Pop, Marius S., and Koehler, Angela N.

Abstract

© 2020 The Authors Castration-resistant prostate cancers (CRPCs) lose sensitivity to androgen-deprivation therapies but frequently remain dependent on oncogenic transcription driven by the androgen receptor (AR) and its splice variants. To discover modulators of AR-variant activity, we used a lysate-based small-molecule microarray assay and identified KI-ARv-03 as an AR-variant complex binder that reduces AR-driven transcription and proliferation in prostate cancer cells. We deduced KI-ARv-03 to be a potent, selective inhibitor of CDK9, an important cofactor for AR, MYC, and other oncogenic transcription factors. Further optimization resulted in KB-0742, an orally bioavailable, selective CDK9 inhibitor with potent anti-tumor activity in CRPC models. In 22Rv1 cells, KB-0742 rapidly downregulates nascent transcription, preferentially depleting short half-life transcripts and AR-driven oncogenic programs. In vivo, oral administration of KB-0742 significantly reduced tumor growth in CRPC, supporting CDK9 inhibition as a promising therapeutic strategy to target AR dependence in CRPC. In the pursuit of hormone receptor modulators in prostate cancer, a potent, ultraselective CDK9 inhibitor is discovered. This study describes the most selective inhibitors of CDK9 known to date and provides compelling preclinical in vitro and in vivo support for CDK9 as a therapeutic target.

Published
2022

19. Proteogenomic Landscape of Breast Cancer Tumorigenesis and Targeted Therapy

Author

Krug, Karsten, Jaehnig, Eric J., Satpathy, Shankha, Blumenberg, Lili, Karpova, Alla, Anurag, Meenakshi, Miles, George, Mertins, Philipp, Geffen, Yifat, Tang, Lauren C., Heiman, David I., Cao, Song, Maruvka, Yosef E., Lei, Jonathan T., Huang, Chen, Kothadia, Ramani B., Colaprico, Antonio, Birger, Chet, Wang, Jarey, Dou, Yongchao, Wen, Bo, Shi, Zhiao, Liao, Yuxing, Wiznerowicz, Maciej, Wyczalkowski, Matthew A., Chen, Xi Steven, Kennedy, Jacob J., Paulovich, Amanda G., Thiagarajan, Mathangi, Kinsinger, Christopher R., Hiltke, Tara, Boja, Emily S., Mesri, Mehdi, Robles, Ana I., Rodriguez, Henry, Westbrook, Thomas F., Ding, Li, Getz, Gad, Clauser, Karl R., Fenyö, David, Ruggles, Kelly V., Zhang, Bing, Mani, D.R., Carr, Steven A., Ellis, Matthew J., Gillette, Michael A., Avanessian, Shayan C., Cai, Shuang, Chan, Daniel, Chen, Xian, Edwards, Nathan J., Hoofnagle, Andrew N., Kane, M. Harry, Ketchum, Karen A., Kuhn, Eric, Levine, Douglas A., Li, Shunqiang, Liebler, Daniel C., Liu, Tao, Luo, Jingqin, Madhavan, Subha, Maher, Chris, McDermott, Jason E., McGarvey, Peter B., Oberti, Mauricio, Pandey, Akhilesh, Payne, Samuel H., Ransohoff, David F., Rivers, Robert C., Rodland, Karin D., Rudnick, Paul, Sanders, Melinda E., Shaw, Kenna M., Shih, Ie-Ming, Slebos, Robbert J.C., Smith, Richard D., Snyder, Michael, Stein, Stephen E., Tabb, David L., Thangudu, Ratna R., Thomas, Stefani, Wang, Yue, White, Forest M., Whiteaker, Jeffrey R., Whiteley, Gordon A., Zhang, Hui, Zhang, Zhen, Zhao, Yingming, Zhu, Heng, Zimmerman, Lisa J., Krug, Karsten, Jaehnig, Eric J., Satpathy, Shankha, Blumenberg, Lili, Karpova, Alla, Anurag, Meenakshi, Miles, George, Mertins, Philipp, Geffen, Yifat, Tang, Lauren C., Heiman, David I., Cao, Song, Maruvka, Yosef E., Lei, Jonathan T., Huang, Chen, Kothadia, Ramani B., Colaprico, Antonio, Birger, Chet, Wang, Jarey, Dou, Yongchao, Wen, Bo, Shi, Zhiao, Liao, Yuxing, Wiznerowicz, Maciej, Wyczalkowski, Matthew A., Chen, Xi Steven, Kennedy, Jacob J., Paulovich, Amanda G., Thiagarajan, Mathangi, Kinsinger, Christopher R., Hiltke, Tara, Boja, Emily S., Mesri, Mehdi, Robles, Ana I., Rodriguez, Henry, Westbrook, Thomas F., Ding, Li, Getz, Gad, Clauser, Karl R., Fenyö, David, Ruggles, Kelly V., Zhang, Bing, Mani, D.R., Carr, Steven A., Ellis, Matthew J., Gillette, Michael A., Avanessian, Shayan C., Cai, Shuang, Chan, Daniel, Chen, Xian, Edwards, Nathan J., Hoofnagle, Andrew N., Kane, M. Harry, Ketchum, Karen A., Kuhn, Eric, Levine, Douglas A., Li, Shunqiang, Liebler, Daniel C., Liu, Tao, Luo, Jingqin, Madhavan, Subha, Maher, Chris, McDermott, Jason E., McGarvey, Peter B., Oberti, Mauricio, Pandey, Akhilesh, Payne, Samuel H., Ransohoff, David F., Rivers, Robert C., Rodland, Karin D., Rudnick, Paul, Sanders, Melinda E., Shaw, Kenna M., Shih, Ie-Ming, Slebos, Robbert J.C., Smith, Richard D., Snyder, Michael, Stein, Stephen E., Tabb, David L., Thangudu, Ratna R., Thomas, Stefani, Wang, Yue, White, Forest M., Whiteaker, Jeffrey R., Whiteley, Gordon A., Zhang, Hui, Zhang, Zhen, Zhao, Yingming, Zhu, Heng, and Zimmerman, Lisa J.

