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1. Targeting transcription in heart failure via CDK7/12/13 inhibition

Author

Hsu, Austin, Duan, Qiming, Day, Daniel S, Luo, Xin, McMahon, Sarah, Huang, Yu, Feldman, Zachary B, Jiang, Zhen, Zhang, Tinghu, Liang, Yanke, Alexanian, Michael, Padmanabhan, Arun, Brown, Jonathan D, Lin, Charles Y, Gray, Nathanael S, Young, Richard A, Bruneau, Benoit G, and Haldar, Saptarsi M

Subjects
Medical Physiology, Biomedical and Clinical Sciences, Biotechnology, Heart Disease, Genetics, Cardiovascular, 2.1 Biological and endogenous factors, Aetiology, Animals, Cell Line, Tumor, Cyclin-Dependent Kinases, Heart Failure, Humans, Mice, RNA Polymerase II, Stroke Volume
Abstract

Heart failure with reduced ejection fraction (HFrEF) is associated with high mortality, highlighting an urgent need for new therapeutic strategies. As stress-activated cardiac signaling cascades converge on the nucleus to drive maladaptive gene programs, interdicting pathological transcription is a conceptually attractive approach for HFrEF therapy. Here, we demonstrate that CDK7/12/13 are critical regulators of transcription activation in the heart that can be pharmacologically inhibited to improve HFrEF. CDK7/12/13 inhibition using the first-in-class inhibitor THZ1 or RNAi blocks stress-induced transcription and pathologic hypertrophy in cultured rodent cardiomyocytes. THZ1 potently attenuates adverse cardiac remodeling and HFrEF pathogenesis in mice and blocks cardinal features of disease in human iPSC-derived cardiomyocytes. THZ1 suppresses Pol II enrichment at stress-transactivated cardiac genes and inhibits a specific pathologic gene program in the failing mouse heart. These data identify CDK7/12/13 as druggable regulators of cardiac gene transactivation during disease-related stress, suggesting that HFrEF features a critical dependency on transcription that can be therapeutically exploited.

Published
2022

2. CDK7 controls E2F- and MYC-driven proliferative and metabolic vulnerabilities in multiple myeloma

Author

Yao, Yao, Ng, Jessica Fong, Park, Woojun Daniel, Samur, Mehmet, Morelli, Eugenio, Encinas Mayoral, Jessica, Chyra, Zuzana, Xu, Yan, Derebail, Sanika, Epstein, Charles, Nabet, Behnam, Chesi, Marta, Gray, Nathanael S., Young, Richard A., Kwiatkowski, Nicholas, Mitsiades, Constantine, Anderson, Kenneth C., Lin, Charles Y., Munshi, Nikhil C., and Fulciniti, Mariateresa

Published
2023
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3. Dynamic Chromatin Targeting of BRD4 Stimulates Cardiac Fibroblast Activation

Author

Stratton, Matthew S, Bagchi, Rushita A, Felisbino, Marina B, Hirsch, Rachel A, Smith, Harrison E, Riching, Andrew S, Enyart, Blake Y, Koch, Keith A, Cavasin, Maria A, Alexanian, Michael, Song, Kunhua, Qi, Jun, Lemieux, Madeleine E, Srivastava, Deepak, Lam, Maggie PY, Haldar, Saptarsi M, Lin, Charles Y, and McKinsey, Timothy A

Subjects
Biomedical and Clinical Sciences, Cardiovascular Medicine and Haematology, Clinical Sciences, Cardiovascular, Genetics, Heart Disease, Aetiology, 2.1 Biological and endogenous factors, Underpinning research, 1.1 Normal biological development and functioning, Animals, Azepines, Cell Adhesion Molecules, Cells, Cultured, Chromatin, Enhancer Elements, Genetic, Epigenesis, Genetic, Extracellular Matrix, Female, Fibrosis, Heart Failure, Heart Ventricles, Intracellular Signaling Peptides and Proteins, Male, Mice, Mice, Inbred C57BL, Myofibroblasts, Nuclear Proteins, Protein Binding, RNA Polymerase II, Rats, Rats, Sprague-Dawley, Transcription Factors, Transcriptome, Transforming Growth Factor beta, Triazoles, p38 Mitogen-Activated Protein Kinases, chromatin, fibroblast, heart failure, mass spectrometry, phenotype, signaling, Cardiorespiratory Medicine and Haematology, Cardiovascular System & Hematology, Cardiovascular medicine and haematology, Clinical sciences
Abstract

