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2. SHP2 blockade enhances anti-tumor immunity via tumor cell intrinsic and extrinsic mechanisms

Author

Wang, Ye, Mohseni, Morvarid, Grauel, Angelo, Diez, Javier Estrada, Guan, Wei, Liang, Simon, Choi, Jiyoung Elizabeth, Pu, Minying, Chen, Dongshu, Laszewski, Tyler, Schwartz, Stephanie, Gu, Jane, Mansur, Leandra, Burks, Tyler, Brodeur, Lauren, Velazquez, Roberto, Kovats, Steve, Pant, Bhavesh, Buruzula, Giri, Deng, Emily, Chen, Julie T., Sari-Sarraf, Farid, Dornelas, Christina, Varadarajan, Malini, Yu, Haiyan, Liu, Chen, Lim, Joanne, Hao, Huai-Xiang, Jiang, Xiaomo, Malamas, Anthony, LaMarche, Matthew J., Geyer, Felipe Correa, McLaughlin, Margaret, Costa, Carlotta, Wagner, Joel, Ruddy, David, Jayaraman, Pushpa, Kirkpatrick, Nathaniel D., Zhang, Pu, Iartchouk, Oleg, Aardalen, Kimberly, Cremasco, Viviana, Dranoff, Glenn, Engelman, Jeffrey A., Silver, Serena, Wang, Hongyun, Hastings, William D., and Goldoni, Silvia

Published
2021
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4. Supplementary Data from Development of Anti-CD32b Antibodies with Enhanced Fc Function for the Treatment of B and Plasma Cell Malignancies

Author

Lu, Haihui, primary, Molony, Ryan D., primary, Chen, Dongshu, primary, Jang, Sunyoung, primary, Wolf, Babette, primary, Ewert, Stefan, primary, Flaherty, Meghan, primary, Xu, Fangmin, primary, Isim, Sinan, primary, Shim, Yeonju, primary, Dornelas, Christina, primary, Balke, Nicole, primary, Leber, Xavier Charles, primary, Scharenberg, Meike, primary, Koelln, Johanna, primary, Choi, Eugene, primary, Ward, Rebecca, primary, Johnson, Jennifer, primary, Calzascia, Thomas, primary, Isnardi, Isabelle, primary, Williams, Juliet A., primary, Lindenbergh, Pieter L., primary, van de Donk, Niels W.C.J., primary, Mutis, Tuna, primary, Huet, Heather, primary, Lees, Emma, primary, and Meyer, Matthew J., primary

Published
2023
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5. Supplementary Figures from Development of Anti-CD32b Antibodies with Enhanced Fc Function for the Treatment of B and Plasma Cell Malignancies

Author

Lu, Haihui, primary, Molony, Ryan D., primary, Chen, Dongshu, primary, Jang, Sunyoung, primary, Wolf, Babette, primary, Ewert, Stefan, primary, Flaherty, Meghan, primary, Xu, Fangmin, primary, Isim, Sinan, primary, Shim, Yeonju, primary, Dornelas, Christina, primary, Balke, Nicole, primary, Leber, Xavier Charles, primary, Scharenberg, Meike, primary, Koelln, Johanna, primary, Choi, Eugene, primary, Ward, Rebecca, primary, Johnson, Jennifer, primary, Calzascia, Thomas, primary, Isnardi, Isabelle, primary, Williams, Juliet A., primary, Lindenbergh, Pieter L., primary, van de Donk, Niels W.C.J., primary, Mutis, Tuna, primary, Huet, Heather, primary, Lees, Emma, primary, and Meyer, Matthew J., primary

Published
2023
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6. Supplementary Figures from Inhibition of Casein Kinase 1 Alpha Prevents Acquired Drug Resistance to Erlotinib in EGFR-Mutant Non–Small Cell Lung Cancer

Author

Lantermann, Alexandra B., primary, Chen, Dongshu, primary, McCutcheon, Kaitlin, primary, Hoffman, Greg, primary, Frias, Elizabeth, primary, Ruddy, David, primary, Rakiec, Daniel, primary, Korn, Joshua, primary, McAllister, Gregory, primary, Stegmeier, Frank, primary, Meyer, Matthew J., primary, and Sharma, Sreenath V., primary