Abstract

© 2020 The Authors The integration of mass spectrometry-based proteomics with next-generation DNA and RNA sequencing profiles tumors more comprehensively. Here this “proteogenomics” approach was applied to 122 treatment-naive primary breast cancers accrued to preserve post-translational modifications, including protein phosphorylation and acetylation. Proteogenomics challenged standard breast cancer diagnoses, provided detailed analysis of the ERBB2 amplicon, defined tumor subsets that could benefit from immune checkpoint therapy, and allowed more accurate assessment of Rb status for prediction of CDK4/6 inhibitor responsiveness. Phosphoproteomics profiles uncovered novel associations between tumor suppressor loss and targetable kinases. Acetylproteome analysis highlighted acetylation on key nuclear proteins involved in the DNA damage response and revealed cross-talk between cytoplasmic and mitochondrial acetylation and metabolism. Our results underscore the potential of proteogenomics for clinical investigation of breast cancer through more accurate annotation of targetable pathways and biological features of this remarkably heterogeneous malignancy.

Published
2022

20. The spliceosome is a therapeutic vulnerability in MYC-driven cancer

Author

Hsu, Tiffany Y.-T., Simon, Lukas M., Neill, Nicholas J., Marcotte, Richard, Sayad, Azin, Bland, Christopher S., Echeverria, Gloria V., Sun, Tingting, Kurley, Sarah J., Tyagi, Siddhartha, Karlin, Kristen L., Dominguez-Vidaha, Rocio, Hartman, Jessica D., Renwick, Alexander, Scorsone, Kathleen, Bernardi, Ronald J., Skinner, Samuel O., Jain, Antrix, Orellana, Mayra, Lagisetti, Chandraiah, Golding, Ido, Jung, Sung Y., Neilson, Joel R., Zhang, Xiang H.-F., Cooper, Thomas A., Webb, Thomas R., Neel, Benjamin G., Shaw, Chad A., and Westbrook, Thomas F.

Subjects
Gene therapy -- Methods, Cancer -- Care and treatment, Transcription factors, Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

MYC (also known as c-MYC) overexpression or hyperactivation is one of the most common drivers of human cancer. Despite intensive study, the MYC oncogene remains recalcitrant to therapeutic inhibition. MYC is a transcription factor, and many of its protumorigenic functions have been attributed to its ability to regulate gene expression programs (1-3). Notably, oncogenic MYC activation has also been shown to increase total RNA and protein production in many tissue and disease contexts (4-7). While such increases in RNA and protein production may endow cancer cells with pro-tumour hallmarks, this increase in synthesis may also generate new or heightened burden on MYC-driven cancer cells to process these macromolecules properly (8). Here we discover that the spliceosome is a new target of oncogenic stress in MYC-driven cancers. We identify BUD31 as a MYC-synthetic lethal gene in human mammary epithelial cells, and demonstrate that BUD31 is a component of the core spliceosome required for its assembly and catalytic activity. Core spliceosomal factors (such as SF3B1 and U2AF1) associated with BUD31 are also required to tolerate oncogenic MYC. Notably, MYC hyperactivation induces an increase in total precursor messenger RNA synthesis, suggesting an increased burden on the core spliceosome to process pre-mRNA. In contrast to normal cells, partial inhibition of the spliceosome in MYC-hyperactivated cells leads to global intron retention, widespread defects in pre-mRNA maturation, and deregulation of many essential cell processes. Notably, genetic or pharmacological inhibition of the spliceosome in vivo impairs survival, tumorigenicity and metastatic proclivity of MYC-dependent breast cancers. Collectively, these data suggest that oncogenic MYC confers a collateral stress on splicing, and that components of the spliceosome may be therapeutic entry points for aggressive MYC-driven cancers., To discover genes and cellular processes required to tolerate oncogenic MYC expression, we previously performed a genome-wide MYC-synthetic lethal screen in human mammary epithelial cells (HMECs) engineered with an inducible [...]

Published
2015

21. Correction: A molecular portrait of epithelial–mesenchymal plasticity in prostate cancer associated with clinical outcome

Author

Stylianou, Nataly, Lehman, Melanie L., Wang, Chenwei, Fard, Atefeh Taherian, Rockstroh, Anja, Fazli, Ladan, Jovanovic, Lidija, Ward, Micheal, Sadowski, Martin C., Kashyap, Abhishek S., Buttyan, Ralph, Gleave, Martin E., Westbrook, Thomas F., Williams, Elizabeth D., Gunter, Jennifer H., Nelson, Colleen C., and Hollier, Brett G.

Published
2019
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22. An Animal Model of MYC-Driven Medulloblastoma

Author

Pei, Yanxin, Moore, Colin E., Wang, Jun, Tewari, Alok K., Eroshkin, Alexey, Cho, Yoon-Jae, Witt, Hendrik, Korshunov, Andrey, Read, Tracy-Ann, Sun, Julia L., Schmitt, Earlene M., Miller, C. Ryan, Buckley, Anne F., McLendon, Roger E., Westbrook, Thomas F., Northcott, Paul A., Taylor, Michael D., Pfister, Stefan M., Febbo, Phillip G., and Wechsler-Reya, Robert J.