RationaleSmall molecule inhibitors of the acetyl-histone binding protein BRD4 have been shown to block cardiac fibrosis in preclinical models of heart failure (HF). However, since the inhibitors target BRD4 ubiquitously, it is unclear whether this chromatin reader protein functions in cell type-specific manner to control pathological myocardial fibrosis. Furthermore, the molecular mechanisms by which BRD4 stimulates the transcriptional program for cardiac fibrosis remain unknown.ObjectiveWe sought to test the hypothesis that BRD4 functions in a cell-autonomous and signal-responsive manner to control activation of cardiac fibroblasts, which are the major extracellular matrix-producing cells of the heart.Methods and resultsRNA-sequencing, mass spectrometry, and cell-based assays employing primary adult rat ventricular fibroblasts demonstrated that BRD4 functions as an effector of TGF-β (transforming growth factor-β) signaling to stimulate conversion of quiescent cardiac fibroblasts into Periostin (Postn)-positive cells that express high levels of extracellular matrix. These findings were confirmed in vivo through whole-transcriptome analysis of cardiac fibroblasts from mice subjected to transverse aortic constriction and treated with the small molecule BRD4 inhibitor, JQ1. Chromatin immunoprecipitation-sequencing revealed that BRD4 undergoes stimulus-dependent, genome-wide redistribution in cardiac fibroblasts, becoming enriched on a subset of enhancers and super-enhancers, and leading to RNA polymerase II activation and expression of downstream target genes. Employing the Sertad4 (SERTA domain-containing protein 4) locus as a prototype, we demonstrate that dynamic chromatin targeting of BRD4 is controlled, in part, by p38 MAPK (mitogen-activated protein kinase) and provide evidence of a critical function for Sertad4 in TGF-β-mediated cardiac fibroblast activation.ConclusionsThese findings define BRD4 as a central regulator of the pro-fibrotic cardiac fibroblast phenotype, establish a p38-dependent signaling circuit for epigenetic reprogramming in heart failure, and uncover a novel role for Sertad4. The work provides a mechanistic foundation for the development of BRD4 inhibitors as targeted anti-fibrotic therapies for the heart.

Published
2019

4. A C19MC-LIN28A-MYCN Oncogenic Circuit Driven by Hijacked Super-enhancers Is a Distinct Therapeutic Vulnerability in ETMRs: A Lethal Brain Tumor

Author

Sin-Chan, Patrick, Mumal, Iqra, Suwal, Tannu, Ho, Ben, Fan, Xiaolian, Singh, Irtisha, Du, Yuchen, Lu, Mei, Patel, Neilket, Torchia, Jonathon, Popovski, Dean, Fouladi, Maryam, Guilhamon, Paul, Hansford, Jordan R, Leary, Sarah, Hoffman, Lindsey M, Levy, Jean M Mulcahy, Lassaletta, Alvaro, Solano-Paez, Palma, Rivas, Eloy, Reddy, Alyssa, Gillespie, G Yancey, Gupta, Nalin, Van Meter, Timothy E, Nakamura, Hideo, Wong, Tai-Tong, Ra, Young-Shin, Kim, Seung-Ki, Massimi, Luca, Grundy, Richard G, Fangusaro, Jason, Johnston, Donna, Chan, Jennifer, Lafay-Cousin, Lucie, Hwang, Eugene I, Wang, Yin, Catchpoole, Daniel, Michaud, Jean, Ellezam, Benjamin, Ramanujachar, Ramya, Lindsay, Holly, Taylor, Michael D, Hawkins, Cynthia E, Bouffet, Eric, Jabado, Nada, Singh, Sheila K, Kleinman, Claudia L, Barsyte-Lovejoy, Dalia, Li, Xiao-Nan, Dirks, Peter B, Lin, Charles Y, Mack, Stephen C, Rich, Jeremy N, and Huang, Annie

