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259 results on '"Wu, Xiaochong"'

1. Early rhombic lip Protogenin+ve stem cells in a human-specific neurovascular niche initiate and maintain group 3 medulloblastoma

Author

Visvanathan, Abhirami, Saulnier, Olivier, Chen, Chuan, Haldipur, Parthiv, Orisme, Wilda, Delaidelli, Alberto, Shin, Seungmin, Millman, Jake, Bryant, Andrew, Abeysundara, Namal, Wu, Xujia, Hendrikse, Liam D., Patil, Vikas, Bashardanesh, Zahedeh, Golser, Joseph, Livingston, Bryn G., Nakashima, Takuma, Funakoshi, Yusuke, Ong, Winnie, Rasnitsyn, Alexandra, Aldinger, Kimberly A., Richman, Cory M., Van Ommeren, Randy, Lee, John J.Y., Ly, Michelle, Vladoiu, Maria C., Kharas, Kaitlin, Balin, Polina, Erickson, Anders W., Fong, Vernon, Zhang, Jiao, Suárez, Raúl A., Wang, Hao, Huang, Ning, Pallota, Jonelle G., Douglas, Tajana, Haapasalo, Joonas, Razavi, Ferechte, Silvestri, Evelina, Sirbu, Olga, Worme, Samantha, Kameda-Smith, Michelle M., Wu, Xiaochong, Daniels, Craig, MichaelRaj, Antony K., Bhaduri, Aparna, Schramek, Daniel, Suzuki, Hiromichi, Garzia, Livia, Ahmed, Nabil, Kleinman, Claudia L., Stein, Lincoln D., Dirks, Peter, Dunham, Christopher, Jabado, Nada, Rich, Jeremy N., Li, Wei, Sorensen, Poul H., Wechsler-Reya, Robert J., Weiss, William A., Millen, Kathleen J., Ellison, David W., Dimitrov, Dimiter S., and Taylor, Michael D.

Published
2024
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3. Multi-directional Force and Tactile Sensor Sleeves for Micro Catheters and Cannulas

Author

Sogunro, Joelle, Wu, Xiaochong, Saija, Carlo, Alabdullah, Basma, Rowell, Joseph, Liu, Anhao, Fernandez, Cristina Sanchez, Rhode, Kawal, Bergeles, Christos, Sadati, S. M. Hadi, Goos, Gerhard, Founding Editor, Hartmanis, Juris, Founding Editor, Bertino, Elisa, Editorial Board Member, Gao, Wen, Editorial Board Member, Steffen, Bernhard, Editorial Board Member, Yung, Moti, Editorial Board Member, Iida, Fumiya, editor, Maiolino, Perla, editor, Abdulali, Arsen, editor, and Wang, Mingfeng, editor

Published
2023
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4. The transcriptional landscape of Shh medulloblastoma.

Author

Skowron, Patryk, Farooq, Hamza, Cavalli, Florence MG, Morrissy, A Sorana, Ly, Michelle, Hendrikse, Liam D, Wang, Evan Y, Djambazian, Haig, Zhu, Helen, Mungall, Karen L, Trinh, Quang M, Zheng, Tina, Dai, Shizhong, Stucklin, Ana S Guerreiro, Vladoiu, Maria C, Fong, Vernon, Holgado, Borja L, Nor, Carolina, Wu, Xiaochong, Abd-Rabbo, Diala, Bérubé, Pierre, Wang, Yu Chang, Luu, Betty, Suarez, Raul A, Rastan, Avesta, Gillmor, Aaron H, Lee, John JY, Zhang, Xiao Yun, Daniels, Craig, Dirks, Peter, Malkin, David, Bouffet, Eric, Tabori, Uri, Loukides, James, Doz, François P, Bourdeaut, Franck, Delattre, Olivier O, Masliah-Planchon, Julien, Ayrault, Olivier, Kim, Seung-Ki, Meyronet, David, Grajkowska, Wieslawa A, Carlotti, Carlos G, de Torres, Carmen, Mora, Jaume, Eberhart, Charles G, Van Meir, Erwin G, Kumabe, Toshihiro, French, Pim J, Kros, Johan M, Jabado, Nada, Lach, Boleslaw, Pollack, Ian F, Hamilton, Ronald L, Rao, Amulya A Nageswara, Giannini, Caterina, Olson, James M, Bognár, László, Klekner, Almos, Zitterbart, Karel, Phillips, Joanna J, Thompson, Reid C, Cooper, Michael K, Rubin, Joshua B, Liau, Linda M, Garami, Miklós, Hauser, Peter, Li, Kay Ka Wai, Ng, Ho-Keung, Poon, Wai Sang, Yancey Gillespie, G, Chan, Jennifer A, Jung, Shin, McLendon, Roger E, Thompson, Eric M, Zagzag, David, Vibhakar, Rajeev, Ra, Young Shin, Garre, Maria Luisa, Schüller, Ulrich, Shofuda, Tomoko, Faria, Claudia C, López-Aguilar, Enrique, Zadeh, Gelareh, Hui, Chi-Chung, Ramaswamy, Vijay, Bailey, Swneke D, Jones, Steven J, Mungall, Andrew J, Moore, Richard A, Calarco, John A, Stein, Lincoln D, Bader, Gary D, Reimand, Jüri, Ragoussis, Jiannis, Weiss, William A, Marra, Marco A, Suzuki, Hiromichi, and Taylor, Michael D

Subjects
Humans, Medulloblastoma, Cerebellar Neoplasms, Signal Transduction, Gene Expression Regulation, Neoplastic, Adolescent, Adult, Middle Aged, Child, Child, Preschool, Infant, Female, Male, Hedgehog Proteins, Gene Regulatory Networks, Genetic Variation, Young Adult, Transcriptome, Pediatric Research Initiative, Brain Cancer, Pediatric, Rare Diseases, Genetics, Pediatric Cancer, Clinical Research, Brain Disorders, Neurosciences, Biotechnology, Human Genome, Cancer, 2.1 Biological and endogenous factors
Abstract

Sonic hedgehog medulloblastoma encompasses a clinically and molecularly diverse group of cancers of the developing central nervous system. Here, we use unbiased sequencing of the transcriptome across a large cohort of 250 tumors to reveal differences among molecular subtypes of the disease, and demonstrate the previously unappreciated importance of non-coding RNA transcripts. We identify alterations within the cAMP dependent pathway (GNAS, PRKAR1A) which converge on GLI2 activity and show that 18% of tumors have a genetic event that directly targets the abundance and/or stability of MYCN. Furthermore, we discover an extensive network of fusions in focally amplified regions encompassing GLI2, and several loss-of-function fusions in tumor suppressor genes PTCH1, SUFU and NCOR1. Molecular convergence on a subset of genes by nucleotide variants, copy number aberrations, and gene fusions highlight the key roles of specific pathways in the pathogenesis of Sonic hedgehog medulloblastoma and open up opportunities for therapeutic intervention.

Published
2021

5. Failure of human rhombic lip differentiation underlies medulloblastoma formation

Author

Hendrikse, Liam D., Haldipur, Parthiv, Saulnier, Olivier, Millman, Jake, Sjoboen, Alexandria H., Erickson, Anders W., Ong, Winnie, Gordon, Victor, Coudière-Morrison, Ludivine, Mercier, Audrey L., Shokouhian, Mohammad, Suárez, Raúl A., Ly, Michelle, Borlase, Stephanie, Scott, David S., Vladoiu, Maria C., Farooq, Hamza, Sirbu, Olga, Nakashima, Takuma, Nambu, Shohei, Funakoshi, Yusuke, Bahcheli, Alec, Diaz-Mejia, J. Javier, Golser, Joseph, Bach, Kathleen, Phuong-Bao, Tram, Skowron, Patryk, Wang, Evan Y., Kumar, Sachin A., Balin, Polina, Visvanathan, Abhirami, Lee, John J. Y., Ayoub, Ramy, Chen, Xin, Chen, Xiaodi, Mungall, Karen L., Luu, Betty, Bérubé, Pierre, Wang, Yu C., Pfister, Stefan M., Kim, Seung-Ki, Delattre, Olivier, Bourdeaut, Franck, Doz, François, Masliah-Planchon, Julien, Grajkowska, Wieslawa A., Loukides, James, Dirks, Peter, Fèvre-Montange, Michelle, Jouvet, Anne, French, Pim J., Kros, Johan M., Zitterbart, Karel, Bailey, Swneke D., Eberhart, Charles G., Rao, Amulya A. N., Giannini, Caterina, Olson, James M., Garami, Miklós, Hauser, Peter, Phillips, Joanna J., Ra, Young S., de Torres, Carmen, Mora, Jaume, Li, Kay K. W., Ng, Ho-Keung, Poon, Wai S., Pollack, Ian F., López-Aguilar, Enrique, Gillespie, G. Yancey, Van Meter, Timothy E., Shofuda, Tomoko, Vibhakar, Rajeev, Thompson, Reid C., Cooper, Michael K., Rubin, Joshua B., Kumabe, Toshihiro, Jung, Shin, Lach, Boleslaw, Iolascon, Achille, Ferrucci, Veronica, de Antonellis, Pasqualino, Zollo, Massimo, Cinalli, Giuseppe, Robinson, Shenandoah, Stearns, Duncan S., Van Meir, Erwin G., Porrati, Paola, Finocchiaro, Gaetano, Massimino, Maura, Carlotti, Carlos G., Faria, Claudia C., Roussel, Martine F., Boop, Frederick, Chan, Jennifer A., Aldinger, Kimberly A., Razavi, Ferechte, Silvestri, Evelina, McLendon, Roger E., Thompson, Eric M., Ansari, Marc, Garre, Maria L., Chico, Fernando, Eguía, Pilar, Pérezpeña, Mario, Morrissy, A. Sorana, Cavalli, Florence M. G., Wu, Xiaochong, Daniels, Craig, Rich, Jeremy N., Jones, Steven J. M., Moore, Richard A., Marra, Marco A., Huang, Xi, Reimand, Jüri, Sorensen, Poul H., Wechsler-Reya, Robert J., Weiss, William A., Pugh, Trevor J., Garzia, Livia, Kleinman, Claudia L., Stein, Lincoln D., Jabado, Nada, Malkin, David, Ayrault, Olivier, Golden, Jeffrey A., Ellison, David W., Doble, Brad, Ramaswamy, Vijay, Werbowetski-Ogilvie, Tamra E., Suzuki, Hiromichi, Millen, Kathleen J., and Taylor, Michael D.