Published
2012
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23. WDR5 promotes breast cancer growth and metastasis via KMT2-independent translation regulation

Author

Yan, Qin, primary, Chen, Jocelyn Fang-Yi, additional, Cai, Wesley, additional, Chen, Huacui, additional, Wingrove, Emily, additional, Kurley, Sarah, additional, Chan, Lok Hei, additional, Zhang, Meiling, additional, Arnal-Estape, Anna, additional, Zhao, Minghui, additional, Balabaki, Amer, additional, Li, Wenxue, additional, Yu, Xufen, additional, Dou, Yali, additional, Liu, Yansheng, additional, Jin, Jian, additional, Westbrook, Thomas F, additional, and Nguyen, Don, additional

Published
2022
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25. The pINDUCER lentiviral toolkit for inducible RNA interference in vitro and in vivo

Author

Meerbrey, Kristen L., Hu, Guang, Kessler, Jessica D., Roarty, Kevin, Li, Mamie Z., Fang, Justin E., Herschkowitz, Jason I., Burrows, Anna E., Ciccia, Alberto, Sun, Tingting, Schmitt, Earlene M., Bernardi, Ronald J., Fu, Xiaoyong, Bland, Christopher S., Cooper, Thomas A., Schiff, Rachel, Rosen, Jeffrey M., Westbrook, Thomas F., and Elledge, Stephen J.

Published
2011

26. Tumor Suppressor PLK2 May Serve as a Biomarker in Triple-Negative Breast Cancer for Improved Response to PLK1 Therapeutics

Author

Gao, Yang, primary, Kabotyanski, Elena B., additional, Shepherd, Jonathan H., additional, Villegas, Elizabeth, additional, Acosta, Deanna, additional, Hamor, Clark, additional, Sun, Tingting, additional, Montmeyor-Garcia, Celina, additional, He, Xiaping, additional, Dobrolecki, Lacey E., additional, Westbrook, Thomas F., additional, Lewis, Michael T., additional, Hilsenbeck, Susan G., additional, Zhang, Xiang H.-F., additional, Perou, Charles M., additional, and Rosen, Jeffrey M., additional

Published
2021
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27. MYC-driven accumulation of 2-hydroxyglutarate is associated with breast cancer prognosis

Author

Terunuma, Atsushi, Putluri, Nagireddy, Mishra, Prachi, Mathe, Ewy A., Dorsey, Tiffany H., Yi, Ming, Issaq, Haleem J., Zhou, Ming, Killian, J. Keith, Stevenson, Holly S., Karoly, Edward D., Chan, King, Samanta, Susmita, Prieto, DaRue, Hsu, Tiffany Y.T., Kurley, Sarah J., Putluri, Vasanta, Sonavane, Rajni, Edelman, Daniel C., Wulff, Jacob, Starks, Adrienne M., Yang, Yinmeng, Kittles, Rick A., Yfantis, Harry G., Lee, Dong H., Ioffe, Olga B., Schiff, Rachel, Stephens, Robert M., Meltzer, Paul S., Veenstra, Timothy D., Westbrook, Thomas F., Sreekumar, Arun, and Ambs, Stefan

Subjects
Methylation -- Research, Glutamine -- Research -- Health aspects, Breast cancer -- Prognosis -- Research -- Care and treatment -- Development and progression, Health care industry
Abstract

Metabolic profiling of cancer cells has recently been established as a promising tool for the development of therapies and identification of cancer biomarkers. Here we characterized the metabolomic profile of human breast tumors and uncovered intrinsic metabolite signatures in these tumors using an untargeted discovery approach and validation of key metabolites. The oncometabolite 2-hydroxyglutarate (2HG) accumulated at high levels in a subset of tumors and human breast cancer cell lines. We discovered an association between increased 2HG levels and MYC pathway activation in breast cancer, and further corroborated this relationship using MYC overexpression and knockdown in human mammary epithelial and breast cancer cells. Further analyses revealed globally increased DNA methylation in 2HG-high tumors and identified a tumor subtype with high tissue 2HG and a distinct DNA methylation pattern that was associated with poor prognosis and occurred with higher frequency in African-American patients. Tumors of this subtype had a stem cell-like transcriptional signature and tended to overexpress glutaminase, suggestive of a functional relationship between glutamine and 2HG metabolism in breast cancer. Accordingly, 13C-labeled glutamine was incorporated into 2HG in cells with aberrant 2HG accumulation, whereas pharmacologic and siRNA-mediated glutaminase inhibition reduced 2HG levels. Our findings implicate 2HG as a candidate breast cancer oncometabolite associated with MYC activation and poor prognosis., Introduction Gene expression profiling studies of breast cancer led to the discovery of disease subtypes and expression patterns that are predictive of disease outcome (1-3). Recently, metabolomics emerged as a [...]

Published
2014
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28. Inhibition of YTHDF2 triggers proteotoxic cell death in MYC-driven breast cancer

Author

Einstein, Jaclyn M., primary, Perelis, Mark, additional, Chaim, Isaac A., additional, Meena, Jitendra K., additional, Nussbacher, Julia K., additional, Tankka, Alexandra T., additional, Yee, Brian A., additional, Li, Heyuan, additional, Madrigal, Assael A., additional, Neill, Nicholas J., additional, Shankar, Archana, additional, Tyagi, Siddhartha, additional, Westbrook, Thomas F., additional, and Yeo, Gene W., additional

Published
2021
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29. RAS-MAPK-MSK1 pathway modulates ataxin 1 protein levels and toxicity in SCA1

Author

Park, Jeehye, Al-Ramahi, Ismael, Tan, Qiumin, Mollema, Nissa, Diaz-Garcia, Javier R., Gallego-Flores, Tatiana, Lu, Hsiang-Chih, Lagalwar, Sarita, Duvick, Lisa, Kang, Hyojin, Lee, Yoontae, Jafar-Nejad, Paymaan, Sayegh, Layal S., Richman, Ronald, Liu, Xiuyun, Gao, Yan, Shaw, Chad A., Arthur, J. Simon C., Orr, Harry T., Westbrook, Thomas F., Botas, Juan, and Zoghbi, Huda Y.