Subjects
Rare Diseases, Neurosciences, Cancer, Genetics, Biotechnology, 5.1 Pharmaceuticals, Development of treatments and therapeutic interventions, Biomarkers, Tumor, Brain Neoplasms, Cell Cycle, Cell Transformation, Neoplastic, Chromosomes, Human, Pair 19, Chromosomes, Human, Pair 2, DNA Copy Number Variations, Enhancer Elements, Genetic, Epigenesis, Genetic, Gene Expression Regulation, Gene Regulatory Networks, Genetic Association Studies, Genetic Predisposition to Disease, Humans, MicroRNAs, Models, Biological, Multigene Family, N-Myc Proto-Oncogene Protein, Neoplasms, Germ Cell and Embryonal, Oncogenes, RNA-Binding Proteins, C19MC, ETMR, LIN28A, MYCN, brain tumor, cell-cycle, epigenetics, microRNA, super-enhancer, therapeutics, Oncology and Carcinogenesis, Oncology & Carcinogenesis
Abstract

Embryonal tumors with multilayered rosettes (ETMRs) are highly lethal infant brain cancers with characteristic amplification of Chr19q13.41 miRNA cluster (C19MC) and enrichment of pluripotency factor LIN28A. Here we investigated C19MC oncogenic mechanisms and discovered a C19MC-LIN28A-MYCN circuit fueled by multiple complex regulatory loops including an MYCN core transcriptional network and super-enhancers resulting from long-range MYCN DNA interactions and C19MC gene fusions. Our data show that this powerful oncogenic circuit, which entraps an early neural lineage network, is potently abrogated by bromodomain inhibitor JQ1, leading to ETMR cell death.

Published
2019

8. 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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9. Targeted brachyury degradation disrupts a highly specific autoregulatory program controlling chordoma cell identity

Author

Sheppard, Hadley E., Dall’Agnese, Alessandra, Park, Woojun D., Shamim, M. Hamza, Dubrulle, Julien, Johnson, Hannah L., Stossi, Fabio, Cogswell, Patricia, Sommer, Josh, Levy, Joan, Sharifnia, Tanaz, Wawer, Mathias J., Nabet, Behnam, Gray, Nathanael S., Clemons, Paul A., Schreiber, Stuart L., Workman, Paul, Young, Richard A., and Lin, Charles Y.

Published
2021
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10. In vivo base editing rescues Hutchinson–Gilford progeria syndrome in mice

Author

Koblan, Luke W., Erdos, Michael R., Wilson, Christopher, Cabral, Wayne A., Levy, Jonathan M., Xiong, Zheng-Mei, Tavarez, Urraca L., Davison, Lindsay M., Gete, Yantenew G., Mao, Xiaojing, Newby, Gregory A., Doherty, Sean P., Narisu, Narisu, Sheng, Quanhu, Krilow, Chad, Lin, Charles Y., Gordon, Leslie B., Cao, Kan, Collins, Francis S., Brown, Jonathan D., and Liu, David R.