Published
2022
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6. A Hematogenous Route for Medulloblastoma Leptomeningeal Metastases

Author

Garzia, Livia, Kijima, Noriyuki, Morrissy, A Sorana, De Antonellis, Pasqualino, Guerreiro-Stucklin, Ana, Holgado, Borja L, Wu, Xiaochong, Wang, Xin, Parsons, Michael, Zayne, Kory, Manno, Alex, Kuzan-Fischer, Claudia, Nor, Carolina, Donovan, Laura K, Liu, Jessica, Qin, Lei, Garancher, Alexandra, Liu, Kun-Wei, Mansouri, Sheila, Luu, Betty, Thompson, Yuan Yao, Ramaswamy, Vijay, Peacock, John, Farooq, Hamza, Skowron, Patryk, Shih, David JH, Li, Angela, Ensan, Sherine, Robbins, Clinton S, Cybulsky, Myron, Mitra, Siddhartha, Ma, Yussanne, Moore, Richard, Mungall, Andy, Cho, Yoon-Jae, Weiss, William A, Chan, Jennifer A, Hawkins, Cynthia E, Massimino, Maura, Jabado, Nada, Zapotocky, Michal, Sumerauer, David, Bouffet, Eric, Dirks, Peter, Tabori, Uri, Sorensen, Poul HB, Brastianos, Priscilla K, Aldape, Kenneth, Jones, Steven JM, Marra, Marco A, Woodgett, James R, Wechsler-Reya, Robert J, Fults, Daniel W, and Taylor, Michael D

Subjects
Brain Cancer, Cancer, Neurosciences, Pediatric Cancer, Pediatric, Rare Diseases, Brain Disorders, Allografts, Animals, Cell Line, Tumor, Chemokine CCL2, Chromosomes, Human, Pair 10, Female, Humans, Male, Medulloblastoma, Meningeal Neoplasms, Mice, SCID, Neoplastic Cells, Circulating, Parabiosis, brain tumors, circulating tumor cells, medulloblastoma, metastases, pediatric cancer, Biological Sciences, Medical and Health Sciences, Developmental Biology
Abstract

While the preponderance of morbidity and mortality in medulloblastoma patients are due to metastatic disease, most research focuses on the primary tumor due to a dearth of metastatic tissue samples and model systems. Medulloblastoma metastases are found almost exclusively on the leptomeningeal surface of the brain and spinal cord; dissemination is therefore thought to occur through shedding of primary tumor cells into the cerebrospinal fluid followed by distal re-implantation on the leptomeninges. We present evidence for medulloblastoma circulating tumor cells (CTCs) in therapy-naive patients and demonstrate in vivo, through flank xenografting and parabiosis, that medulloblastoma CTCs can spread through the blood to the leptomeningeal space to form leptomeningeal metastases. Medulloblastoma leptomeningeal metastases express high levels of the chemokine CCL2, and expression of CCL2 in medulloblastoma in vivo is sufficient to drive leptomeningeal dissemination. Hematogenous dissemination of medulloblastoma offers a new opportunity to diagnose and treat lethal disseminated medulloblastoma.

Published
2018

7. The whole-genome landscape of medulloblastoma subtypes

Author

Northcott, Paul A, Buchhalter, Ivo, Morrissy, A Sorana, Hovestadt, Volker, Weischenfeldt, Joachim, Ehrenberger, Tobias, Gröbner, Susanne, Segura-Wang, Maia, Zichner, Thomas, Rudneva, Vasilisa A, Warnatz, Hans-Jörg, Sidiropoulos, Nikos, Phillips, Aaron H, Schumacher, Steven, Kleinheinz, Kortine, Waszak, Sebastian M, Erkek, Serap, Jones, David TW, Worst, Barbara C, Kool, Marcel, Zapatka, Marc, Jäger, Natalie, Chavez, Lukas, Hutter, Barbara, Bieg, Matthias, Paramasivam, Nagarajan, Heinold, Michael, Gu, Zuguang, Ishaque, Naveed, Jäger-Schmidt, Christina, Imbusch, Charles D, Jugold, Alke, Hübschmann, Daniel, Risch, Thomas, Amstislavskiy, Vyacheslav, Gonzalez, Francisco German Rodriguez, Weber, Ursula D, Wolf, Stephan, Robinson, Giles W, Zhou, Xin, Wu, Gang, Finkelstein, David, Liu, Yanling, Cavalli, Florence MG, Luu, Betty, Ramaswamy, Vijay, Wu, Xiaochong, Koster, Jan, Ryzhova, Marina, Cho, Yoon-Jae, Pomeroy, Scott L, Herold-Mende, Christel, Schuhmann, Martin, Ebinger, Martin, Liau, Linda M, Mora, Jaume, McLendon, Roger E, Jabado, Nada, Kumabe, Toshihiro, Chuah, Eric, Ma, Yussanne, Moore, Richard A, Mungall, Andrew J, Mungall, Karen L, Thiessen, Nina, Tse, Kane, Wong, Tina, Jones, Steven JM, Witt, Olaf, Milde, Till, Von Deimling, Andreas, Capper, David, Korshunov, Andrey, Yaspo, Marie-Laure, Kriwacki, Richard, Gajjar, Amar, Zhang, Jinghui, Beroukhim, Rameen, Fraenkel, Ernest, Korbel, Jan O, Brors, Benedikt, Schlesner, Matthias, Eils, Roland, Marra, Marco A, Pfister, Stefan M, Taylor, Michael D, and Lichter, Peter

Subjects
Cancer, Human Genome, Brain Disorders, Pediatric Cancer, Brain Cancer, Genetics, Biotechnology, Rare Diseases, Neurosciences, Pediatric, Aetiology, 2.1 Biological and endogenous factors, Development of treatments and therapeutic interventions, 5.1 Pharmaceuticals, Good Health and Well Being, Carcinogenesis, Carrier Proteins, Cohort Studies, DNA Methylation, DNA Mutational Analysis, Datasets as Topic, Epistasis, Genetic, Genome, Human, Genomics, Humans, Medulloblastoma, Molecular Targeted Therapy, Muscle Proteins, Mutation, Oncogenes, Transcription Factors, Whole Genome Sequencing, Wnt Proteins, General Science & Technology
Abstract

Current therapies for medulloblastoma, a highly malignant childhood brain tumour, impose debilitating effects on the developing child, and highlight the need for molecularly targeted treatments with reduced toxicity. Previous studies have been unable to identify the full spectrum of driver genes and molecular processes that operate in medulloblastoma subgroups. Here we analyse the somatic landscape across 491 sequenced medulloblastoma samples and the molecular heterogeneity among 1,256 epigenetically analysed cases, and identify subgroup-specific driver alterations that include previously undiscovered actionable targets. Driver mutations were confidently assigned to most patients belonging to Group 3 and Group 4 medulloblastoma subgroups, greatly enhancing previous knowledge. New molecular subtypes were differentially enriched for specific driver events, including hotspot in-frame insertions that target KBTBD4 and 'enhancer hijacking' events that activate PRDM6. Thus, the application of integrative genomics to an extensive cohort of clinical samples derived from a single childhood cancer entity revealed a series of cancer genes and biologically relevant subtype diversity that represent attractive therapeutic targets for the treatment of patients with medulloblastoma.