Subjects
Spinocerebellar ataxia -- Genetic aspects, Cellular control mechanisms -- Research, Cellular proteins -- Properties -- Testing, Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

Many neurodegenerative disorders, such as Alzheimer's, Parkinson's and polyglutamine diseases, share a common pathogenic mechanism: the abnormal accumulation of disease-causing proteins, due to either the mutant protein's resistance to degradation or overexpression of the wild-type protein. We have developed a strategy to identify therapeutic entry points for such neurodegenerative disorders by screening for genetic networks that influence the levels of disease-driving proteins. We applied this approach, which integrates parallel cell-based and Drosophila genetic screens, to spinocerebellar ataxia type 1 (SCA1), a disease caused by expansion of a polyglutamine tract in ataxin 1 (ATXN1). Our approach revealed that downregulation of several components of the RAS-MAPK-MSK1 pathway decreases ATXN1 levels and suppresses neurodegeneration in Drosophila and mice. Importantly, pharmacological inhibitors of components of this pathway also decrease ATXN1 levels, suggesting that these components represent new therapeutic targets in mitigating SCA1. Collectively, these data reveal new therapeutic entry points for SCA1 and provide a proof-of-principle for tackling other classes of intractable neurodegenerative diseases., The increasing prevalence of neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease in the ageing population is one of our most pressing public health issues (1,2). There is no [...]

Published
2013
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30. ZFTA–RELA Dictates Oncogenic Transcriptional Programs to Drive Aggressive Supratentorial Ependymoma

Author

Arabzade, Amir, primary, Zhao, Yanhua, additional, Varadharajan, Srinidhi, additional, Chen, Hsiao-Chi, additional, Jessa, Selin, additional, Rivas, Bryan, additional, Stuckert, Austin J., additional, Solis, Minerva, additional, Kardian, Alisha, additional, Tlais, Dana, additional, Golbourn, Brian J., additional, Stanton, Ann-Catherine J., additional, Chan, Yuen San, additional, Olson, Calla, additional, Karlin, Kristen L., additional, Kong, Kathleen, additional, Kupp, Robert, additional, Hu, Baoli, additional, Injac, Sarah G., additional, Ngo, Madeline, additional, Wang, Peter R., additional, De León, Luz A., additional, Sahm, Felix, additional, Kawauchi, Daisuke, additional, Pfister, Stefan M., additional, Lin, Charles Y., additional, Hodges, H. Courtney, additional, Singh, Irtisha, additional, Westbrook, Thomas F., additional, Chintagumpala, Murali M., additional, Blaney, Susan M., additional, Parsons, Donald W., additional, Pajtler, Kristian W., additional, Agnihotri, Sameer, additional, Gilbertson, Richard J., additional, Yi, Joanna, additional, Jabado, Nada, additional, Kleinman, Claudia L., additional, Bertrand, Kelsey C., additional, Deneen, Benjamin, additional, and Mack, Stephen C., additional

Published
2021
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31. Proteogenomic insights into the biology and treatment of HPV-negative head and neck squamous cell carcinoma