Published
2021
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12. Discovery of KB-0742, a Potent, Selective, Orally Bioavailable Small Molecule Inhibitor of CDK9 for MYC-Dependent Cancers

Author

Freeman, David B., primary, Hopkins, Tamara D., additional, Mikochik, Peter J., additional, Vacca, Joseph P., additional, Gao, Hua, additional, Naylor-Olsen, Adel, additional, Rudra, Sonali, additional, Li, Huixu, additional, Pop, Marius S., additional, Villagomez, Rosa A., additional, Lee, Christina, additional, Li, Heng, additional, Zhou, Minyun, additional, Saffran, Douglas C., additional, Rioux, Nathalie, additional, Hood, Tressa R., additional, Day, Melinda A. L., additional, McKeown, Michael R., additional, Lin, Charles Y., additional, Bischofberger, Norbert, additional, and Trotter, B. Wesley, additional

Published
2023
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14. Discovery of a selective inhibitor of doublecortin like kinase 1

Author

Ferguson, Fleur M., Nabet, Behnam, Raghavan, Srivatsan, Liu, Yan, Leggett, Alan L., Kuljanin, Miljan, Kalekar, Radha L., Yang, Annan, He, Shuning, Wang, Jinhua, Ng, Raymond W. S., Sulahian, Rita, Li, Lianbo, Poulin, Emily J., Huang, Ling, Koren, Jost, Dieguez-Martinez, Nora, Espinosa, Sergio, Zeng, Zhiyang, Corona, Cesear R., Vasta, James D., Ohi, Ryoma, Sim, Taebo, Kim, Nam Doo, Harshbarger, Wayne, Lizcano, Jose M., Robers, Matthew B., Muthaswamy, Senthil, Lin, Charles Y., Look, A. Thomas, Haigis, Kevin M., Mancias, Joseph D., Wolpin, Brian M., Aguirre, Andrew J., Hahn, William C., Westover, Kenneth D., and Gray, Nathanael S.

Published
2020
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16. Stabilization of the Max Homodimer with a Small Molecule Attenuates Myc-Driven Transcription

Author

Struntz, Nicholas B., Chen, Andrew, Deutzmann, Anja, Wilson, Robert M., Stefan, Eric, Evans, Helen L., Ramirez, Maricela A., Liang, Tong, Caballero, Francisco, Wildschut, Mattheus H.E., Neel, Dylan V., Freeman, David B., Pop, Marius S., McConkey, Marie, Muller, Sandrine, Curtin, Brice H., Tseng, Hanna, Frombach, Kristen R., Butty, Vincent L., Levine, Stuart S., Feau, Clementine, Elmiligy, Sarah, Hong, Jiyoung A., Lewis, Timothy A., Vetere, Amedeo, Clemons, Paul A., Malstrom, Scott E., Ebert, Benjamin L., Lin, Charles Y., Felsher, Dean W., and Koehler, Angela N.

Published
2019
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17. BET bromodomain proteins regulate enhancer function during adipogenesis

Author

Brown, Jonathan D., Feldman, Zachary B., Doherty, Sean P., Reyes, Jaime M., Rahl, Peter B., Lin, Charles Y., Sheng, Quanhu, Duan, Qiong, Federation, Alexander J., Kung, Andrew L., Haldar, Saptarsi M., Young, Richard A., Plutzky, Jorge, and Bradner, James E.

Published
2018

20. Small-molecule targeting of brachyury transcription factor addiction in chordoma

Author

Sharifnia, Tanaz, Wawer, Mathias J., Chen, Ting, Huang, Qing-Yuan, Weir, Barbara A., Sizemore, Ann, Lawlor, Matthew A., Goodale, Amy, Cowley, Glenn S., Vazquez, Francisca, Ott, Christopher J., Francis, Joshua M., Sassi, Slim, Cogswell, Patricia, Sheppard, Hadley E., Zhang, Tinghu, Gray, Nathanael S., Clarke, Paul A., Blagg, Julian, Workman, Paul, Sommer, Josh, Hornicek, Francis, Root, David E., Hahn, William C., Bradner, James E., Wong, Kwok K., Clemons, Paul A., Lin, Charles Y., Kotz, Joanne D., and Schreiber, Stuart L.