Published
2023
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7. Data from Inhibition of Casein Kinase 1 Alpha Prevents Acquired Drug Resistance to Erlotinib in EGFR-Mutant Non–Small Cell Lung Cancer

Author

Lantermann, Alexandra B., primary, Chen, Dongshu, primary, McCutcheon, Kaitlin, primary, Hoffman, Greg, primary, Frias, Elizabeth, primary, Ruddy, David, primary, Rakiec, Daniel, primary, Korn, Joshua, primary, McAllister, Gregory, primary, Stegmeier, Frank, primary, Meyer, Matthew J., primary, and Sharma, Sreenath V., primary

Published
2023
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9. Supplementary Figure 3 from An Antibody That Locks HER3 in the Inactive Conformation Inhibits Tumor Growth Driven by HER2 or Neuregulin

Author

Garner, Andrew P., primary, Bialucha, Carl U., primary, Sprague, Elizabeth R., primary, Garrett, Joan T., primary, Sheng, Qing, primary, Li, Sharon, primary, Sineshchekova, Olga, primary, Saxena, Parmita, primary, Sutton, Cammie R., primary, Chen, Dongshu, primary, Chen, Yan, primary, Wang, Huiqin, primary, Liang, Jinsheng, primary, Das, Rita, primary, Mosher, Rebecca, primary, Gu, Jian, primary, Huang, Alan, primary, Haubst, Nicole, primary, Zehetmeier, Carolin, primary, Haberl, Manuela, primary, Elis, Winfried, primary, Kunz, Christian, primary, Heidt, Analeah B., primary, Herlihy, Kara, primary, Murtie, Joshua, primary, Schuller, Alwin, primary, Arteaga, Carlos L., primary, Sellers, William R., primary, and Ettenberg, Seth A., primary

Published
2023
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10. Data from An Antibody That Locks HER3 in the Inactive Conformation Inhibits Tumor Growth Driven by HER2 or Neuregulin

Author

Garner, Andrew P., primary, Bialucha, Carl U., primary, Sprague, Elizabeth R., primary, Garrett, Joan T., primary, Sheng, Qing, primary, Li, Sharon, primary, Sineshchekova, Olga, primary, Saxena, Parmita, primary, Sutton, Cammie R., primary, Chen, Dongshu, primary, Chen, Yan, primary, Wang, Huiqin, primary, Liang, Jinsheng, primary, Das, Rita, primary, Mosher, Rebecca, primary, Gu, Jian, primary, Huang, Alan, primary, Haubst, Nicole, primary, Zehetmeier, Carolin, primary, Haberl, Manuela, primary, Elis, Winfried, primary, Kunz, Christian, primary, Heidt, Analeah B., primary, Herlihy, Kara, primary, Murtie, Joshua, primary, Schuller, Alwin, primary, Arteaga, Carlos L., primary, Sellers, William R., primary, and Ettenberg, Seth A., primary

Published
2023
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13. Supplementary Figure 6 from An Antibody That Locks HER3 in the Inactive Conformation Inhibits Tumor Growth Driven by HER2 or Neuregulin

Author

Garner, Andrew P., primary, Bialucha, Carl U., primary, Sprague, Elizabeth R., primary, Garrett, Joan T., primary, Sheng, Qing, primary, Li, Sharon, primary, Sineshchekova, Olga, primary, Saxena, Parmita, primary, Sutton, Cammie R., primary, Chen, Dongshu, primary, Chen, Yan, primary, Wang, Huiqin, primary, Liang, Jinsheng, primary, Das, Rita, primary, Mosher, Rebecca, primary, Gu, Jian, primary, Huang, Alan, primary, Haubst, Nicole, primary, Zehetmeier, Carolin, primary, Haberl, Manuela, primary, Elis, Winfried, primary, Kunz, Christian, primary, Heidt, Analeah B., primary, Herlihy, Kara, primary, Murtie, Joshua, primary, Schuller, Alwin, primary, Arteaga, Carlos L., primary, Sellers, William R., primary, and Ettenberg, Seth A., primary

Published
2023
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14. Supplementary Figure 4 from An Antibody That Locks HER3 in the Inactive Conformation Inhibits Tumor Growth Driven by HER2 or Neuregulin