Author

Huang, Chen, primary, Chen, Lijun, additional, Savage, Sara R., additional, Eguez, Rodrigo Vargas, additional, Dou, Yongchao, additional, Li, Yize, additional, da Veiga Leprevost, Felipe, additional, Jaehnig, Eric J., additional, Lei, Jonathan T., additional, Wen, Bo, additional, Schnaubelt, Michael, additional, Krug, Karsten, additional, Song, Xiaoyu, additional, Cieślik, Marcin, additional, Chang, Hui-Yin, additional, Wyczalkowski, Matthew A., additional, Li, Kai, additional, Colaprico, Antonio, additional, Li, Qing Kay, additional, Clark, David J., additional, Hu, Yingwei, additional, Cao, Liwei, additional, Pan, Jianbo, additional, Wang, Yuefan, additional, Cho, Kyung-Cho, additional, Shi, Zhiao, additional, Liao, Yuxing, additional, Jiang, Wen, additional, Anurag, Meenakshi, additional, Ji, Jiayi, additional, Yoo, Seungyeul, additional, Zhou, Daniel Cui, additional, Liang, Wen-Wei, additional, Wendl, Michael, additional, Vats, Pankaj, additional, Carr, Steven A., additional, Mani, D.R., additional, Zhang, Zhen, additional, Qian, Jiang, additional, Chen, Xi S., additional, Pico, Alexander R., additional, Wang, Pei, additional, Chinnaiyan, Arul M., additional, Ketchum, Karen A., additional, Kinsinger, Christopher R., additional, Robles, Ana I., additional, An, Eunkyung, additional, Hiltke, Tara, additional, Mesri, Mehdi, additional, Thiagarajan, Mathangi, additional, Weaver, Alissa M., additional, Sikora, Andrew G., additional, Lubiński, Jan, additional, Wierzbicka, Małgorzata, additional, Wiznerowicz, Maciej, additional, Satpathy, Shankha, additional, Gillette, Michael A., additional, Miles, George, additional, Ellis, Matthew J., additional, Omenn, Gilbert S., additional, Rodriguez, Henry, additional, Boja, Emily S., additional, Dhanasekaran, Saravana M., additional, Ding, Li, additional, Nesvizhskii, Alexey I., additional, El-Naggar, Adel K., additional, Chan, Daniel W., additional, Zhang, Hui, additional, Zhang, Bing, additional, Agarwal, Anupriya, additional, Anderson, Matthew L., additional, Avanessian, Shayan C., additional, Avtonomov, Dmitry, additional, Bathe, Oliver F., additional, Birger, Chet, additional, Birrer, Michael J., additional, Blumenberg, Lili, additional, Bocik, William E., additional, Borate, Uma, additional, Borucki, Melissa, additional, Burke, Meghan C., additional, Cai, Shuang, additional, Calinawan, Anna Pamela, additional, Cerda, Sandra, additional, Charamut, Alyssa, additional, Chen, Lin S., additional, Chowdhury, Shrabanti, additional, Clauser, Karl R., additional, Culpepper, Houston, additional, Czernicki, Tomasz, additional, D'Angelo, Fulvio, additional, Day, Jacob, additional, De Young, Stephanie, additional, Demir, Emek, additional, Ding, Fei, additional, Domagalski, Marcin J., additional, Dort, Joseph C., additional, Druker, Brian, additional, Duffy, Elizabeth, additional, Dyer, Maureen, additional, Edwards, Nathan J., additional, Elburn, Kimberly, additional, Ermakova, Tatiana S., additional, Fenyo, David, additional, Ferrarotto, Renata, additional, Francis, Alicia, additional, Gabriel, Stacey, additional, Garofano, Luciano, additional, Geffen, Yifat, additional, Getz, Gad, additional, Goldthwaite, Charles A., additional, Hannick, Linda I., additional, Hariharan, Pushpa, additional, Hayes, David N., additional, Heiman, David, additional, Hindenach, Barbara, additional, Hoadley, Katherine A., additional, Hostetter, Galen, additional, Hyrcza, Martin, additional, Jewell, Scott D., additional, Jones, Corbin D., additional, Kane, M. Harry, additional, Karz, Alicia, additional, Kothadia, Ramani B., additional, Krek, Azra, additional, Kumar-Sinha, Chandan, additional, Liu, Tao, additional, Liu, Hongwei, additional, Ma, Weiping, additional, Malc, Ewa, additional, Malovannaya, Anna, additional, Mareedu, Sailaja, additional, Markey, Sanford P., additional, Marrero-Oliveras, Annette, additional, Maunganidze, Nicollette, additional, McDermott, Jason E., additional, McGarvey, Peter B., additional, McGee, John, additional, Mieczkowski, Piotr, additional, Migliozzi, Simona, additional, Montgomery, Rebecca, additional, Newton, Chelsea J., additional, Ozbek, Umut, additional, Paulovich, Amanda G., additional, Payne, Samuel H., additional, Pazardzhikliev, Dimitar Dimitrov, additional, Perou, Amy M., additional, Petralia, Francesca, additional, Petrenko, Lyudmila, additional, Piehowski, Paul D., additional, Placantonakis, Dmitris, additional, Polonskaya, Larisa, additional, Ponomareva, Elena V., additional, Potapova, Olga, additional, Qi, Liqun, additional, Qu, Ning, additional, Ramkissoon, Shakti, additional, Reva, Boris, additional, Richey, Shannon, additional, Robinson, Karna, additional, Roche, Nancy, additional, Rodland, Karin, additional, Rohrer, Daniel C., additional, Rykunov, Dmitry, additional, Schadt, Eric E., additional, Shi, Yan, additional, Shutack, Yvonne, additional, Singh, Shilpi, additional, Skelly, Tara, additional, Smith, Richard, additional, Sokoll, Lori J., additional, Stawicki, Jakub, additional, Stein, Stephen E., additional, Suh, James, additional, Szopa, Wojciech, additional, Tabor, Dave, additional, Tan, Donghui, additional, Tansil, Darlene, additional, Teo, Guo Ci, additional, Thangudu, Ratna R., additional, Tognon, Cristina, additional, Traer, Elie, additional, Tsang, Shirley, additional, Tyner, Jeffrey, additional, Um, Ki Sung, additional, Valley, Dana R., additional, Vasilev, Lyubomir Valkov, additional, Vatanian, Negin, additional, Velvulou, Uma, additional, Vernon, Michael, additional, Westbrook, Thomas F., additional, Whiteaker, Jeffrey R., additional, Wu, Yige, additional, Xu, Midie, additional, Yao, Lijun, additional, Yi, Xinpei, additional, Yu, Fengchao, additional, Zaalishvili, Kakhaber, additional, Zakhartsev, Yuriy, additional, Zelt, Robert, additional, Zhao, Grace, additional, and Zhu, Jun, additional

Published
2021
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32. controls oncogenic transformation and neural differentiation through REST degradation

Author

Westbrook, Thomas F., Hu, Guang, Ang, Xiaolu L., Mulligan, Peter, Pavlova, Natalya N., Liang, Anthony, Leng, Yumei, Maehr, Rene, Shi, Yang, Harper, J. Wade, and Elledge, Stephen J.

Subjects
Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

The RE1-silencing transcription factor (REST, also known as NRSF) is a master repressor of neuronal gene expression and neuronal programmes in non-neuronal lineages (1-3). Recently, REST was identified as a [...]

Published
2008

33. Cancer proliferation gene discovery through functional genomics

Author

Schlabach, Michael R., Luo, Ji, Solimini, Nicole L., Hu, Guang, Xu, Qikai, Li, Mamie Z., Zhao, Zhenming, Smogorzewska, Agata, Sowa, Mathew E., Ang, Xiaolu L., Westbrook, Thomas F., Liang, Anthony C., Chang, Kenneth, Hackett, Jennifer A., Harper, J. Wade, Hannon, Gregory J., and Elledge, Stephen J.