Published
2017

8. Author Correction: Locoregional delivery of CAR T cells to the cerebrospinal fluid for treatment of metastatic medulloblastoma and ependymoma

Author

Donovan, Laura K., Delaidelli, Alberto, Joseph, Sujith K., Bielamowicz, Kevin, Fousek, Kristen, Holgado, Borja L., Manno, Alex, Srikanthan, Dilakshan, Gad, Ahmed Z., Van Ommeren, Randy, Przelicki, David, Richman, Cory, Ramaswamy, Vijay, Daniels, Craig, Pallota, Jonelle G., Douglas, Tajana, Joynt, Alyssa C. M., Haapasalo, Joonas, Nor, Carolina, Vladoiu, Maria C., Kuzan-Fischer, Claudia M., Garzia, Livia, Mack, Stephen C., Varadharajan, Srinidhi, Baker, Matthew L., Hendrikse, Liam, Ly, Michelle, Kharas, Kaitlin, Balin, Polina, Wu, Xiaochong, Qin, Lei, Huang, Ning, Stucklin, Ana Guerreiro, Morrissy, A. Sorana, Cavalli, Florence M. G., Luu, Betty, Suarez, Raul, De Antonellis, Pasqualino, Michealraj, Antony, Rastan, Avesta, Hegde, Meenakshi, Komosa, Martin, Sirbu, Olga, Kumar, Sachin A., Abdullaev, Zied, Faria, Claudia C., Yip, Stephen, Hukin, Juliette, Tabori, Uri, Hawkins, Cynthia, Aldape, Ken, Daugaard, Mads, Maris, John M., Sorensen, Poul H., Ahmed, Nabil, and Taylor, Michael D.

Published
2021
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9. Author Correction: Failure of human rhombic lip differentiation underlies medulloblastoma formation

Author

Hendrikse, Liam D., Haldipur, Parthiv, Saulnier, Olivier, Millman, Jake, Sjoboen, Alexandria H., Erickson, Anders W., Ong, Winnie, Gordon, Victor, Coudière-Morrison, Ludivine, Mercier, Audrey L., Shokouhian, Mohammad, Suárez, Raúl A., Ly, Michelle, Borlase, Stephanie, Scott, David S., Vladoiu, Maria C., Farooq, Hamza, Sirbu, Olga, Nakashima, Takuma, Nambu, Shohei, Funakoshi, Yusuke, Bahcheli, Alec, Diaz-Mejia, J. Javier, Golser, Joseph, Bach, Kathleen, Phuong-Bao, Tram, Skowron, Patryk, Wang, Evan Y., Kumar, Sachin A., Balin, Polina, Visvanathan, Abhirami, Lee, John J. Y., Ayoub, Ramy, Chen, Xin, Chen, Xiaodi, Mungall, Karen L., Luu, Betty, Bérubé, Pierre, Wang, Yu C., Pfister, Stefan M., Kim, Seung-Ki, Delattre, Olivier, Bourdeaut, Franck, Doz, François, Masliah-Planchon, Julien, Grajkowska, Wieslawa A., Loukides, James, Dirks, Peter, Fèvre-Montange, Michelle, Jouvet, Anne, French, Pim J., Kros, Johan M., Zitterbart, Karel, Bailey, Swneke D., Eberhart, Charles G., Rao, Amulya A. N., Giannini, Caterina, Olson, James M., Garami, Miklós, Hauser, Peter, Phillips, Joanna J., Ra, Young S., de Torres, Carmen, Mora, Jaume, Li, Kay K. W., Ng, Ho-Keung, Poon, Wai S., Pollack, Ian F., López-Aguilar, Enrique, Gillespie, G. Yancey, Van Meter, Timothy E., Shofuda, Tomoko, Vibhakar, Rajeev, Thompson, Reid C., Cooper, Michael K., Rubin, Joshua B., Kumabe, Toshihiro, Jung, Shin, Lach, Boleslaw, Iolascon, Achille, Ferrucci, Veronica, de Antonellis, Pasqualino, Zollo, Massimo, Cinalli, Giuseppe, Robinson, Shenandoah, Stearns, Duncan S., Van Meir, Erwin G., Porrati, Paola, Finocchiaro, Gaetano, Massimino, Maura, Carlotti, Carlos G., Faria, Claudia C., Roussel, Martine F., Boop, Frederick, Chan, Jennifer A., Aldinger, Kimberly A., Razavi, Ferechte, Silvestri, Evelina, McLendon, Roger E., Thompson, Eric M., Ansari, Marc, Garre, Maria L., Chico, Fernando, Eguía, Pilar, Pérezpeña, Mario, Morrissy, A. Sorana, Cavalli, Florence M. G., Wu, Xiaochong, Daniels, Craig, Rich, Jeremy N., Jones, Steven J. M., Moore, Richard A., Marra, Marco A., Huang, Xi, Reimand, Jüri, Sorensen, Poul H., Wechsler-Reya, Robert J., Weiss, William A., Pugh, Trevor J., Garzia, Livia, Kleinman, Claudia L., Stein, Lincoln D., Jabado, Nada, Malkin, David, Ayrault, Olivier, Golden, Jeffrey A., Ellison, David W., Doble, Brad, Ramaswamy, Vijay, Werbowetski-Ogilvie, Tamra E., Suzuki, Hiromichi, Millen, Kathleen J., and Taylor, Michael D.

Published
2022
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10. Divergent clonal selection dominates medulloblastoma at recurrence

Author

Morrissy, A Sorana, Garzia, Livia, Shih, David JH, Zuyderduyn, Scott, Huang, Xi, Skowron, Patryk, Remke, Marc, Cavalli, Florence MG, Ramaswamy, Vijay, Lindsay, Patricia E, Jelveh, Salomeh, Donovan, Laura K, Wang, Xin, Luu, Betty, Zayne, Kory, Li, Yisu, Mayoh, Chelsea, Thiessen, Nina, Mercier, Eloi, Mungall, Karen L, Ma, Yusanne, Tse, Kane, Zeng, Thomas, Shumansky, Karey, Roth, Andrew JL, Shah, Sohrab, Farooq, Hamza, Kijima, Noriyuki, Holgado, Borja L, Lee, John JY, Matan-Lithwick, Stuart, Liu, Jessica, Mack, Stephen C, Manno, Alex, Michealraj, KA, Nor, Carolina, Peacock, John, Qin, Lei, Reimand, Juri, Rolider, Adi, Thompson, Yuan Y, Wu, Xiaochong, Pugh, Trevor, Ally, Adrian, Bilenky, Mikhail, Butterfield, Yaron SN, Carlsen, Rebecca, Cheng, Young, Chuah, Eric, Corbett, Richard D, Dhalla, Noreen, He, An, Lee, Darlene, Li, Haiyan I, Long, William, Mayo, Michael, Plettner, Patrick, Qian, Jenny Q, Schein, Jacqueline E, Tam, Angela, Wong, Tina, Birol, Inanc, Zhao, Yongjun, Faria, Claudia C, Pimentel, José, Nunes, Sofia, Shalaby, Tarek, Grotzer, Michael, Pollack, Ian F, Hamilton, Ronald L, Li, Xiao-Nan, Bendel, Anne E, Fults, Daniel W, Walter, Andrew W, Kumabe, Toshihiro, Tominaga, Teiji, Collins, V Peter, Cho, Yoon-Jae, Hoffman, Caitlin, Lyden, David, Wisoff, Jeffrey H, Garvin, James H, Stearns, Duncan S, Massimi, Luca, Schüller, Ulrich, Sterba, Jaroslav, Zitterbart, Karel, Puget, Stephanie, Ayrault, Olivier, Dunn, Sandra E, Tirapelli, Daniela PC, Carlotti, Carlos G, Wheeler, Helen, Hallahan, Andrew R, Ingram, Wendy, MacDonald, Tobey J, Olson, Jeffrey J, Van Meir, Erwin G, Lee, Ji-Yeoun, and Wang, Kyu-Chang

Subjects
Pediatric, Biotechnology, Genetics, Brain Disorders, Human Genome, Brain Cancer, Rare Diseases, Cancer, Animals, Cerebellar Neoplasms, Clone Cells, Craniospinal Irradiation, DNA Mutational Analysis, Disease Models, Animal, Drosophila melanogaster, Female, Genome, Human, Humans, Male, Medulloblastoma, Mice, Molecular Targeted Therapy, Neoplasm Recurrence, Local, Radiotherapy, Image-Guided, Selection, Genetic, Signal Transduction, Xenograft Model Antitumor Assays, General Science & Technology
Abstract