Author

Garner, Andrew P., primary, Bialucha, Carl U., primary, Sprague, Elizabeth R., primary, Garrett, Joan T., primary, Sheng, Qing, primary, Li, Sharon, primary, Sineshchekova, Olga, primary, Saxena, Parmita, primary, Sutton, Cammie R., primary, Chen, Dongshu, primary, Chen, Yan, primary, Wang, Huiqin, primary, Liang, Jinsheng, primary, Das, Rita, primary, Mosher, Rebecca, primary, Gu, Jian, primary, Huang, Alan, primary, Haubst, Nicole, primary, Zehetmeier, Carolin, primary, Haberl, Manuela, primary, Elis, Winfried, primary, Kunz, Christian, primary, Heidt, Analeah B., primary, Herlihy, Kara, primary, Murtie, Joshua, primary, Schuller, Alwin, primary, Arteaga, Carlos L., primary, Sellers, William R., primary, and Ettenberg, Seth A., primary

Published
2023
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15. Supplementary Figure Legend from An Antibody That Locks HER3 in the Inactive Conformation Inhibits Tumor Growth Driven by HER2 or Neuregulin

Author

Garner, Andrew P., primary, Bialucha, Carl U., primary, Sprague, Elizabeth R., primary, Garrett, Joan T., primary, Sheng, Qing, primary, Li, Sharon, primary, Sineshchekova, Olga, primary, Saxena, Parmita, primary, Sutton, Cammie R., primary, Chen, Dongshu, primary, Chen, Yan, primary, Wang, Huiqin, primary, Liang, Jinsheng, primary, Das, Rita, primary, Mosher, Rebecca, primary, Gu, Jian, primary, Huang, Alan, primary, Haubst, Nicole, primary, Zehetmeier, Carolin, primary, Haberl, Manuela, primary, Elis, Winfried, primary, Kunz, Christian, primary, Heidt, Analeah B., primary, Herlihy, Kara, primary, Murtie, Joshua, primary, Schuller, Alwin, primary, Arteaga, Carlos L., primary, Sellers, William R., primary, and Ettenberg, Seth A., primary

Published
2023
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16. Supplementary Figure 5 from An Antibody That Locks HER3 in the Inactive Conformation Inhibits Tumor Growth Driven by HER2 or Neuregulin

Author

Garner, Andrew P., primary, Bialucha, Carl U., primary, Sprague, Elizabeth R., primary, Garrett, Joan T., primary, Sheng, Qing, primary, Li, Sharon, primary, Sineshchekova, Olga, primary, Saxena, Parmita, primary, Sutton, Cammie R., primary, Chen, Dongshu, primary, Chen, Yan, primary, Wang, Huiqin, primary, Liang, Jinsheng, primary, Das, Rita, primary, Mosher, Rebecca, primary, Gu, Jian, primary, Huang, Alan, primary, Haubst, Nicole, primary, Zehetmeier, Carolin, primary, Haberl, Manuela, primary, Elis, Winfried, primary, Kunz, Christian, primary, Heidt, Analeah B., primary, Herlihy, Kara, primary, Murtie, Joshua, primary, Schuller, Alwin, primary, Arteaga, Carlos L., primary, Sellers, William R., primary, and Ettenberg, Seth A., primary

Published
2023
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17. Supplementary Figure 1 from An Antibody That Locks HER3 in the Inactive Conformation Inhibits Tumor Growth Driven by HER2 or Neuregulin

Author

Garner, Andrew P., primary, Bialucha, Carl U., primary, Sprague, Elizabeth R., primary, Garrett, Joan T., primary, Sheng, Qing, primary, Li, Sharon, primary, Sineshchekova, Olga, primary, Saxena, Parmita, primary, Sutton, Cammie R., primary, Chen, Dongshu, primary, Chen, Yan, primary, Wang, Huiqin, primary, Liang, Jinsheng, primary, Das, Rita, primary, Mosher, Rebecca, primary, Gu, Jian, primary, Huang, Alan, primary, Haubst, Nicole, primary, Zehetmeier, Carolin, primary, Haberl, Manuela, primary, Elis, Winfried, primary, Kunz, Christian, primary, Heidt, Analeah B., primary, Herlihy, Kara, primary, Murtie, Joshua, primary, Schuller, Alwin, primary, Arteaga, Carlos L., primary, Sellers, William R., primary, and Ettenberg, Seth A., primary