Published
2019
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22. Supplementary Table from Transcriptional Plasticity Drives Leukemia Immune Escape

Author

Eagle, Kenneth, primary, Harada, Taku, primary, Kalfon, Jérémie, primary, Perez, Monika W., primary, Heshmati, Yaser, primary, Ewers, Jazmin, primary, Koren, Jošt Vrabič, primary, Dempster, Joshua M., primary, Kugener, Guillaume, primary, Paralkar, Vikram R., primary, Lin, Charles Y., primary, Dharia, Neekesh V., primary, Stegmaier, Kimberly, primary, Orkin, Stuart H., primary, and Pimkin, Maxim, primary

Published
2023
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23. Supplementary Figure from Transcriptional Plasticity Drives Leukemia Immune Escape

Author

Eagle, Kenneth, primary, Harada, Taku, primary, Kalfon, Jérémie, primary, Perez, Monika W., primary, Heshmati, Yaser, primary, Ewers, Jazmin, primary, Koren, Jošt Vrabič, primary, Dempster, Joshua M., primary, Kugener, Guillaume, primary, Paralkar, Vikram R., primary, Lin, Charles Y., primary, Dharia, Neekesh V., primary, Stegmaier, Kimberly, primary, Orkin, Stuart H., primary, and Pimkin, Maxim, primary

Published
2023
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24. Supplementary Data from Transcriptional Plasticity Drives Leukemia Immune Escape

Author

Eagle, Kenneth, primary, Harada, Taku, primary, Kalfon, Jérémie, primary, Perez, Monika W., primary, Heshmati, Yaser, primary, Ewers, Jazmin, primary, Koren, Jošt Vrabič, primary, Dempster, Joshua M., primary, Kugener, Guillaume, primary, Paralkar, Vikram R., primary, Lin, Charles Y., primary, Dharia, Neekesh V., primary, Stegmaier, Kimberly, primary, Orkin, Stuart H., primary, and Pimkin, Maxim, primary

Published
2023
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25. Data from Transcriptional Plasticity Drives Leukemia Immune Escape

Author

Eagle, Kenneth, primary, Harada, Taku, primary, Kalfon, Jérémie, primary, Perez, Monika W., primary, Heshmati, Yaser, primary, Ewers, Jazmin, primary, Koren, Jošt Vrabič, primary, Dempster, Joshua M., primary, Kugener, Guillaume, primary, Paralkar, Vikram R., primary, Lin, Charles Y., primary, Dharia, Neekesh V., primary, Stegmaier, Kimberly, primary, Orkin, Stuart H., primary, and Pimkin, Maxim, primary

Published
2023
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26. 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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27. 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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28. 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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29. Data from Oncogenic Deregulation of EZH2 as an Opportunity for Targeted Therapy in Lung Cancer

Author

Zhang, Haikuo, primary, Qi, Jun, primary, Reyes, Jaime M., primary, Li, Lewyn, primary, Rao, Prakash K., primary, Li, Fugen, primary, Lin, Charles Y., primary, Perry, Jennifer A., primary, Lawlor, Matthew A., primary, Federation, Alexander, primary, De Raedt, Thomas, primary, Li, Yvonne Y., primary, Liu, Yan, primary, Duarte, Melissa A., primary, Zhang, Yanxi, primary, Herter-Sprie, Grit S., primary, Kikuchi, Eiki, primary, Carretero, Julian, primary, Perou, Charles M., primary, Reibel, Jacob B., primary, Paulk, Joshiawa, primary, Bronson, Roderick T., primary, Watanabe, Hideo, primary, Brainson, Christine Fillmore, primary, Kim, Carla F., primary, Hammerman, Peter S., primary, Brown, Myles, primary, Cichowski, Karen, primary, Long, Henry, primary, Bradner, James E., primary, and Wong, Kwok-Kin, primary

Published
2023
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30. Supplementary Figures S1 - S5, Tables S1 - S2 from Oncogenic Deregulation of EZH2 as an Opportunity for Targeted Therapy in Lung Cancer