The development of targeted anti-cancer therapies through the study of cancer genomes is intended to increase survival rates and decrease treatment-related toxicity. We treated a transposon-driven, functional genomic mouse model of medulloblastoma with 'humanized' in vivo therapy (microneurosurgical tumour resection followed by multi-fractionated, image-guided radiotherapy). Genetic events in recurrent murine medulloblastoma exhibit a very poor overlap with those in matched murine diagnostic samples (

Published
2016

12. Locoregional delivery of CAR T cells to the cerebrospinal fluid for treatment of metastatic medulloblastoma and ependymoma

Author

Donovan, Laura K., Delaidelli, Alberto, Joseph, Sujith K., Bielamowicz, Kevin, Fousek, Kristen, Holgado, Borja L., Manno, Alex, Srikanthan, Dilakshan, Gad, Ahmed Z., Van Ommeren, Randy, Przelicki, David, Richman, Cory, Ramaswamy, Vijay, Daniels, Craig, Pallota, Jonelle G., Douglas, Tajana, Joynt, Alyssa C.M., Haapasalo, Joonas, Nor, Carolina, Vladoiu, Maria C., Kuzan-Fischer, Claudia M., Garzia, Livia, Mack, Stephen C., Varadharajan, Srinidhi, Baker, Matthew L., Hendrikse, Liam, Ly, Michelle, Kharas, Kaitlin, Balin, Polina, Wu, Xiaochong, Qin, Lei, Huang, Ning, Stucklin, Ana Guerreiro, Morrissy, A. Sorana, Cavalli, Florence M.G., Luu, Betty, Suarez, Raul, De Antonellis, Pasqualino, Michealraj, Antony, Rastan, Avesta, Hegde, Meenakshi, Komosa, Martin, Sirbu, Olga, Kumar, Sachin A., Abdullaev, Zied, Faria, Claudia C., Yip, Stephen, Hukin, Juliette, Tabori, Uri, Hawkins, Cynthia, Aldape, Ken, Daugaard, Mads, Maris, John M., Sorenson, Poul H., Ahmed, Nabil, and Taylor, Michael D.

Subjects
T cells -- Health aspects -- Methods, Medulloblastoma -- Care and treatment, Metastasis -- Care and treatment, Cellular therapy -- Methods -- Health aspects, Immunotherapy -- Methods -- Health aspects, Antigens -- Health aspects, Cerebrospinal fluid -- Health aspects -- Methods, Biological sciences, Health
Abstract

Recurrent medulloblastoma and ependymoma are universally lethal, with no approved targeted therapies and few candidates presently under clinical evaluation. Nearly all recurrent medulloblastomas and posterior fossa group A (PFA) ependymomas are located adjacent to and bathed by the cerebrospinal fluid, presenting an opportunity for locoregional therapy, bypassing the blood-brain barrier. We identify three cell-surface targets, EPHA2, HER2 and interleukin 13 receptor [alpha]2, expressed on medulloblastomas and ependymomas, but not expressed in the normal developing brain. We validate intrathecal delivery of EPHA2, HER2 and interleukin 13 receptor [alpha]2 chimeric antigen receptor T cells as an effective treatment for primary, metastatic and recurrent group 3 medulloblastoma and PFA ependymoma xenografts in mouse models. Finally, we demonstrate that administration of these chimeric antigen receptor T cells into the cerebrospinal fluid, alone or in combination with azacytidine, is a highly effective therapy for multiple metastatic mouse models of group 3 medulloblastoma and PFA ependymoma, thereby providing a rationale for clinical trials of these approaches in humans. Intraventricularly delivered monovalent and trivalent CAR T cells exhibit greater therapeutic efficacy as compared with intravenously delivered CAR T cells in medulloblastoma xenograft mouse models and show potency in ependymoma xenograft mouse models., Author(s): Laura K. Donovan [sup.1] [sup.2] , Alberto Delaidelli [sup.3] , Sujith K. Joseph [sup.4] [sup.5] , Kevin Bielamowicz [sup.4] [sup.5] , Kristen Fousek [sup.4] [sup.5] , Borja L. Holgado [...]

Published
2020
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13. EAG2 potassium channel with evolutionarily conserved function as a brain tumor target.

Author

Huang, Xi, He, Ye, Dubuc, Adrian, Hashizume, Rintaro, Zhang, Wei, Reimand, Jüri, Yang, Huanghe, Wang, Tongfei, Stehbens, Samantha, Younger, Susan, Barshow, Suzanne, Zhu, Sijun, Cooper, Michael, Peacock, John, Ramaswamy, Vijay, Garzia, Livia, Wu, Xiaochong, Remke, Marc, Forester, Craig, Bader, Gary, Mueller, Sabine, Taylor, Michael, James, C, Shuman, Marc, Weiss, William, Kim, Charles, Jan, Lily, and Jan, Yuh

Subjects
Animals, Brain Neoplasms, COS Cells, Chlorocebus aethiops, Drosophila, Drug Delivery Systems, Ether-A-Go-Go Potassium Channels, Evolution, Molecular, Female, Humans, Male, Mice, Mice, Inbred BALB C, Mice, Nude, Mice, Transgenic, Thioridazine, Tumor Cells, Cultured, Xenograft Model Antitumor Assays, Young Adult
Abstract

Over 20% of the drugs for treating human diseases target ion channels, but no cancer drug approved by the US Food and Drug Administration (FDA) is intended to target an ion channel. We found that the EAG2 (Ether-a-go-go 2) potassium channel has an evolutionarily conserved function for promoting brain tumor growth and metastasis, delineate downstream pathways, and uncover a mechanism for different potassium channels to functionally cooperate and regulate mitotic cell volume and tumor progression. EAG2 potassium channel was enriched at the trailing edge of migrating medulloblastoma (MB) cells to regulate local cell volume dynamics, thereby facilitating cell motility. We identified the FDA-approved antipsychotic drug thioridazine as an EAG2 channel blocker that reduces xenografted MB growth and metastasis, and present a case report of repurposing thioridazine for treating a human patient. Our findings illustrate the potential of targeting ion channels in cancer treatment.

Published
2015

14. Cytogenetic prognostication within medulloblastoma subgroups.

Author

Shih, David, Northcott, Paul, Remke, Marc, Korshunov, Andrey, Ramaswamy, Vijay, Kool, Marcel, Luu, Betty, Yao, Yuan, Wang, Xin, Dubuc, Adrian, Garzia, Livia, Peacock, John, Mack, Stephen, Wu, Xiaochong, Rolider, Adi, Morrissy, A, Cavalli, Florence, Jones, David, Zitterbart, Karel, Faria, Claudia, Schüller, Ulrich, Kren, Leos, Kumabe, Toshihiro, Tominaga, Teiji, Shin Ra, Young, Garami, Miklós, Hauser, Peter, Chan, Jennifer, Robinson, Shenandoah, Bognár, László, Klekner, Almos, Saad, Ali, Albrecht, Steffen, Fontebasso, Adam, Cinalli, Giuseppe, De Antonellis, Pasqualino, Zollo, Massimo, Cooper, Michael, Thompson, Reid, Bailey, Simon, Lindsey, Janet, Di Rocco, Concezio, Massimi, Luca, Michiels, Erna, Scherer, Stephen, Lee, Ji-Yeoun, Cho, Byung-Kyu, Kim, Seung-Ki, Wang, Kyu-Chang, Leonard, Jeffrey, Rubin, Joshua, de Torres, Carmen, Lavarino, Cinzia, Mora, Jaume, Cho, Yoon-Jae, Tabori, Uri, Olson, James, Gajjar, Amar, Packer, Roger, Fan, Xing, Muraszko, Karin, Vibhakar, Rajeev, Eberhart, Charles, Fouladi, Maryam, Lach, Boleslaw, Jung, Shin, Wechsler-Reya, Robert, Fèvre-Montange, Michelle, Jouvet, Anne, Jabado, Nada, Pollack, Ian, Rutkowski, Stefan, Pomeroy, Scott, French, Pim, Kloosterhof, Nanne, Kros, Johan, Van Meir, Erwin, Clifford, Steven, Bourdeaut, Franck, Delattre, Olivier, Doz, François, Hawkins, Cynthia, Malkin, David, Grajkowska, Wieslawa, Perek-Polnik, Marta, Bouffet, Eric, Rutka, James, Pfister, Stefan, Taylor, Michael, Gupta, Nalin, Phillips, Joanna, Weiss, William, and Liau, Linda