Published
2023
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18. Supplementary Figure 2 from An Antibody That Locks HER3 in the Inactive Conformation Inhibits Tumor Growth Driven by HER2 or Neuregulin

Author

Garner, Andrew P., primary, Bialucha, Carl U., primary, Sprague, Elizabeth R., primary, Garrett, Joan T., primary, Sheng, Qing, primary, Li, Sharon, primary, Sineshchekova, Olga, primary, Saxena, Parmita, primary, Sutton, Cammie R., primary, Chen, Dongshu, primary, Chen, Yan, primary, Wang, Huiqin, primary, Liang, Jinsheng, primary, Das, Rita, primary, Mosher, Rebecca, primary, Gu, Jian, primary, Huang, Alan, primary, Haubst, Nicole, primary, Zehetmeier, Carolin, primary, Haberl, Manuela, primary, Elis, Winfried, primary, Kunz, Christian, primary, Heidt, Analeah B., primary, Herlihy, Kara, primary, Murtie, Joshua, primary, Schuller, Alwin, primary, Arteaga, Carlos L., primary, Sellers, William R., primary, and Ettenberg, Seth A., primary

Published
2023
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19. Supplementary Figure 8 from An Antibody That Locks HER3 in the Inactive Conformation Inhibits Tumor Growth Driven by HER2 or Neuregulin

Author

Garner, Andrew P., primary, Bialucha, Carl U., primary, Sprague, Elizabeth R., primary, Garrett, Joan T., primary, Sheng, Qing, primary, Li, Sharon, primary, Sineshchekova, Olga, primary, Saxena, Parmita, primary, Sutton, Cammie R., primary, Chen, Dongshu, primary, Chen, Yan, primary, Wang, Huiqin, primary, Liang, Jinsheng, primary, Das, Rita, primary, Mosher, Rebecca, primary, Gu, Jian, primary, Huang, Alan, primary, Haubst, Nicole, primary, Zehetmeier, Carolin, primary, Haberl, Manuela, primary, Elis, Winfried, primary, Kunz, Christian, primary, Heidt, Analeah B., primary, Herlihy, Kara, primary, Murtie, Joshua, primary, Schuller, Alwin, primary, Arteaga, Carlos L., primary, Sellers, William R., primary, and Ettenberg, Seth A., primary

Published
2023
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20. Supplementary Methods from An Antibody That Locks HER3 in the Inactive Conformation Inhibits Tumor Growth Driven by HER2 or Neuregulin

Author

Garner, Andrew P., primary, Bialucha, Carl U., primary, Sprague, Elizabeth R., primary, Garrett, Joan T., primary, Sheng, Qing, primary, Li, Sharon, primary, Sineshchekova, Olga, primary, Saxena, Parmita, primary, Sutton, Cammie R., primary, Chen, Dongshu, primary, Chen, Yan, primary, Wang, Huiqin, primary, Liang, Jinsheng, primary, Das, Rita, primary, Mosher, Rebecca, primary, Gu, Jian, primary, Huang, Alan, primary, Haubst, Nicole, primary, Zehetmeier, Carolin, primary, Haberl, Manuela, primary, Elis, Winfried, primary, Kunz, Christian, primary, Heidt, Analeah B., primary, Herlihy, Kara, primary, Murtie, Joshua, primary, Schuller, Alwin, primary, Arteaga, Carlos L., primary, Sellers, William R., primary, and Ettenberg, Seth A., primary

Published
2023
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21. Supplementary Figure 7 from An Antibody That Locks HER3 in the Inactive Conformation Inhibits Tumor Growth Driven by HER2 or Neuregulin

Author

Garner, Andrew P., primary, Bialucha, Carl U., primary, Sprague, Elizabeth R., primary, Garrett, Joan T., primary, Sheng, Qing, primary, Li, Sharon, primary, Sineshchekova, Olga, primary, Saxena, Parmita, primary, Sutton, Cammie R., primary, Chen, Dongshu, primary, Chen, Yan, primary, Wang, Huiqin, primary, Liang, Jinsheng, primary, Das, Rita, primary, Mosher, Rebecca, primary, Gu, Jian, primary, Huang, Alan, primary, Haubst, Nicole, primary, Zehetmeier, Carolin, primary, Haberl, Manuela, primary, Elis, Winfried, primary, Kunz, Christian, primary, Heidt, Analeah B., primary, Herlihy, Kara, primary, Murtie, Joshua, primary, Schuller, Alwin, primary, Arteaga, Carlos L., primary, Sellers, William R., primary, and Ettenberg, Seth A., primary