Author

Zhang, Haikuo, primary, Qi, Jun, primary, Reyes, Jaime M., primary, Li, Lewyn, primary, Rao, Prakash K., primary, Li, Fugen, primary, Lin, Charles Y., primary, Perry, Jennifer A., primary, Lawlor, Matthew A., primary, Federation, Alexander, primary, De Raedt, Thomas, primary, Li, Yvonne Y., primary, Liu, Yan, primary, Duarte, Melissa A., primary, Zhang, Yanxi, primary, Herter-Sprie, Grit S., primary, Kikuchi, Eiki, primary, Carretero, Julian, primary, Perou, Charles M., primary, Reibel, Jacob B., primary, Paulk, Joshiawa, primary, Bronson, Roderick T., primary, Watanabe, Hideo, primary, Brainson, Christine Fillmore, primary, Kim, Carla F., primary, Hammerman, Peter S., primary, Brown, Myles, primary, Cichowski, Karen, primary, Long, Henry, primary, Bradner, James E., primary, and Wong, Kwok-Kin, primary

Published
2023
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31. Supplementary Table 3 from Oncogenic Deregulation of EZH2 as an Opportunity for Targeted Therapy in Lung Cancer

Author

Zhang, Haikuo, primary, Qi, Jun, primary, Reyes, Jaime M., primary, Li, Lewyn, primary, Rao, Prakash K., primary, Li, Fugen, primary, Lin, Charles Y., primary, Perry, Jennifer A., primary, Lawlor, Matthew A., primary, Federation, Alexander, primary, De Raedt, Thomas, primary, Li, Yvonne Y., primary, Liu, Yan, primary, Duarte, Melissa A., primary, Zhang, Yanxi, primary, Herter-Sprie, Grit S., primary, Kikuchi, Eiki, primary, Carretero, Julian, primary, Perou, Charles M., primary, Reibel, Jacob B., primary, Paulk, Joshiawa, primary, Bronson, Roderick T., primary, Watanabe, Hideo, primary, Brainson, Christine Fillmore, primary, Kim, Carla F., primary, Hammerman, Peter S., primary, Brown, Myles, primary, Cichowski, Karen, primary, Long, Henry, primary, Bradner, James E., primary, and Wong, Kwok-Kin, primary

Published
2023
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32. Supplementary Methods from Oncogenic Deregulation of EZH2 as an Opportunity for Targeted Therapy in Lung Cancer

Author

Zhang, Haikuo, primary, Qi, Jun, primary, Reyes, Jaime M., primary, Li, Lewyn, primary, Rao, Prakash K., primary, Li, Fugen, primary, Lin, Charles Y., primary, Perry, Jennifer A., primary, Lawlor, Matthew A., primary, Federation, Alexander, primary, De Raedt, Thomas, primary, Li, Yvonne Y., primary, Liu, Yan, primary, Duarte, Melissa A., primary, Zhang, Yanxi, primary, Herter-Sprie, Grit S., primary, Kikuchi, Eiki, primary, Carretero, Julian, primary, Perou, Charles M., primary, Reibel, Jacob B., primary, Paulk, Joshiawa, primary, Bronson, Roderick T., primary, Watanabe, Hideo, primary, Brainson, Christine Fillmore, primary, Kim, Carla F., primary, Hammerman, Peter S., primary, Brown, Myles, primary, Cichowski, Karen, primary, Long, Henry, primary, Bradner, James E., primary, and Wong, Kwok-Kin, primary

Published
2023
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33. Abstract 15707: Histone Deacetylase Inhibition Reverses Preexisting Diastolic Dysfunction and Blocks Covert Extracellular Matrix Remodeling

Author

Travers, Joshua G, Wennersten, Sara A, Pena, Brisa, Bagchi, Rushita A, Smith, Harrison E, Hirsch, Rachel A, Vanderlinden, Lauren A, Lin, Ying-Hsi, Dobrinskikh, Evgenia, Demos-Davies, Kimberly M, Cavasin, Maria A, Mestroni, Luisa, Steinkuhler, Christian, Houser, Steven R, Lin, Charles Y, Lam, Maggie P, and McKinsey, Timothy A