Subjects
Adolescent, Biomarkers, Tumor, Child, Child, Preschool, Chromosomes, Human, Pair 11, Chromosomes, Human, Pair 14, Cytogenetics, Female, Gene Expression Profiling, Gene Expression Regulation, Neoplastic, Hedgehog Proteins, Humans, In Situ Hybridization, Fluorescence, Infant, Kruppel-Like Transcription Factors, Male, Medulloblastoma, Nuclear Proteins, Predictive Value of Tests, Prognosis, Proportional Hazards Models, Proto-Oncogene Proteins c-myc, Reproducibility of Results, Risk Assessment, Risk Factors, Tissue Array Analysis, Wnt Proteins, Young Adult, Zinc Finger Protein Gli2
Abstract

PURPOSE: Medulloblastoma comprises four distinct molecular subgroups: WNT, SHH, Group 3, and Group 4. Current medulloblastoma protocols stratify patients based on clinical features: patient age, metastatic stage, extent of resection, and histologic variant. Stark prognostic and genetic differences among the four subgroups suggest that subgroup-specific molecular biomarkers could improve patient prognostication. PATIENTS AND METHODS: Molecular biomarkers were identified from a discovery set of 673 medulloblastomas from 43 cities around the world. Combined risk stratification models were designed based on clinical and cytogenetic biomarkers identified by multivariable Cox proportional hazards analyses. Identified biomarkers were tested using fluorescent in situ hybridization (FISH) on a nonoverlapping medulloblastoma tissue microarray (n = 453), with subsequent validation of the risk stratification models. RESULTS: Subgroup information improves the predictive accuracy of a multivariable survival model compared with clinical biomarkers alone. Most previously published cytogenetic biomarkers are only prognostic within a single medulloblastoma subgroup. Profiling six FISH biomarkers (GLI2, MYC, chromosome 11 [chr11], chr14, 17p, and 17q) on formalin-fixed paraffin-embedded tissues, we can reliably and reproducibly identify very low-risk and very high-risk patients within SHH, Group 3, and Group 4 medulloblastomas. CONCLUSION: Combining subgroup and cytogenetic biomarkers with established clinical biomarkers substantially improves patient prognostication, even in the context of heterogeneous clinical therapies. The prognostic significance of most molecular biomarkers is restricted to a specific subgroup. We have identified a small panel of cytogenetic biomarkers that reliably identifies very high-risk and very low-risk groups of patients, making it an excellent tool for selecting patients for therapy intensification and therapy de-escalation in future clinical trials.

Published
2014

17. TERT promoter mutations are highly recurrent in SHH subgroup medulloblastoma.

Author

Remke, Marc, Ramaswamy, Vijay, Peacock, John, Shih, David, Koelsche, Christian, Northcott, Paul, Hill, Nadia, Cavalli, Florence, Kool, Marcel, Wang, Xin, Mack, Stephen, Barszczyk, Mark, Morrissy, A, Wu, Xiaochong, Agnihotri, Sameer, Luu, Betty, Jones, David, Garzia, Livia, Dubuc, Adrian, Zhukova, Nataliya, Vanner, Robert, Kros, Johan, French, Pim, Van Meir, Erwin, Vibhakar, Rajeev, Zitterbart, Karel, Chan, Jennifer, Bognár, László, Klekner, Almos, Lach, Boleslaw, Jung, Shin, Saad, Ali, Albrecht, Steffen, Zollo, Massimo, Cooper, Michael, Thompson, Reid, Delattre, Oliver, Bourdeaut, Franck, Doz, François, Garami, Miklós, Hauser, Peter, Carlotti, Carlos, Van Meter, Timothy, Massimi, Luca, Fults, Daniel, Pomeroy, Scott, Kumabe, Toshiro, Ra, Young, Leonard, Jeffrey, Elbabaa, Samer, Mora, Jaume, Rubin, Joshua, Cho, Yoon-Jae, McLendon, Roger, Bigner, Darell, Eberhart, Charles, Fouladi, Maryam, Wechsler-Reya, Robert, Faria, Claudia, Croul, Sidney, Huang, Annie, Bouffet, Eric, Hawkins, Cynthia, Dirks, Peter, Schüller, Ulrich, Pollack, Ian, Rutkowski, Stefan, Meyronet, David, Jouvet, Anne, Fèvre-Montange, Michelle, Jabado, Nada, Perek-Polnik, Marta, Grajkowska, Wieslawa, Kim, Seung-Ki, Rutka, James, Malkin, David, Tabori, Uri, Pfister, Stefan, Korshunov, Andrey, von Deimling, Andreas, Taylor, Michael, Weiss, William, and Liau, Linda

Subjects
Adolescent, Adult, Brain Neoplasms, Child, Child, Preschool, DNA Mutational Analysis, Female, Gene Expression Profiling, Genotype, Humans, Infant, Male, Medulloblastoma, Middle Aged, Mutation, Prognosis, Promoter Regions, Genetic, Telomerase
Abstract

Telomerase reverse transcriptase (TERT) promoter mutations were recently shown to drive telomerase activity in various cancer types, including medulloblastoma. However, the clinical and biological implications of TERT mutations in medulloblastoma have not been described. Hence, we sought to describe these mutations and their impact in a subgroup-specific manner. We analyzed the TERT promoter by direct sequencing and genotyping in 466 medulloblastomas. The mutational distributions were determined according to subgroup affiliation, demographics, and clinical, prognostic, and molecular features. Integrated genomics approaches were used to identify specific somatic copy number alterations in TERT promoter-mutated and wild-type tumors. Overall, TERT promoter mutations were identified in 21 % of medulloblastomas. Strikingly, the highest frequencies of TERT mutations were observed in SHH (83 %; 55/66) and WNT (31 %; 4/13) medulloblastomas derived from adult patients. Group 3 and Group 4 harbored this alteration in

Published
2013

18. Recurrent noncoding U1 snRNA mutations drive cryptic splicing in SHH medulloblastoma

Author

Suzuki, Hiromichi, Kumar, Sachin A., Shuai, Shimin, Diaz-Navarro, Ander, Gutierrez-Fernandez, Ana, De Antonellis, Pasqualino, Cavalli, Florence M. G., Juraschka, Kyle, Farooq, Hamza, Shibahara, Ichiyo, Vladoiu, Maria C., Zhang, Jiao, Abeysundara, Namal, Przelicki, David, Skowron, Patryk, Gauer, Nicole, Luu, Betty, Daniels, Craig, Wu, Xiaochong, Forget, Antoine, Momin, Ali, Wang, Jun, Dong, Weifan, Kim, Seung-Ki, Grajkowska, Wieslawa A., Jouvet, Anne, Fèvre-Montange, Michelle, Garrè, Maria Luisa, Nageswara Rao, Amulya A., Giannini, Caterina, Kros, Johan M., French, Pim J., Jabado, Nada, Ng, Ho-Keung, Poon, Wai Sang, Eberhart, Charles G., Pollack, Ian F., Olson, James M., Weiss, William A., Kumabe, Toshihiro, López-Aguilar, Enrique, Lach, Boleslaw, Massimino, Maura, Van Meir, Erwin G., Rubin, Joshua B., Vibhakar, Rajeev, Chambless, Lola B., Kijima, Noriyuki, Klekner, Almos, Bognár, László, Chan, Jennifer A., Faria, Claudia C., Ragoussis, Jiannis, Pfister, Stefan M., Goldenberg, Anna, Wechsler-Reya, Robert J., Bailey, Swneke D., Garzia, Livia, Morrissy, A. Sorana, Marra, Marco A., Huang, Xi, Malkin, David, Ayrault, Olivier, Ramaswamy, Vijay, Puente, Xose S., Calarco, John A., Stein, Lincoln, and Taylor, Michael D.

Published
2019
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19. Subgroup-specific structural variation across 1,000 medulloblastoma genomes.