Subjects
Genomics -- Research, Cell proliferation -- Genetic aspects, Cancer cells -- Genetic aspects, Cancer cells -- Properties, Cancer -- Research, Cancer -- Diagnosis, Cancer -- Genetic aspects, Oncology, Experimental
Published
2008

34. Spliceosome-targeted therapies trigger an antiviral immune response in triple-negative breast cancer

Author

Bowling, Elizabeth A., primary, Wang, Jarey H., additional, Gong, Fade, additional, Wu, William, additional, Neill, Nicholas J., additional, Kim, Ik Sun, additional, Tyagi, Siddhartha, additional, Orellana, Mayra, additional, Kurley, Sarah J., additional, Dominguez-Vidaña, Rocio, additional, Chung, Hsiang-Ching, additional, Hsu, Tiffany Y.-T., additional, Dubrulle, Julien, additional, Saltzman, Alexander B., additional, Li, Heyuan, additional, Meena, Jitendra K., additional, Canlas, Gino M., additional, Chamakuri, Srinivas, additional, Singh, Swarnima, additional, Simon, Lukas M., additional, Olson, Calla M., additional, Dobrolecki, Lacey E., additional, Lewis, Michael T., additional, Zhang, Bing, additional, Golding, Ido, additional, Rosen, Jeffrey M., additional, Young, Damian W., additional, Malovannaya, Anna, additional, Stossi, Fabio, additional, Miles, George, additional, Ellis, Matthew J., additional, Yu, Lihua, additional, Buonamici, Silvia, additional, Lin, Charles Y., additional, Karlin, Kristen L., additional, Zhang, Xiang H.-F., additional, and Westbrook, Thomas F., additional

Published
2021
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35. A genetic screen for candidate tumor suppressors identifies REST

Author

Westbrook, Thomas F., Yumei Leng, Jean J. Zhao, Mandel, Galil, Chin, Lynda, Martin, Eric S., Schlabach, Michael R., Liang, Anthony C., Bin Feng, Roberts, Thomas M., Hannon, Gregory J., DePinho, Ronald A., and Elledge, Stephen J.

Subjects
Epithelial cells -- Research, Cancer -- Genetic aspects, Cancer -- Research, Biological sciences
Abstract

An RNAi-based genetic screen for genes that suppress transformation of human mammary epithelial cells is reported. The results implicate REST gene as a human tumor suppressor and provide a novel approach to identifying candidate genes that suppress the development of human cancer.

Published
2005

36. Proteogenomic Landscape of Breast Cancer Tumorigenesis and Targeted Therapy

Author

Krug, Karsten, primary, Jaehnig, Eric J., additional, Satpathy, Shankha, additional, Blumenberg, Lili, additional, Karpova, Alla, additional, Anurag, Meenakshi, additional, Miles, George, additional, Mertins, Philipp, additional, Geffen, Yifat, additional, Tang, Lauren C., additional, Heiman, David I., additional, Cao, Song, additional, Maruvka, Yosef E., additional, Lei, Jonathan T., additional, Huang, Chen, additional, Kothadia, Ramani B., additional, Colaprico, Antonio, additional, Birger, Chet, additional, Wang, Jarey, additional, Dou, Yongchao, additional, Wen, Bo, additional, Shi, Zhiao, additional, Liao, Yuxing, additional, Wiznerowicz, Maciej, additional, Wyczalkowski, Matthew A., additional, Chen, Xi Steven, additional, Kennedy, Jacob J., additional, Paulovich, Amanda G., additional, Thiagarajan, Mathangi, additional, Kinsinger, Christopher R., additional, Hiltke, Tara, additional, Boja, Emily S., additional, Mesri, Mehdi, additional, Robles, Ana I., additional, Rodriguez, Henry, additional, Westbrook, Thomas F., additional, Ding, Li, additional, Getz, Gad, additional, Clauser, Karl R., additional, Fenyö, David, additional, Ruggles, Kelly V., additional, Zhang, Bing, additional, Mani, D.R., additional, Carr, Steven A., additional, Ellis, Matthew J., additional, Gillette, Michael A., additional, Avanessian, Shayan C., additional, Cai, Shuang, additional, Chan, Daniel, additional, Chen, Xian, additional, Edwards, Nathan J., additional, Hoofnagle, Andrew N., additional, Kane, M. Harry, additional, Ketchum, Karen A., additional, Kuhn, Eric, additional, Levine, Douglas A., additional, Li, Shunqiang, additional, Liebler, Daniel C., additional, Liu, Tao, additional, Luo, Jingqin, additional, Madhavan, Subha, additional, Maher, Chris, additional, McDermott, Jason E., additional, McGarvey, Peter B., additional, Oberti, Mauricio, additional, Pandey, Akhilesh, additional, Payne, Samuel H., additional, Ransohoff, David F., additional, Rivers, Robert C., additional, Rodland, Karin D., additional, Rudnick, Paul, additional, Sanders, Melinda E., additional, Shaw, Kenna M., additional, Shih, Ie-Ming, additional, Slebos, Robbert J.C., additional, Smith, Richard D., additional, Snyder, Michael, additional, Stein, Stephen E., additional, Tabb, David L., additional, Thangudu, Ratna R., additional, Thomas, Stefani, additional, Wang, Yue, additional, White, Forest M., additional, Whiteaker, Jeffrey R., additional, Whiteley, Gordon A., additional, Zhang, Hui, additional, Zhang, Zhen, additional, Zhao, Yingming, additional, Zhu, Heng, additional, and Zimmerman, Lisa J., additional

Published
2020
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37. A SUMOylation-Dependent Transcriptional Subprogram Is Required for Myc-Driven Tumorigenesis

Author

Kessler, Jessica D., Kahle, Kristopher T., Sun, Tingting, Meerbrey, Kristen L., Schlabach, Michael R., Schmitt, Earlene M., Skinner, Samuel O., Xu, Qikai, Li, Mamie Z., Hartman, Zachary C., Rao, Mitchell, Yu, Peng, Dominguez-Vidana, Rocio, Liang, Anthony C., Solimini, Nicole L., Bernardi, Ronald J., Yu, Bing, Hsu, Tiffany, Golding, Ido, Luo, Ji, Osborne, Kent C., Creighton, Chad J., Hilsenbeck, Susan G., Schiff, Rachel, Shaw, Chad A., Elledge, Stephen J., and Westbrook, Thomas F.

