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5 results on '"John J. Y. Lee"'

1. The transcriptional landscape of Shh medulloblastoma

Author

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

Subjects
Science
Abstract

Sonic Hedgehog medulloblastoma (Shh-MB) comprises four subtypes each with distinct clinical traits. Here the authors characterize the genome, transcriptome, and methylome of Shh-MB subtypes, revealing a complex fusion landscape and the molecular convergence of MYCN and cAMP signaling pathways.

Published
2021
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2. Lactobacillus salivarius HHuMin-U Activates Innate Immune Defense against Norovirus Infection through TBK1-IRF3 and NF-κB Signaling Pathways

Author

Da Hyun Kim, Minju Jeong, Jae Hwan Kim, Joe Eun Son, John J. Y. Lee, Sang-jun Park, Juyeon Lee, Minwoo Kim, Jong-Won Oh, Myeong Soo Park, and Sanguine Byun

Subjects
Science
Abstract

The composition of commensal bacteria plays a critical role in controlling immune responses in the intestine. Studies have shown that specific bacterial strains may have the capacity to enhance host immune defense against gastrointestinal viral infections. While norovirus is known to be the most common cause of gastroenteritis, leading to an estimated 200,000 deaths every year, identification of bacterial strains with protective effects against norovirus infection remains elusive. Here, we discovered Lactobacillus salivarius HHuMin-U (HHuMin-U) as a potent antiviral strain against norovirus infection. HHuMin-U significantly suppressed murine norovirus replication and lowered viral RNA titers in macrophages. The transcriptome sequencing (RNA sequencing) analysis revealed that HHuMin-U markedly enhanced the expression level of antiviral interferon-stimulated genes compared to mock treatment. HHuMin-U treatment dose-dependently induced type I interferons (IFN-α and IFN-β) and tumor necrosis factor-α production in mouse and human macrophages, promoting antiviral innate responses against norovirus infection. Investigation on the molecular mechanism demonstrated that HHuMin-U can activate nuclear factor κB and TANK-binding kinase 1 (TBK1)–interferon regulatory factor 3 signaling pathways, leading to the phosphorylation of signal transducer and activator of transcription 1 and signal transducer and activator of transcription 2, the key mediators of interferon-stimulated genes. Finally, oral administration of HHuMin-U increased IFN-β levels in the ileum of mice and altered the gut microbiome profile. These results suggest the species/strain-specific importance of gut microbial composition for antiviral immune responses and the potential use of HHuMin-U as a probiotic agent.

Published
2022
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3. Failure of human rhombic lip differentiation underlies medulloblastoma formation

Author

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

Subjects
Histone Demethylases, Otx Transcription Factors, Multidisciplinary, Core Binding Factor alpha Subunits, Muscle Proteins, Cell Differentiation, Article, Metencephalon, Repressor Proteins, Ki-67 Antigen, Cerebellum, Mutation, Humans, Cell Lineage, Hedgehog Proteins, Cerebellar Neoplasms, T-Box Domain Proteins, Medulloblastoma, Transcription Factors
Abstract

Medulloblastoma (MB) comprises a group of heterogeneous paediatric embryonal neoplasms of the hindbrain with strong links to early development of the hindbrain 1–4. Mutations that activate Sonic hedgehog signalling lead to Sonic hedgehog MB in the upper rhombic lip (RL) granule cell lineage 5–8. By contrast, mutations that activate WNT signalling lead to WNT MB in the lower RL 9,10. However, little is known about the more commonly occurring group 4 (G4) MB, which is thought to arise in the unipolar brush cell lineage 3,4. Here we demonstrate that somatic mutations that cause G4 MB converge on the core binding factor alpha (CBFA) complex and mutually exclusive alterations that affect CBFA2T2, CBFA2T3, PRDM6, UTX and OTX2. CBFA2T2 is expressed early in the progenitor cells of the cerebellar RL subventricular zone in Homo sapiens, and G4 MB transcriptionally resembles these progenitors but are stalled in developmental time. Knockdown of OTX2 in model systems relieves this differentiation blockade, which allows MB cells to spontaneously proceed along normal developmental differentiation trajectories. The specific nature of the split human RL, which is destined to generate most of the neurons in the human brain, and its high level of susceptible EOMES +KI67 + unipolar brush cell progenitor cells probably predisposes our species to the development of G4 MB.

Published
2022

4. Author Correction: Failure of human rhombic lip differentiation underlies medulloblastoma formation

Author

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

Subjects
Multidisciplinary
Published
2022

5. EPCO-38. TYPE B ULTRA LONG-RANGE INTERACTIONS IN PFAS (TULIPS) ARE RECURRENT EPIGENOMIC FEATURES OF PFA EPENDYMOMA

Author

Michael Johnston, John J Y Lee, Bo Hu, Ana Nikolic, Audrey Baguette, Seungil Paik, Haifen Chen, Sachin Kumar, Carol Chen, Selin Jessa, Polina Balin, Vernon Fong, Melissa Zwaig, Kulandaimanuvel MichealRaj, Xun Chen, Yanlin Zhang, Srinidhi Varadharajan, Pierre Billon, Nikoleta Juretic, Craig Daniels, Caterina Giannini, Eric Thompson, Peter Hauser, Seung-Ki Kim, Kyu-Chang Wang, Ji Yeoun Lee, Wieslawa Grajkowska, Sameer Agnihotri, Stephen C Mack, Benjamin Ellezam, Alex Weil, Guillaume Bourque, Jennifer Chan, Mathieu Lupien, Jiannis Ragoussis, Claudia Kleinman, Jacek Majewski, Nada Jabado, Michael Taylor, Mathieu Blanchette, and Marco Gallo

Subjects
Cancer Research, Oncology, Neurology (clinical)
Abstract

Posterior Fossa Group A (PFA) ependymomas are pediatric brain tumors with extremely poor survival outcomes. As protein-coding mutations in PFA are exceedingly rare, the underlying etiology of these tumors remains elusive. Elevated CpG island methylation and depletion of H3K27me3 have been described in PFA, leading to the hypothesis that PFA may be driven by a dysregulated epigenetic state. In this study, we sought to determine how three-dimensional (3D) genome features (such as DNA loops, domains, and compartments) differ between pediatric brain tumors. We performed Hi-C sequencing on a collection of 64 patient specimens and patient-derived primary cultures that collectively span multiple subgroups of ependymoma, medulloblastoma, high-grade glioma, and non-neoplastic brain. For certain samples, we further performed RNA-seq, histone modification ChIP-seq, or whole-genome bisulfite sequencing to allow multiomic data integration. Overall, the 3D genome organization of PFA samples appeared distinct from other tumor types. We identified and defined TULIPs: a subset of type B compartments, separated by genomic distances greater than 10 Mbp, that exhibit a striking fivefold increase in reciprocal interaction strength. These TULIPs recurred at the same genomic positions across the vast majority of PFA samples with minimal representation among other tumor or non-tumor samples. TULIPs displayed enrichment for heterochromatic features such as H3K9me3 and late replication timing and were depleted of euchromatic features such as H3K27ac and protein-coding genes. By using immuno-fluorescence for H3K9me3 and oligo-FISH to label TULIP regions, we demonstrated that TULIP regions are more compact in PFA than other tumors. Finally, by applying inhibitors of H3K9 lysine methylation to PFA cultures we showed that TULIPs become more diffuse and cell viability is reduced. Altogether, this work defines TULIPs as highly recurrent epigenetic features of PFA tumors.

Published
2022

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