Published
2023
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22. Functional epigenetics approach identifies BRM/SMARCA2 as a critical synthetic lethal target in BRG1-deficient cancers

Author

Hoffman, Gregory R., Rahal, Rami, Buxton, Frank, Xiang, Kay, McAllister, Gregory, Frias, Elizabeth, Bagdasarian, Linda, Huber, Janina, Lindeman, Alicia, Chen, Dongshu, Romero, Rodrigo, Ramadan, Nadire, Phadke, Tanushree, Haas, Kristy, Jaskelioff, Mariela, Wilson, Boris G., Meyer, Matthew J., Saenz-Vash, Veronica, Zhai, Huili, Myer, Vic E., Porter, Jeffrey A., Keen, Nicholas, McLaughlin, Margaret E., Mickanin, Craig, Roberts, Charles W. M., Stegmeier, Frank, and Jagani, Zainab

Published
2014

24. Why passive sentences are used more frequently in Japanese than in Chinese : with a focus on Japanese translations from colloquial Chinese

Author

Chen, Dongshu

Subjects
視点の制約, 日中受身文, 中立の叙述, 対照言語学, 話し言葉
Abstract

研究論文, Articles, The aim of this article is to attempt to answer why passive sentences are employed more frequently in Japanese than in Chinese. This research is based on colloquial dialogues in Chinese TV dramas and movies with Japanese dubbing. The analysis of the frequency of passive sentences in both Japanese dubbing and the Chinese original versions showed that Japanese passive sentences are used 3.8 times more often than Chinese passive sentences. Furthermore, the survey revealed that 52.3% of passive sentences in Japanese dubbing are translated from active sentences of the original Chinese. The author proposes that the reason for the different ratio of passive sentences in the two languages is due to two important concepts in Japanese passive sentences, which the author calls "Conditional Perspective" and "Neutral Description". The "Conditional Perspective" can be divided into two subfactors, which are the "Personal Perspective" and the "Fixed Perspective". In Japanese the former is applied when the speaker describes an event involving a person or thing belonging to the speaker's "personal domain". In this case, the person or thing in question has to be expressed as the subject of the sentence, whether it is the agent or the recipient of an event. As for the latter subfactor, the subject has to remain the same unless there is a specific reason. The "Conditional Perspectives" on the other hand doesn't exist in Chinese. Therefore, even if a person or thing belonging to the speaker's "outer domain" is the agent of an event, an active sentence is generally used. In addition, in Chinese the subject does not have to be continuously the same. In consequence, by converting active Chinese sentences into passive Japanese phrases, the discordance between the target of empathy and its position n the sentence or discourse can be avoided. As for the "Neutral Description", the author found that passive sentences in Japanese are used in many circumstances ranging from influenced descriptions to neutral ones. Chinese "bei''constructions, however, always have a certain connotation of damage, thus making it difficult to express neutral events.

Published
2019

25. Loss of the tumor suppressor Snf5 leads to aberrant activation of the Hedgehog-Gli pathway

Author

Jagani, Zainab, Mora-Blanco, E. Lorena, Sansam, Courtney G., McKenna, Elizabeth S., Wilson, Boris, Chen, Dongshu, Klekota, Justin, Tamayo, Pablo, Nguyen, Phuong T.L., Tolstorukov, Michael, Park, Peter J., Cho, Yoon-Jae, Hsiao, Kathy, Buonamici, Silvia, Pomeroy, Scott L., Mesirov, Jill P., Ruffner, Heinz, Bouwmeester, Tewis, Luchansky, Sarah J., Murtie, Joshua, Kelleher, Joseph F., Warmuth, Markus, Sellers, William R., Roberts, Charles W.M., and Dorsch, Marion

Subjects
Tumors -- Risk factors -- Genetic aspects -- Research, Gene expression -- Research, Tumor suppressor genes -- Health aspects -- Research, Hedgehog proteins -- Physiological aspects -- Genetic aspects -- Research, Biological sciences, Health
Abstract