Author

Northcott, Paul, Shih, David, Peacock, John, Garzia, Livia, Morrissy, A, Zichner, Thomas, Stütz, Adrian, Korshunov, Andrey, Reimand, Jüri, Schumacher, Steven, Beroukhim, Rameen, Ellison, David, Marshall, Christian, Lionel, Anath, Mack, Stephen, Dubuc, Adrian, Yao, Yuan, Ramaswamy, Vijay, Luu, Betty, Rolider, Adi, Cavalli, Florence, Wang, Xin, Remke, Marc, Wu, Xiaochong, Chiu, Readman, Chu, Andy, Chuah, Eric, Corbett, Richard, Hoad, Gemma, Jackman, Shaun, Li, Yisu, Lo, Allan, Mungall, Karen, Nip, Ka, Qian, Jenny, Raymond, Anthony, Thiessen, Nina, Varhol, Richard, Birol, Inanc, Moore, Richard, Mungall, Andrew, Holt, Robert, Kawauchi, Daisuke, Roussel, Martine, Kool, Marcel, Jones, David, Witt, Hendrick, Fernandez-L, Africa, Kenney, Anna, Wechsler-Reya, Robert, Dirks, Peter, Aviv, Tzvi, Grajkowska, Wieslawa, Perek-Polnik, Marta, Haberler, Christine, Delattre, Olivier, Reynaud, Stéphanie, Doz, François, Pernet-Fattet, Sarah, Cho, Byung-Kyu, Kim, Seung-Ki, Wang, Kyu-Chang, Scheurlen, Wolfram, Eberhart, Charles, Fèvre-Montange, Michelle, Jouvet, Anne, Pollack, Ian, Fan, Xing, Muraszko, Karin, Gillespie, G, Di Rocco, Concezio, Massimi, Luca, Michiels, Erna, Kloosterhof, Nanne, French, Pim, Kros, Johan, Olson, James, Ellenbogen, Richard, Zitterbart, Karel, Kren, Leos, Thompson, Reid, Cooper, Michael, Lach, Boleslaw, McLendon, Roger, Bigner, Darell, Fontebasso, Adam, Albrecht, Steffen, Jabado, Nada, Lindsey, Janet, Bailey, Simon, Van Meir, Erwin, Fouladi, Maryam, Nakamura, Hideo, Cinalli, Giuseppe, Garami, Miklós, Hauser, Peter, Saad, Ali, Iolascon, Achille, Jung, Shin, and Carlotti, Carlos

Subjects
Carrier Proteins, Cerebellar Neoplasms, Child, DNA Copy Number Variations, Gene Duplication, Genes, myc, Genome, Human, Genomic Structural Variation, Genomics, Hedgehog Proteins, Humans, Medulloblastoma, NF-kappa B, Nerve Tissue Proteins, Oncogene Proteins, Fusion, Proteins, RNA, Long Noncoding, Signal Transduction, Transforming Growth Factor beta, Translocation, Genetic
Abstract

Medulloblastoma, the most common malignant paediatric brain tumour, is currently treated with nonspecific cytotoxic therapies including surgery, whole-brain radiation, and aggressive chemotherapy. As medulloblastoma exhibits marked intertumoural heterogeneity, with at least four distinct molecular variants, previous attempts to identify targets for therapy have been underpowered because of small samples sizes. Here we report somatic copy number aberrations (SCNAs) in 1,087 unique medulloblastomas. SCNAs are common in medulloblastoma, and are predominantly subgroup-enriched. The most common region of focal copy number gain is a tandem duplication of SNCAIP, a gene associated with Parkinsons disease, which is exquisitely restricted to Group 4α. Recurrent translocations of PVT1, including PVT1-MYC and PVT1-NDRG1, that arise through chromothripsis are restricted to Group 3. Numerous targetable SCNAs, including recurrent events targeting TGF-β signalling in Group 3, and NF-κB signalling in Group 4, suggest future avenues for rational, targeted therapy.

Published
2012

20. Clonal selection drives genetic divergence of metastatic medulloblastoma.

Author

Wu, Xiaochong, Northcott, Paul A, Dubuc, Adrian, Dupuy, Adam J, Shih, David JH, Witt, Hendrik, Croul, Sidney, Bouffet, Eric, Fults, Daniel W, Eberhart, Charles G, Garzia, Livia, Van Meter, Timothy, Zagzag, David, Jabado, Nada, Schwartzentruber, Jeremy, Majewski, Jacek, Scheetz, Todd E, Pfister, Stefan M, Korshunov, Andrey, Li, Xiao-Nan, Scherer, Stephen W, Cho, Yoon-Jae, Akagi, Keiko, MacDonald, Tobey J, Koster, Jan, McCabe, Martin G, Sarver, Aaron L, Collins, V Peter, Weiss, William A, Largaespada, David A, Collier, Lara S, and Taylor, Michael D

Subjects
Animals, Humans, Mice, Medulloblastoma, Neoplasm Metastasis, Li-Fraumeni Syndrome, Disease Models, Animal, DNA Transposable Elements, Survival Rate, Mutagenesis, Insertional, DNA Methylation, CpG Islands, Germ-Line Mutation, Genes, p53, Clonal Evolution, Disease Models, Animal, Genes, p53, Mutagenesis, Insertional, General Science & Technology
Abstract

Medulloblastoma, the most common malignant paediatric brain tumour, arises in the cerebellum and disseminates through the cerebrospinal fluid in the leptomeningeal space to coat the brain and spinal cord. Dissemination, a marker of poor prognosis, is found in up to 40% of children at diagnosis and in most children at the time of recurrence. Affected children therefore are treated with radiation to the entire developing brain and spinal cord, followed by high-dose chemotherapy, with the ensuing deleterious effects on the developing nervous system. The mechanisms of dissemination through the cerebrospinal fluid are poorly studied, and medulloblastoma metastases have been assumed to be biologically similar to the primary tumour. Here we show that in both mouse and human medulloblastoma, the metastases from an individual are extremely similar to each other but are divergent from the matched primary tumour. Clonal genetic events in the metastases can be demonstrated in a restricted subclone of the primary tumour, suggesting that only rare cells within the primary tumour have the ability to metastasize. Failure to account for the bicompartmental nature of metastatic medulloblastoma could be a major barrier to the development of effective targeted therapies.

Published
2012

21. Optimization design of a two-stage multidirectional vibration isolation system for large airborne equipment.

Author

Zhu, Hongyan, Wu, Xiaochong, Lv, Pengzhen, Wang, Yuansheng, Lin, Huagang, Liu, Wei, and Yue, Zhufeng

Subjects
*VIBRATION isolation, *SHOCK absorbers, *ELECTRONIC equipment
Abstract

Purpose: Improvement and optimization design of a two-stage vibration isolation system proposed in this paper are conducted to ensure the device of electronic work effective. Design/methodology/approach: The proposed two-stage vibration isolation system of airborne equipment is optimized and parameterized based on multi-objective genetic algorithm. Findings: The results show that compared with initial two-stage vibration isolation system, the angular vibration of the two-stage vibration isolation system becomes 3.55 × 10-4 rad, which decreases by 89%. The linear isolation effect is improved by at least 67.7%. Originality/value: The optimized two-stage vibration isolation system effectively improves the vibration reduction effect, the resonance peak is obviously improved and the reliability of the mounting bracket and the shock absorber is highly improved, which provides an analysis method for two-stage airborne equipment isolation design under complex dynamic environment. [ABSTRACT FROM AUTHOR]

Published
2024
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22. Therapeutic targeting of ependymoma as informed by oncogenic enhancer profiling

Author

Mack, Stephen C., Pajtler, Kristian W., Chavez, Lukas, Okonechnikov, Konstantin, Bertrand, Kelsey C., Wang, Xiuxing, Erkek, Serap, Federation, Alexander, Song, Anne, Lee, Christine, Wang, Xin, McDonald, Laura, Morrow, James J., Saiakhova, Alina, Sin-Chan, Patrick, Wu, Qiulian, Michaelraj, Kulandaimanuvel Antony, Miller, Tyler E., Hubert, Christopher G., Ryzhova, Marina, Garzia, Livia, Donovan, Laura, Dombrowski, Stephen, Factor, Daniel C., Luu, Betty, Valentim, Claudia L. L., Gimple, Ryan C., Morton, Andrew, Kim, Leo, Prager, Briana C., Lee, John J. Y., Wu, Xiaochong, Zuccaro, Jennifer, Thompson, Yuan, Holgado, Borja L., Reimand, Jri, Ke, Susan Q., Tropper, Adam, Lai, Sisi, Vijayarajah, Senthuran, Doan, Sylvia, Mahadev, Vaidehi, Mian, Ana Fernandez, Grbner, Susanne N., Lienhard, Matthias, Zapatka, Marc, Huang, Zhiqin, Aldape, Kenneth D., Carcaboso, Angel M., Houghton, Peter J., Keir, Stephen T., Milde, Till, Witt, Hendrik, Li, Yan, Li, Chao-Jun, Bian, Xiu-Wu, Jones, David T. W., Scott, Ian, Singh, Sheila K., Huang, Annie, Dirks, Peter B., Bouffet, Eric, Bradner, James E., Ramaswamy, Vijay, Jabado, Nada, Rutka, James T., Northcott, Paul A., Lupien, Mathieu, Lichter, Peter, Korshunov, Andrey, Scacheri, Peter C., Pfister, Stefan M., Kool, Marcel, Taylor, Michael D., and Rich, Jeremy N.

Subjects
Gliomas -- Physiological aspects -- Genetic aspects -- Care and treatment, Cancer genetics -- Research, Cancer research, Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

Author(s): Stephen C. Mack [1, 2, 3, 4]; Kristian W. Pajtler [5, 6, 7]; Lukas Chavez [5, 6, 8]; Konstantin Okonechnikov [5, 6]; Kelsey C. Bertrand [1, 2, 9]; Xiuxing [...]