Published
2020
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35. IRF2 is a master regulator of human keratinocyte stem cell fate

Author

Mercado, Nicolas, Schutzius, Gabi, Kolter, Christian, Estoppey, David, Bergling, Sebastian, Roma, Guglielmo, Gubser Keller, Caroline, Nigsch, Florian, Salathe, Adrian, Terranova, Remi, Reece-Hoyes, John, Alford, John, Russ, Carsten, Knehr, Judith, Hoepfner, Dominic, Aebi, Alexandra, Ruffner, Heinz, Beck, Tanner C., Jagannathan, Sajjeev, Olson, Calla M., Sheppard, Hadley E., Elsarrag, Selma Z., Bouwmeester, Tewis, Frederiksen, Mathias, Lohmann, Felix, Lin, Charles Y., and Kirkland, Susan

Published
2019
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36. 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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40. Cellular Maturation of Oligodendrocytes is Governed by Transient Gene Melting

Author

Allan, Kevin C., primary, Miller, Tyler E., additional, Morton, Andrew R., additional, Scavuzzo, Marissa A., additional, Elitt, Matthew S., additional, Clayton, Benjamin L.L., additional, Hu, Lucille R., additional, Vrabic, Jost K., additional, Olsen, Hannah E., additional, Factor, Daniel C., additional, Henninger, Jonathan E., additional, Young, Richard A., additional, Lin, Charles Y., additional, Scacheri, Peter C., additional, and Tesar, Paul J., additional

Published
2022
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41. CDK7 Inhibition Targets Proliferative and Metabolic Oncogenic Vulnerabilities in Multiple Myeloma

Author

Yao, Yao, primary, Fong Ng, Jessica, additional, Park, Woojun D, additional, Samur, Mehmet K., additional, Morelli, Eugenio, additional, Kwiatkowski, Nicholas P, additional, Encinas Mayoral, Jessica, additional, Chyra, Zuzana, additional, Xu, Yan, additional, Nabet, Behnam, additional, Chesi, Marta, additional, Gray, Nathaniel, additional, Young, Richard A., additional, Anderson, Kenneth C., additional, Lin, Charles Y, additional, Munshi, Nikhil C, additional, and Fulciniti, Mariateresa, additional

Published
2022
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43. Active medulloblastoma enhancers reveal subgroup-specific cellular origins

Author

Lin, Charles Y., Erkek, Serap, Tong, Yiai, Yin, Linlin, Federation, Alexander J., Zapatka, Marc, Haldipur, Parthiv, Kawauchi, Daisuke, Risch, Thomas, Warnatz, Hans-Jörg, Worst, Barbara C., Ju, Bensheng, Orr, Brent A., Zeid, Rhamy, Polaski, Donald R., Segura-Wang, Maia, Waszak, Sebastian M., Jones, David T. W., Kool, Marcel, Hovestadt, Volker, Buchhalter, Ivo, Sieber, Laura, Johann, Pascal, Chavez, Lukas, Gröschel, Stefan, Ryzhova, Marina, Korshunov, Andrey, Chen, Wenbiao, Chizhikov, Victor V., Millen, Kathleen J., Amstislavskiy, Vyacheslav, Lehrach, Hans, Yaspo, Marie-Laure, Eils, Roland, Lichter, Peter, Korbel, Jan O., Pfister, Stefan M., Bradner, James E., and Northcott, Paul A.