Aberrant activation of the Hedgehog (Hh) pathway can drive tumorigenesis (1). To investigate the mechanism by which glioma-associated oncogene family zinc finger-1 (GLI1), a crucial effector of Hh signaling (2), regulates Hh pathway activation, we searched for GLI1-interacting proteins. We report that the chromatin remodeling protein SNF5 (encoded by SMARCB1, hereafter called SNF5), which is inactivated in human malignant rhabdoid tumors (MRTs), interacts with GLI1. We show that Snf5 localizes to Gli1-regulated promoters and that loss of Snf5 leads to activation of the Hh-Gli pathway. Conversely, re-expression of SNF5 in MRT cells represses GLI1. Consistent with this, we show the presence of a Hh-Gli-activated gene expression profile in primary MRTs and show that GLI1 drives the growth of SNF5-deficient MRT cells in vitro and in vivo. Therefore, our studies reveal that SNF5 is a key mediator of Hh signaling and that aberrant activation of GLI1 is a previously undescribed targetable mechanism contributing to the growth of MRT cells., The Hh pathway has critical functions in tissue patterning and differentiation during development (1). Aberrant activation of the pathway resulting from mutations in the PTCH1 gene (encoding Patched-1 receptor) and [...]

Published
2010
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28. Development of Anti-CD32b Antibodies with Enhanced Fc Function for the Treatment of B and Plasma Cell Malignancies

Author

Lu, Haihui, primary, Molony, Ryan D., additional, Chen, Dongshu, additional, Jang, Sunyoung, additional, Wolf, Babette, additional, Ewert, Stefan, additional, Flaherty, Meghan, additional, Xu, Fangmin, additional, Isim, Sinan, additional, Shim, Yeonju, additional, Dornelas, Christina, additional, Balke, Nicole, additional, Leber, Xavier Charles, additional, Scharenberg, Meike, additional, Koelln, Johanna, additional, Choi, Eugene, additional, Ward, Rebecca, additional, Johnson, Jennifer, additional, Calzascia, Thomas, additional, Isnardi, Isabelle, additional, Williams, Juliet A., additional, Lindenbergh, Pieter L., additional, van de Donk, Niels W.C.J., additional, Mutis, Tuna, additional, Huet, Heather, additional, Lees, Emma, additional, and Meyer, Matthew J., additional

Published
2020
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29. Abstract C028: Discovery and characterization of next generation monoclonal antibodies targeting the inhibitory Fc gamma receptor CD32b for the treatment of B and plasma cell malignancies

Author

Lu, Haihui, primary, Chen, Dongshu, additional, Jang, Sunyoung, additional, Wolf, Babette, additional, Ewert, Stefan, additional, Flaherty, Meghan, additional, Xu, Fangmin, additional, Isim, Sinan, additional, Shim, Yeonjiu, additional, Dornelas, Christina, additional, Balke, Nicole, additional, Leber, Xavier Charles, additional, Scharenberg, Meike, additional, Koelln, Johanna, additional, Choi, Eugene, additional, Ward, Rebecca, additional, Johnson, Jennifer, additional, Calzascia, Thomas, additional, Isnardi, Isabelle, additional, Williams, Juliet, additional, Huet, Heather, additional, Lees, Emma, additional, and Meyer, Matthew J, additional

Published
2019
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39. Toward the Validation of Maternal Embryonic Leucine Zipper Kinase: Discovery, Optimization of Highly Potent and Selective Inhibitors, and Preliminary Biology Insight

Author

Toure, B. Barry, Giraldes, John, Smith, Troy, Sprague, Elizabeth R., Wang, Yaping, Mathieu, Simon, Chen, Zhuoliang, Mishina, Yuji, Feng, Yun, Yan-Neale, Yan, Shakya, Subarna, Chen, Dongshu, Meyer, Matthew, Puleo, David, Brazell, J. Tres, Straub, Christopher, Sage, David, Wright, Kirk, Yuan, Yanqiu, Chen, Xin, Duca, Jose, Kim, Sean, Tian, Li, Martin, Eric, Hurov, Kristen, Shao, Wenlin, Toure, B. Barry, Giraldes, John, Smith, Troy, Sprague, Elizabeth R., Wang, Yaping, Mathieu, Simon, Chen, Zhuoliang, Mishina, Yuji, Feng, Yun, Yan-Neale, Yan, Shakya, Subarna, Chen, Dongshu, Meyer, Matthew, Puleo, David, Brazell, J. Tres, Straub, Christopher, Sage, David, Wright, Kirk, Yuan, Yanqiu, Chen, Xin, Duca, Jose, Kim, Sean, Tian, Li, Martin, Eric, Hurov, Kristen, and Shao, Wenlin