Published
2018
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23. Supplementary Figures 4-7 from Sleeping Beauty Insertional Mutagenesis Reveals Important Genetic Drivers of Central Nervous System Embryonal Tumors

Author

Beckmann, Pauline J., primary, Larson, Jon D., primary, Larsson, Alex T., primary, Ostergaard, Jason P., primary, Wagner, Sandra, primary, Rahrmann, Eric P., primary, Shamsan, Ghaidan A., primary, Otto, George M., primary, Williams, Rory L., primary, Wang, Jun, primary, Lee, Catherine, primary, Tschida, Barbara R., primary, Das, Paramita, primary, Dubuc, Adrian M., primary, Moriarity, Branden S., primary, Picard, Daniel, primary, Wu, Xiaochong, primary, Rodriguez, Fausto J., primary, Rosemarie, Quincy, primary, Krebs, Ryan D., primary, Molan, Amy M., primary, Demer, Addison M., primary, Frees, Michelle M., primary, Rizzardi, Anthony E., primary, Schmechel, Stephen C., primary, Eberhart, Charles G., primary, Jenkins, Robert B., primary, Wechsler-Reya, Robert J., primary, Odde, David J., primary, Huang, Annie, primary, Taylor, Michael D., primary, Sarver, Aaron L., primary, and Largaespada, David A., primary

Published
2023
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24. Data from Sleeping Beauty Insertional Mutagenesis Reveals Important Genetic Drivers of Central Nervous System Embryonal Tumors

Author

Beckmann, Pauline J., primary, Larson, Jon D., primary, Larsson, Alex T., primary, Ostergaard, Jason P., primary, Wagner, Sandra, primary, Rahrmann, Eric P., primary, Shamsan, Ghaidan A., primary, Otto, George M., primary, Williams, Rory L., primary, Wang, Jun, primary, Lee, Catherine, primary, Tschida, Barbara R., primary, Das, Paramita, primary, Dubuc, Adrian M., primary, Moriarity, Branden S., primary, Picard, Daniel, primary, Wu, Xiaochong, primary, Rodriguez, Fausto J., primary, Rosemarie, Quincy, primary, Krebs, Ryan D., primary, Molan, Amy M., primary, Demer, Addison M., primary, Frees, Michelle M., primary, Rizzardi, Anthony E., primary, Schmechel, Stephen C., primary, Eberhart, Charles G., primary, Jenkins, Robert B., primary, Wechsler-Reya, Robert J., primary, Odde, David J., primary, Huang, Annie, primary, Taylor, Michael D., primary, Sarver, Aaron L., primary, and Largaespada, David A., primary

Published
2023
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25. Supplementary Tables 1-9 from Sleeping Beauty Insertional Mutagenesis Reveals Important Genetic Drivers of Central Nervous System Embryonal Tumors

Author

Beckmann, Pauline J., primary, Larson, Jon D., primary, Larsson, Alex T., primary, Ostergaard, Jason P., primary, Wagner, Sandra, primary, Rahrmann, Eric P., primary, Shamsan, Ghaidan A., primary, Otto, George M., primary, Williams, Rory L., primary, Wang, Jun, primary, Lee, Catherine, primary, Tschida, Barbara R., primary, Das, Paramita, primary, Dubuc, Adrian M., primary, Moriarity, Branden S., primary, Picard, Daniel, primary, Wu, Xiaochong, primary, Rodriguez, Fausto J., primary, Rosemarie, Quincy, primary, Krebs, Ryan D., primary, Molan, Amy M., primary, Demer, Addison M., primary, Frees, Michelle M., primary, Rizzardi, Anthony E., primary, Schmechel, Stephen C., primary, Eberhart, Charles G., primary, Jenkins, Robert B., primary, Wechsler-Reya, Robert J., primary, Odde, David J., primary, Huang, Annie, primary, Taylor, Michael D., primary, Sarver, Aaron L., primary, and Largaespada, David A., primary

Published
2023
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26. Supplementary Figures 1-3 from Sleeping Beauty Insertional Mutagenesis Reveals Important Genetic Drivers of Central Nervous System Embryonal Tumors

Author

Beckmann, Pauline J., primary, Larson, Jon D., primary, Larsson, Alex T., primary, Ostergaard, Jason P., primary, Wagner, Sandra, primary, Rahrmann, Eric P., primary, Shamsan, Ghaidan A., primary, Otto, George M., primary, Williams, Rory L., primary, Wang, Jun, primary, Lee, Catherine, primary, Tschida, Barbara R., primary, Das, Paramita, primary, Dubuc, Adrian M., primary, Moriarity, Branden S., primary, Picard, Daniel, primary, Wu, Xiaochong, primary, Rodriguez, Fausto J., primary, Rosemarie, Quincy, primary, Krebs, Ryan D., primary, Molan, Amy M., primary, Demer, Addison M., primary, Frees, Michelle M., primary, Rizzardi, Anthony E., primary, Schmechel, Stephen C., primary, Eberhart, Charles G., primary, Jenkins, Robert B., primary, Wechsler-Reya, Robert J., primary, Odde, David J., primary, Huang, Annie, primary, Taylor, Michael D., primary, Sarver, Aaron L., primary, and Largaespada, David A., primary

Published
2023
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28. Supplementary Methods and Figure Legends from Foretinib Is Effective Therapy for Metastatic Sonic Hedgehog Medulloblastoma

Author

Faria, Claudia C., primary, Golbourn, Brian J., primary, Dubuc, Adrian M., primary, Remke, Marc, primary, Diaz, Roberto J., primary, Agnihotri, Sameer, primary, Luck, Amanda, primary, Sabha, Nesrin, primary, Olsen, Samantha, primary, Wu, Xiaochong, primary, Garzia, Livia, primary, Ramaswamy, Vijay, primary, Mack, Stephen C., primary, Wang, Xin, primary, Leadley, Michael, primary, Reynaud, Denis, primary, Ermini, Leonardo, primary, Post, Martin, primary, Northcott, Paul A., primary, Pfister, Stefan M., primary, Croul, Sidney E., primary, Kool, Marcel, primary, Korshunov, Andrey, primary, Smith, Christian A., primary, Taylor, Michael D., primary, and Rutka, James T., primary

Published
2023
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29. Data from MyoD Is a Tumor Suppressor Gene in Medulloblastoma

Author

Dey, Joyoti, primary, Dubuc, Adrian M., primary, Pedro, Kyle D., primary, Thirstrup, Derek, primary, Mecham, Brig, primary, Northcott, Paul A., primary, Wu, Xiaochong, primary, Shih, David, primary, Tapscott, Stephen J., primary, LeBlanc, Michael, primary, Taylor, Michael D., primary, and Olson, James M., primary

Published
2023
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32. Supplementary Figure S3 from Foretinib Is Effective Therapy for Metastatic Sonic Hedgehog Medulloblastoma

Author

Faria, Claudia C., primary, Golbourn, Brian J., primary, Dubuc, Adrian M., primary, Remke, Marc, primary, Diaz, Roberto J., primary, Agnihotri, Sameer, primary, Luck, Amanda, primary, Sabha, Nesrin, primary, Olsen, Samantha, primary, Wu, Xiaochong, primary, Garzia, Livia, primary, Ramaswamy, Vijay, primary, Mack, Stephen C., primary, Wang, Xin, primary, Leadley, Michael, primary, Reynaud, Denis, primary, Ermini, Leonardo, primary, Post, Martin, primary, Northcott, Paul A., primary, Pfister, Stefan M., primary, Croul, Sidney E., primary, Kool, Marcel, primary, Korshunov, Andrey, primary, Smith, Christian A., primary, Taylor, Michael D., primary, and Rutka, James T., primary

Published
2023
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33. Data from Foretinib Is Effective Therapy for Metastatic Sonic Hedgehog Medulloblastoma

Author

Faria, Claudia C., primary, Golbourn, Brian J., primary, Dubuc, Adrian M., primary, Remke, Marc, primary, Diaz, Roberto J., primary, Agnihotri, Sameer, primary, Luck, Amanda, primary, Sabha, Nesrin, primary, Olsen, Samantha, primary, Wu, Xiaochong, primary, Garzia, Livia, primary, Ramaswamy, Vijay, primary, Mack, Stephen C., primary, Wang, Xin, primary, Leadley, Michael, primary, Reynaud, Denis, primary, Ermini, Leonardo, primary, Post, Martin, primary, Northcott, Paul A., primary, Pfister, Stefan M., primary, Croul, Sidney E., primary, Kool, Marcel, primary, Korshunov, Andrey, primary, Smith, Christian A., primary, Taylor, Michael D., primary, and Rutka, James T., primary

Published
2023
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39. Supplementary Table S1 from Foretinib Is Effective Therapy for Metastatic Sonic Hedgehog Medulloblastoma