Published
2012
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40. Trisomy of a Down Syndrome Critical Region Globally Amplifies Transcription via HMGN1 Overexpression

Author

Massachusetts Institute of Technology. Department of Biological Engineering, Koch Institute for Integrative Cancer Research at MIT, Kimmerling, Robert John, Manalis, Scott R, Mowery, Cody T., Reyes, Jaime M., Cabal-Hierro, Lucia, Higby, Kelly J., Karlin, Kristen L., Wang, Jarey H., Cejas, Paloma, Lim, Klothilda, Li, Hubo, Furusawa, Takashi, Long, Henry W., Pellman, David, Chapuy, Bjoern, Bustin, Michael, Westbrook, Thomas F., Lin, Charles Y., Lane, Andrew A., Massachusetts Institute of Technology. Department of Biological Engineering, Koch Institute for Integrative Cancer Research at MIT, Kimmerling, Robert John, Manalis, Scott R, Mowery, Cody T., Reyes, Jaime M., Cabal-Hierro, Lucia, Higby, Kelly J., Karlin, Kristen L., Wang, Jarey H., Cejas, Paloma, Lim, Klothilda, Li, Hubo, Furusawa, Takashi, Long, Henry W., Pellman, David, Chapuy, Bjoern, Bustin, Michael, Westbrook, Thomas F., Lin, Charles Y., and Lane, Andrew A.

Abstract

Down syndrome (DS, trisomy 21) is associated with developmental abnormalities and increased leukemia risk. To reconcile chromatin alterations with transcriptome changes, we performed paired exogenous spike-in normalized RNA and chromatin immunoprecipitation sequencing in DS models. Absolute normalization unmasks global amplification of gene expression associated with trisomy 21. Overexpression of the nucleosome binding protein HMGN1 (encoded on chr21q22) recapitulates transcriptional changes seen with triplication of a Down syndrome critical region on distal chromosome 21, and HMGN1 is necessary for B cell phenotypes in DS models. Absolute exogenous-normalized chromatin immunoprecipitation sequencing (ChIP-Rx) also reveals a global increase in histone H3K27 acetylation caused by HMGN1. Transcriptional amplification downstream of HMGN1 is enriched for stage-specific programs of B cells and B cell acute lymphoblastic leukemia, dependent on the developmental cellular context. These data offer a mechanistic explanation for DS transcriptional patterns and suggest that further study of HMGN1 and RNA amplification in diverse DS phenotypes is warranted. How trisomy 21 contributes to Down syndrome phenotypes, including increased leukemia risk, is not well understood. Mowery et al. use per-cell normalization approaches to reveal global transcriptional amplification in Down syndrome models. HMGN1 overexpression is sufficient to induce these alterations and promotes lineage-associated transcriptional programs, signaling, and B cell progenitor phenotypes.

Published
2019

41. Reduction of Global H3K27me3 Enhances HER2/ErbB2 Targeted Therapy

Author

Hirukawa, Alison, primary, Singh, Salendra, additional, Wang, Jarey, additional, Rennhack, Jonathan P., additional, Swiatnicki, Matthew, additional, Sanguin-Gendreau, Virginie, additional, Zuo, Dongmei, additional, Daldoul, Kamilia, additional, Lavoie, Cynthia, additional, Park, Morag, additional, Andrechek, Eran R., additional, Westbrook, Thomas F., additional, Harris, Lyndsay N., additional, Varadan, Vinay, additional, Smith, Harvey W., additional, and Muller, William J., additional

Published
2019
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42. Correction: A molecular portrait of epithelial–mesenchymal plasticity in prostate cancer associated with clinical outcome

Author

Stylianou, Nataly, primary, Lehman, Melanie L., additional, Wang, Chenwei, additional, Fard, Atefeh Taherian, additional, Rockstroh, Anja, additional, Fazli, Ladan, additional, Jovanovic, Lidija, additional, Ward, Micheal, additional, Sadowski, Martin C., additional, Kashyap, Abhishek S., additional, Buttyan, Ralph, additional, Gleave, Martin E., additional, Westbrook, Thomas F., additional, Williams, Elizabeth D., additional, Gunter, Jennifer H., additional, Nelson, Colleen C., additional, and Hollier, Brett G., additional

Published
2018
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43. Trisomy of a Down Syndrome Critical Region Globally Amplifies Transcription via HMGN1 Overexpression

Author

Mowery, Cody T., primary, Reyes, Jaime M., additional, Cabal-Hierro, Lucia, additional, Higby, Kelly J., additional, Karlin, Kristen L., additional, Wang, Jarey H., additional, Kimmerling, Robert J., additional, Cejas, Paloma, additional, Lim, Klothilda, additional, Li, Hubo, additional, Furusawa, Takashi, additional, Long, Henry W., additional, Pellman, David, additional, Chapuy, Bjoern, additional, Bustin, Michael, additional, Manalis, Scott R., additional, Westbrook, Thomas F., additional, Lin, Charles Y., additional, and Lane, Andrew A., additional

Published
2018
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44. Revealing the transcriptional landscape of epithelial-mesenchymal plasticity in mCRPC

Author

Stylianou, Nataly, Lehman, Melanie L., Wang, Chenwei, Jovanovic, Lidija, Rockstroh, Anja, Fard, Atefeh Taherian, Kashyap, Abhishek, Fazli, Ladan, Buttyan, Ralph, Gleave, Martin, Westbrook, Thomas F., Williams, Elizabeth D., Gunter, Jennifer H., Nelson, Colleen C., Hollier, Brett G., Stylianou, Nataly, Lehman, Melanie L., Wang, Chenwei, Jovanovic, Lidija, Rockstroh, Anja, Fard, Atefeh Taherian, Kashyap, Abhishek, Fazli, Ladan, Buttyan, Ralph, Gleave, Martin, Westbrook, Thomas F., Williams, Elizabeth D., Gunter, Jennifer H., Nelson, Colleen C., and Hollier, Brett G.