Abstract

MELK kinase has been implicated in playing an important role in tumorigenesis. Our previous studies suggested that MELK is involved in the regulation of cell cycle and its genetic depletion leads to growth inhibition in a subset of high MELK-expressing basal-like breast cancer cell lines. Herein we describe the discovery and optimization of novel MELK inhibitors 8a and 8b that recapitulate the cellular effects observed by short hairpin ribonucleic acid (shRNA)-mediated MELK knockdown in cellular models. We also discovered a novel fluorine-induced hydrophobic collapse that locked the ligand in its bioactive conformation and led to a 20-fold gain in potency. These novel pharmacological inhibitors achieved high exposure in vivo and were well tolerated, which may allow further in vivo evaluation., MELK kinase has been implicated in playing an important role in tumorigenesis. Our previous studies suggested that MELK is involved in the regulation of cell cycle and its genetic depletion leads to growth inhibition in a subset of high MELK-expressing basal-like breast cancer cell lines. Herein we describe the discovery and optimization of novel MELK inhibitors 8a and 8b that recapitulate the cellular effects observed by short hairpin ribonucleic acid (shRNA)-mediated MELK knockdown in cellular models. We also discovered a novel fluorine-induced hydrophobic collapse that locked the ligand in its bioactive conformation and led to a 20-fold gain in potency. These novel pharmacological inhibitors achieved high exposure in vivo and were well tolerated, which may allow further in vivo evaluation.

Published
2016

40. Activation of antitumor cytotoxic T lymphocytes by fusions of human dendritic cells and breast carcinoma cells

Author

Gong, Jianlin, Avigan, David, Chen, Dongshu, Wu, Zekui, Koido, Shigeo, Kashiwaba, Masahiro, and Kufe, Donald

Subjects
Antigen presenting cells -- Research, Cancer -- Physiological aspects, Breast tumors -- Physiological aspects, Science and technology, National Academy of Sciences -- Research
Abstract

We have reported that fusions of murine dendritic cells (DCs) and murine carcinoma cells reverse unresponsiveness to tumor-associated antigens and induce the rejection of established metastases. In the present study, fusions were generated with primary human breast carcinoma cells and autologous DCs. Fusion cells coexpressed tumor-associated antigens and DC-derived costimulatory molecules. The fusion cells also retained the functional potency of DCs and stimulated autologous T cell proliferation. Significantly, the results show that autologous T cells are primed by the fusion cells to induce MHC class I-dependent lysis of autologous breast tumor cells. These findings demonstrate that fusions of human breast cancer cells and DCs activate T cell responses against autologous tumors. breast cancer | fusion cells | heterokaryons | DF3A/MUC1 antigen

Published
2000

41. Toward the Validation of Maternal Embryonic Leucine Zipper Kinase: Discovery, Optimization of Highly Potent and Selective Inhibitors, and Preliminary Biology Insight

Author

Touré, B. Barry, primary, Giraldes, John, additional, Smith, Troy, additional, Sprague, Elizabeth R., additional, Wang, Yaping, additional, Mathieu, Simon, additional, Chen, Zhuoliang, additional, Mishina, Yuji, additional, Feng, Yun, additional, Yan-Neale, Yan, additional, Shakya, Subarna, additional, Chen, Dongshu, additional, Meyer, Matthew, additional, Puleo, David, additional, Brazell, J. Tres, additional, Straub, Christopher, additional, Sage, David, additional, Wright, Kirk, additional, Yuan, Yanqiu, additional, Chen, Xin, additional, Duca, Jose, additional, Kim, Sean, additional, Tian, Li, additional, Martin, Eric, additional, Hurov, Kristen, additional, and Shao, Wenlin, additional