Author

Faria, Claudia C., primary, Golbourn, Brian J., primary, Dubuc, Adrian M., primary, Remke, Marc, primary, Diaz, Roberto J., primary, Agnihotri, Sameer, primary, Luck, Amanda, primary, Sabha, Nesrin, primary, Olsen, Samantha, primary, Wu, Xiaochong, primary, Garzia, Livia, primary, Ramaswamy, Vijay, primary, Mack, Stephen C., primary, Wang, Xin, primary, Leadley, Michael, primary, Reynaud, Denis, primary, Ermini, Leonardo, primary, Post, Martin, primary, Northcott, Paul A., primary, Pfister, Stefan M., primary, Croul, Sidney E., primary, Kool, Marcel, primary, Korshunov, Andrey, primary, Smith, Christian A., primary, Taylor, Michael D., primary, and Rutka, James T., primary

Published
2023
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44. In vivo functional genomics identifies essentiality of potassium homeostasis in medulloblastoma

Author

Fan, Jerry J., primary, Wang, Xin, additional, Erickson, Anders W., additional, Skowron, Patryk, additional, Wang, Xian, additional, Chen, Xin, additional, Shan, Guanqiao, additional, Bahrampour, Shahrzad, additional, Xiong, Yi, additional, Dong, Weifan, additional, Abeysundara, Namal, additional, Francisco, Michelle A., additional, Pusong, Ronwell J., additional, Suárez, Raúl A., additional, Farooq, Hamza, additional, Holgado, Borja L., additional, Wu, Xiaochong, additional, Daniels, Craig, additional, Dupuy, Adam J., additional, Cadiñanos, Juan, additional, Bradley, Allan, additional, Bagchi, Anindya, additional, Moriarity, Branden S., additional, Largaespada, David A., additional, Morrissy, A. Sorana, additional, Ramaswamy, Vijay, additional, Mack, Stephen C., additional, Garzia, Livia, additional, Dirks, Peter B., additional, Wanggou, Siyi, additional, Li, Xuejun, additional, Sun, Yu, additional, Taylor, Michael D., additional, and Huang, Xi, additional

Published
2022
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45. Medulloblastoma subgroups remain stable across primary and metastatic compartments

Author

Wang, Xin, Dubuc, Adrian M., Ramaswamy, Vijay, Mack, Stephen, Gendoo, Deena M. A., Remke, Marc, Wu, Xiaochong, Garzia, Livia, Luu, Betty, Cavalli, Florence, Peacock, John, López, Borja, Skowron, Patryk, Zagzag, David, Lyden, David, Hoffman, Caitlin, Cho, Yoon-Jae, Eberhart, Charles, MacDonald, Tobey, Li, Xiao-Nan, Van Meter, Timothy, Northcott, Paul A., Haibe-Kains, Benjamin, Hawkins, Cynthia, Rutka, James T., Bouffet, Eric, Pfister, Stefan M., Korshunov, Andrey, and Taylor, Michael D.

Published
2015
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47. The G protein α subunit G[α.sub.s] is a tumor suppressor in Sonic hedgehog-driven medulloblastoma

Author

He, Xuelian, Zhang, Liguo, Chen, Ying, Remke, Marc, Shih, David, Lu, Fanghui, Wang, Haibo, Deng, Yaqi, Yu, Yang, Xia, Yong, Wu, Xiaochong, Ramaswamy, Vijay, Hu, Tom, Wang, Fan, Zhou, Wenhao, Burns, Dennis K., Kim, Se Hoon, Kool, Marcel, Pfister, Stefan M., Weinstein, Lee S., Pomeroy, Scott L., Gilbertson, Richard J., Rubin, Joshua B., Hou, Yiping, Wechsler-Reya, Robert, Taylor, Michael D., and Lu, Q.Richard

Subjects
Medulloblastoma -- Development and progression -- Research -- Analysis, G proteins -- Research -- Analysis -- Physiological aspects, Biological sciences, Health
Abstract

Medulloblastoma, the most common malignant childhood brain tumor, exhibits distinct molecular subtypes and cellular origins. Genetic alterations driving medulloblastoma initiation and progression remain poorly understood. Herein, we identify GNAS, encoding the G protein G[α.sub.s], as a potent tumor suppressor gene that, when expressed at low levels, defines a subset of aggressive Sonic hedgehog (SHH)-driven human medulloblastomas. Ablation of the single Gnas gene in anatomically distinct progenitors in mice is sufficient to induce Shh-associated medulloblastomas, which recapitulate their human counterparts. G[α.sub.s] is highly enriched at the primary cilium of granule neuron precursors and suppresses Shh signaling by regulating both the cAMP-dependent pathway and ciliary trafficking of Hedgehog pathway components. Elevation in levels of a G[α.sub.s] effector, cAMP, effectively inhibits tumor cell proliferation and progression in Gnas-ablated mice. Thus, our gain- and loss-of-function studies identify a previously unrecognized tumor suppressor function for G[α.sub.s] that can be found consistently across Shh-group medulloblastomas of disparate cellular and anatomical origins, highlighting G protein modulation as a potential therapeutic avenue., Medulloblastoma (MB) comprises clinically and molecularly distinct tumors that arise either in the cerebellum or brainstem (1-3). Although current treatments improve survival rates, patients suffer severe side effects and relapse [...]

Published
2014
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48. Locoregional delivery of CAR T cells to the cerebrospinal fluid for treatment of metastatic medulloblastoma and ependymoma

Author

Donovan, Laura K, Delaidelli, Alberto, Joseph, Sujith K, Bielamowicz, Kevin, Fousek, Kristen, Holgado, Borja L, Manno, Alex, Srikanthan, Dilakshan, Gad, Ahmed Z, Van Ommeren, Randy, Przelicki, David, Richman, Cory, Ramaswamy, Vijay, Daniels, Craig, Pallota, Jonelle G, Douglas, Tajana, Joynt, Alyssa C M, Haapasalo, Joonas, Nor, Carolina, Vladoiu, Maria C, Kuzan-Fischer, Claudia M, Garzia, Livia, Mack, Stephen C, Varadharajan, Srinidhi, Baker, Matthew L, Hendrikse, Liam, Ly, Michelle, Kharas, Kaitlin, Balin, Polina, Wu, Xiaochong, Qin, Lei, Huang, Ning, Guerreiro Stücklin, Ana, et al, and University of Zurich

Subjects
10036 Medical Clinic, 1300 General Biochemistry, Genetics and Molecular Biology, 610 Medicine & health
Published
2020

49. Metabolic Regulation of the Epigenome Drives Lethal Infantile Ependymoma

Author

Michealraj, Kulandaimanuvel Antony, primary, Kumar, Sachin A., additional, Kim, Leo J.Y., additional, Cavalli, Florence M.G., additional, Przelicki, David, additional, Wojcik, John B., additional, Delaidelli, Alberto, additional, Bajic, Andrea, additional, Saulnier, Olivier, additional, MacLeod, Graham, additional, Vellanki, Ravi N., additional, Vladoiu, Maria C., additional, Guilhamon, Paul, additional, Ong, Winnie, additional, Lee, John J.Y., additional, Jiang, Yanqing, additional, Holgado, Borja L., additional, Rasnitsyn, Alex, additional, Malik, Ahmad A., additional, Tsai, Ricky, additional, Richman, Cory M., additional, Juraschka, Kyle, additional, Haapasalo, Joonas, additional, Wang, Evan Y., additional, De Antonellis, Pasqualino, additional, Suzuki, Hiromichi, additional, Farooq, Hamza, additional, Balin, Polina, additional, Kharas, Kaitlin, additional, Van Ommeren, Randy, additional, Sirbu, Olga, additional, Rastan, Avesta, additional, Krumholtz, Stacey L., additional, Ly, Michelle, additional, Ahmadi, Moloud, additional, Deblois, Geneviève, additional, Srikanthan, Dilakshan, additional, Luu, Betty, additional, Loukides, James, additional, Wu, Xiaochong, additional, Garzia, Livia, additional, Ramaswamy, Vijay, additional, Kanshin, Evgeny, additional, Sánchez-Osuna, María, additional, El-Hamamy, Ibrahim, additional, Coutinho, Fiona J., additional, Prinos, Panagiotis, additional, Singh, Sheila, additional, Donovan, Laura K., additional, Daniels, Craig, additional, Schramek, Daniel, additional, Tyers, Mike, additional, Weiss, Samuel, additional, Stein, Lincoln D., additional, Lupien, Mathieu, additional, Wouters, Bradly G., additional, Garcia, Benjamin A., additional, Arrowsmith, Cheryl H., additional, Sorensen, Poul H., additional, Angers, Stephane, additional, Jabado, Nada, additional, Dirks, Peter B., additional, Mack, Stephen C., additional, Agnihotri, Sameer, additional, Rich, Jeremy N., additional, and Taylor, Michael D., additional

Published
2020
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