Abstract

Objective: The epithelial-mesenchymal transition (EMT) is a transient program thought to facilitate cancer metastasis, progression, and treatment resistance. However, the association of EMT with clinical samples has been inconclusive due to the inherent difficulty of tracking such events in-vivo. This study focused on elucidating the transcriptional association of a transient EMT in large patient cohorts. Methods: To investigate a transient epithelial-mesenchymal transition in prostate adenocarcinoma, an inducible and reversible model of SNAI1-mediated EMT was generated. Prostate adenocarcinoma cells that experienced a transient EMT were profiled using the custom made and prostate specific 180k probe microarray. The results were then examined for association in large cancer patient cohorts. Results: Temporal transcriptional profiling of this reversible process revealed the mesenchymal to epithelial reverting transition (MErT) to be enriched in clinical samples of lethal metastatic castration resistant prostate cancer (mCRPC). From this enrichment, a metastasis-derived gene signature was identified to predict more rapid cancer relapse and reduced survival in not only prostate cancer patients but also across a number of other carcinoma types. Additionally, the transcriptional profile of MErT is not a simple mirror image of EMT. The MErT consists of dynamically reversible transcripts as well as transcripts that either remained persistently altered following an EMT or became uniquely activated with MErT. Furthermore, these novel programs were enriched in mCRPC, supporting the role of a reversible EMT in metastasis. Conclusions: This study lays the transcriptional foundation of epithelial-mesenchymal plasticity in prostate cancer progression that supports its involvement and prognostic qualities in this disease.

Published
2018

46. A Druggable Genome Screen Identifies Modifiers of α-Synuclein Levels via a Tiered Cross-Species Validation Approach

Author

Rousseaux, Maxime W.C., primary, Vázquez-Vélez, Gabriel E., additional, Al-Ramahi, Ismael, additional, Jeong, Hyun-Hwan, additional, Bajić, Aleksandar, additional, Revelli, Jean-Pierre, additional, Ye, Hui, additional, Phan, Emily T., additional, Deger, Jennifer M., additional, Perez, Alma M., additional, Kim, Ji-Yoen, additional, Lavery, Laura A., additional, Xu, Qikia, additional, Li, Mamie Z., additional, Kang, Hyojin, additional, Kim, Jean J., additional, Shulman, Joshua M., additional, Westbrook, Thomas F., additional, Elledge, Stephen J., additional, Liu, Zhandong, additional, Botas, Juan, additional, and Zoghbi, Huda Y., additional

Published
2018
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47. A molecular portrait of epithelial–mesenchymal plasticity in prostate cancer associated with clinical outcome

Author

Stylianou, Nataly, primary, Lehman, Melanie L., additional, Wang, Chenwei, additional, Fard, Atefeh Taherian, additional, Rockstroh, Anja, additional, Fazli, Ladan, additional, Jovanovic, Lidija, additional, Ward, Micheal, additional, Sadowski, Martin C., additional, Kashyap, Abhishek S., additional, Buttyan, Ralph, additional, Gleave, Martin E., additional, Westbrook, Thomas F., additional, Williams, Elizabeth D., additional, Gunter, Jennifer H., additional, Nelson, Colleen C., additional, and Hollier, Brett G., additional

Published
2018
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49. Profound Tissue Specificity in Proliferation Control Underlies Cancer Drivers and Aneuploidy Patterns

Author

Sack, Laura Magill, primary, Davoli, Teresa, additional, Li, Mamie Z., additional, Li, Yuyang, additional, Xu, Qikai, additional, Naxerova, Kamila, additional, Wooten, Eric C., additional, Bernardi, Ronald J., additional, Martin, Timothy D., additional, Chen, Ting, additional, Leng, Yumei, additional, Liang, Anthony C., additional, Scorsone, Kathleen A., additional, Westbrook, Thomas F., additional, Wong, Kwok-Kin, additional, and Elledge, Stephen J., additional

Published
2018
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50. A Pan-Cancer Proteogenomic Atlas of PI3K/AKT/mTOR Pathway Alterations

Author

Zhang, Yiqun, primary, Kwok-Shing Ng, Patrick, additional, Kucherlapati, Melanie, additional, Chen, Fengju, additional, Liu, Yuexin, additional, Tsang, Yiu Huen, additional, de Velasco, Guillermo, additional, Jeong, Kang Jin, additional, Akbani, Rehan, additional, Hadjipanayis, Angela, additional, Pantazi, Angeliki, additional, Bristow, Christopher A., additional, Lee, Eunjung, additional, Mahadeshwar, Harshad S., additional, Tang, Jiabin, additional, Zhang, Jianhua, additional, Yang, Lixing, additional, Seth, Sahil, additional, Lee, Semin, additional, Ren, Xiaojia, additional, Song, Xingzhi, additional, Sun, Huandong, additional, Seidman, Jonathan, additional, Luquette, Lovelace J., additional, Xi, Ruibin, additional, Chin, Lynda, additional, Protopopov, Alexei, additional, Westbrook, Thomas F., additional, Shelley, Carl Simon, additional, Choueiri, Toni K., additional, Ittmann, Michael, additional, Van Waes, Carter, additional, Weinstein, John N., additional, Liang, Han, additional, Henske, Elizabeth P., additional, Godwin, Andrew K., additional, Park, Peter J., additional, Kucherlapati, Raju, additional, Scott, Kenneth L., additional, Mills, Gordon B., additional, Kwiatkowski, David J., additional, and Creighton, Chad J., additional

Published
2017
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