Published
2016
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42. Inhibition of Casein Kinase 1 Alpha Prevents Acquired Drug Resistance to Erlotinib in EGFR-Mutant Non–Small Cell Lung Cancer

Author

Lantermann, Alexandra B., primary, Chen, Dongshu, additional, McCutcheon, Kaitlin, additional, Hoffman, Greg, additional, Frias, Elizabeth, additional, Ruddy, David, additional, Rakiec, Daniel, additional, Korn, Joshua, additional, McAllister, Gregory, additional, Stegmeier, Frank, additional, Meyer, Matthew J., additional, and Sharma, Sreenath V., additional

Published
2015
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43. Abstract 1680: In vitro and in vivo activity of a highly potent and novel FGFR2/FGFR4 dual targeting antibody-drug conjugate

Author

Meyer, Matthew J., primary, Jenkins, David, additional, Batt, David, additional, Mosher, Rebecca, additional, Isaacs, Randi, additional, Hu, Tiancen, additional, Capka, Vladimir, additional, Zhang, Xiamei, additional, Chen, Dongshu, additional, Tang, Lujia, additional, Daley, Mike, additional, Nowakowski, Patrycja, additional, Shim, Yeonju, additional, Jiang, Wei, additional, Ettenberg, Seth, additional, and Lees, Emma, additional

Published
2015
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44. Abstract PR06: A functional screen of the epigenome identifies BRM/SMARCA2 as a critical synthetic lethal target in BRG1-deficient cancers.

Author

Jagani, Zainab, primary, Hoffman, Gregory, additional, Rahal, Rami, additional, Buxton, Frank, additional, McAllister, Gregory, additional, Xiang, Kay, additional, Frias, Elizabeth, additional, Huber, Janina, additional, Lindeman, Alicia, additional, Chen, Dongshu, additional, Bagdasarian, Linda, additional, Romero, Rodrigo, additional, Ramadan, Nadire, additional, Phadke, Tanushree, additional, Haas, Kristy, additional, Jaskelioff, Mariela, additional, Wilson, Boris, additional, Meyer, Matthew, additional, McLaughlin, Margaret E., additional, Roberts, Charles WM, additional, Myer, Vic, additional, Porter, Jeff, additional, Keen, Nicholas, additional, Mickanin, Craig, additional, and Stegmeier, Frank, additional

Published
2013
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45. An Antibody That Locks HER3 in the Inactive Conformation Inhibits Tumor Growth Driven by HER2 or Neuregulin

Author

Garner, Andrew P., primary, Bialucha, Carl U., additional, Sprague, Elizabeth R., additional, Garrett, Joan T., additional, Sheng, Qing, additional, Li, Sharon, additional, Sineshchekova, Olga, additional, Saxena, Parmita, additional, Sutton, Cammie R., additional, Chen, Dongshu, additional, Chen, Yan, additional, Wang, Huiqin, additional, Liang, Jinsheng, additional, Das, Rita, additional, Mosher, Rebecca, additional, Gu, Jian, additional, Huang, Alan, additional, Haubst, Nicole, additional, Zehetmeier, Carolin, additional, Haberl, Manuela, additional, Elis, Winfried, additional, Kunz, Christian, additional, Heidt, Analeah B., additional, Herlihy, Kara, additional, Murtie, Joshua, additional, Schuller, Alwin, additional, Arteaga, Carlos L., additional, Sellers, William R., additional, and Ettenberg, Seth A., additional

Published
2013
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46. Abstract 2733: LJM716: an anti-HER3 antibody that inhibits both HER2 and NRG driven tumor growth by trapping HER3 in the inactive conformation.

Author

Garner, Andrew, primary, Sheng, Qing, additional, Bialucha, Uli, additional, Chen, Dongshu, additional, Chen, Yan, additional, Das, Rita, additional, Elis, Winfried, additional, Heidt, Analeah, additional, Kunz, Christian, additional, Li, Sharon, additional, Liang, Jinsheng, additional, Murtie, Joshua, additional, Saxena, Parmita, additional, Schuller, Alwin, additional, Sineshchekova, Olga, additional, Sprague, Elizabeth, additional, Wang, Hui Qin, additional, Huang, Alan, additional, and Ettenberg, Seth, additional

Published
2012
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