Published
2016
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45. Abstract 6355: A characterisation of direct and indirect transcription factor inhibition to target brachyury in chordoma

Author

Sheppard, Hadley E., primary, Dall’Agnese, Alessandra, additional, Park, Woojun D., additional, Shamim, M. Shamim, additional, Dubrulle, Julien, additional, Johnson, Hannah L., additional, Stossi, Fabio, additional, Sommer, Josh, additional, Levy, Joan, additional, Sharifnia, Tanaz, additional, Wawer, Mathias, additional, Nabet, Behnam, additional, Clemons, Paul A., additional, Schreiber, Stuart L., additional, Clarke, Paul, additional, Young, Rick, additional, Lin, Charles Y., additional, and Workman, Paul, additional

Published
2022
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47. Transcriptional Plasticity Drives Leukemia Immune Escape

Author

Eagle, Kenneth, primary, Harada, Taku, additional, Kalfon, Jérémie, additional, Perez, Monika W., additional, Heshmati, Yaser, additional, Ewers, Jazmin, additional, Koren, Jošt Vrabič, additional, Dempster, Joshua M., additional, Kugener, Guillaume, additional, Paralkar, Vikram R., additional, Lin, Charles Y., additional, Dharia, Neekesh V., additional, Stegmaier, Kimberly, additional, Orkin, Stuart H., additional, and Pimkin, Maxim, additional

Published
2022
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49. An oncogenic enhancer encodes selective selenium dependency in AML

Author

Eagle, Kenneth, primary, Jiang, Yajian, additional, Shi, Xiangguo, additional, Li, Minhua, additional, Obholzer, Nikolaus D., additional, Hu, Tianyuan, additional, Perez, Monika W., additional, Koren, Jošt Vrabič, additional, Kitano, Ayumi, additional, Yi, Joanna S., additional, Lin, Charles Y., additional, and Nakada, Daisuke, additional

Published
2022
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50. Impact of sarcopenia and myosteatosis on survival outcomes for patients with head and neck cancer undergoing curative-intent treatment.

Author

Ahern, Elizabeth, Brown, Teresa Ellen, Campbell, Louise, Hughes, Brett G. M., Banks, Merrilyn, Lin, Charles Y., Kenny, Lizbeth M., and Bauer, Judith

Subjects
SKELETAL muscle physiology, HEAD & neck cancer treatment, CANCER patient psychology, BODY composition, CONFIDENCE intervals, CROSS-sectional method, SARCOPENIA, HEAD & neck cancer, TREATMENT effectiveness, CHEMORADIOTHERAPY, COMPARATIVE studies, MALNUTRITION, SURVIVAL analysis (Biometry), DESCRIPTIVE statistics, COMPUTED tomography, LUMBAR vertebrae, ODDS ratio, SQUAMOUS cell carcinoma, OVERALL survival, DISEASE complications, EVALUATION
Abstract

Malnutrition and sarcopenia are prevalent in patients with head and neck squamous cell carcinoma (HNSCC). Pre-treatment sarcopenia and adverse oncological outcomes in this population are well described. The impact of myosteatosis and post-treatment sarcopenia is less well known. Patients with HNSCC (n = 125) undergoing chemoradiotherapy, radiotherapy alone and/or surgery were assessed for sarcopenia and myosteatosis, using cross-sectional computed tomography (CT) imaging at the third lumbar (L3) vertebra, at baseline and 3 months post-treatment. Outcomes were overall survival (OS) at 12 months and 5 years post-treatment. One hundred and one participants had a CT scan evaluable at one or two time points, of which sixty-seven (66 %) participants were sarcopenic on at least one time point. Reduced muscle attenuation affected 93 % (n = 92) pre-treatment compared with 97 % (n = 90) post-treatment. Five-year OS favoured those without post-treatment sarcopenia (hazard ratio, HR 0·37, 95 % CI 0·16, 0·88, P = 0·06) and those without both post-treatment myosteatosis and sarcopenia (HR 0·33, 95 % CI 0·13, 0·83, P = 0·06). Overall, rates of myosteatosis were high at both pre- and post-treatment time points. Post-treatment sarcopenia was associated with worse 5-year OS, as was post-treatment sarcopenia in those who had myosteatosis. Post-treatment sarcopenia should be evaluated as an independent risk factor for decreased long-term survival post-treatment containing radiotherapy (RT) for HNSCC. [ABSTRACT FROM AUTHOR]

Published
2023
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