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1. A group 3 medulloblastoma stem cell program is maintained by OTX2-mediated alternative splicing

Author

Saulnier, Olivier, Zagozewski, Jamie, Liang, Lisa, Hendrikse, Liam D., Layug, Paul, Gordon, Victor, Aldinger, Kimberly A., Haldipur, Parthiv, Borlase, Stephanie, Coudière-Morrison, Ludivine, Cai, Ting, Martell, Emma, Gonzales, Naomi M., Palidwor, Gareth, Porter, Christopher J., Richard, Stéphane, Sharif, Tanveer, Millen, Kathleen J., Doble, Brad W., Taylor, Michael D., and Werbowetski-Ogilvie, Tamra E.

Published
2024
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6. 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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7. Combined MEK and JAK/STAT3 pathway inhibition effectively decreases SHH medulloblastoma tumor progression

Author

Zagozewski, Jamie, Borlase, Stephanie, Guppy, Brent J., Coudière-Morrison, Ludivine, Shahriary, Ghazaleh M., Gordon, Victor, Liang, Lisa, Cheng, Stephen, Porter, Christopher J., Kelley, Rhonda, Hawkins, Cynthia, Chan, Jennifer A., Liang, Yan, Gong, Jingjing, Nör, Carolina, Saulnier, Olivier, Wechsler-Reya, Robert J., Ramaswamy, Vijay, and Werbowetski-Ogilvie, Tamra E.

Published
2022
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8. 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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9. Slit

Author

Werbowetski-Ogilvie, Tamra E., Sadr, Mohamad Seyed, Del Maestro, Rolando F., and Schwab, Manfred, editor

Published
2017
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12. An OTX2-PAX3 signaling axis regulates Group 3 medulloblastoma cell fate

Author

Zagozewski, Jamie, Shahriary, Ghazaleh M., Morrison, Ludivine Coudière, Saulnier, Olivier, Stromecki, Margaret, Fresnoza, Agnes, Palidwor, Gareth, Porter, Christopher J., Forget, Antoine, Ayrault, Olivier, Hawkins, Cynthia, Chan, Jennifer A., Vladoiu, Maria C., Sundaresan, Lakshmikirupa, Arsenio, Janilyn, Taylor, Michael D., Ramaswamy, Vijay, and Werbowetski-Ogilvie, Tamra E.

Published
2020
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14. Slit

Author

Werbowetski-Ogilvie, Tamra E., Del Maestro, Rolando F., Sadr, Mohamad Seyed, and Schwab, Manfred, editor

Published
2011
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17. Slit

Author

Werbowetski-Ogilvie, Tamra E., Sadr, Mohamad Seyed, Del Maestro, Rolando F., and Schwab, Manfred, editor

Published
2009
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18. Slit

Author

Werbowetski-Ogilvie, Tamra E., primary, Sadr, Mohamad Seyed, additional, and Del Maestro, Rolando F., additional

Published
2015
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20. SNO 2020 diversity survey: defining demographics, racial biases, career success metrics and a path forward for the field of neuro-oncology

Author

Chukwueke, Ugonma N, primary, Vera, Elizabeth, additional, Acquaye, Alvina, additional, Hervey-Jumper, Shawn L, additional, Odia, Yazmin, additional, Klesse, Laura J, additional, Dunbar, Erin, additional, Sharma, Akanksha, additional, Fonkem, Ekokobe, additional, Thomas, Alissa A, additional, Werbowetski-Ogilvie, Tamra E, additional, Camelo-Piragua, Sandra, additional, Gatson, Na Tosha N, additional, de la Fuente, Macarena I, additional, Armstrong, Terri S, additional, Porter, Alyx B, additional, and Jackson, Sadhana, additional

Published
2021
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23. CD271+ Cells Are Diagnostic and Prognostic and Exhibit Elevated MAPK Activity in SHH Medulloblastoma

Author

Liang, Lisa, primary, Coudière-Morrison, Ludivine, additional, Tatari, Nazanin, additional, Stromecki, Margaret, additional, Fresnoza, Agnes, additional, Porter, Christopher J., additional, Del Bigio, Marc R., additional, Hawkins, Cynthia, additional, Chan, Jennifer A., additional, Ryken, Timothy C., additional, Taylor, Michael D., additional, Ramaswamy, Vijay, additional, and Werbowetski-Ogilvie, Tamra E., additional

Published
2018
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24. Characterization of a novel OTX2-driven stem cell program in Group 3 and Group 4 medulloblastoma

Author

Stromecki, Margaret, primary, Tatari, Nazanin, additional, Morrison, Ludivine Coudière, additional, Kaur, Ravinder, additional, Zagozewski, Jamie, additional, Palidwor, Gareth, additional, Ramaswamy, Vijay, additional, Skowron, Patryk, additional, Wölfl, Matthias, additional, Milde, Till, additional, Del Bigio, Marc R., additional, Taylor, Michael D., additional, and Werbowetski-Ogilvie, Tamra E., additional

Published
2018
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26. Characterization of novel biomarkers in selecting for subtype specific medulloblastoma phenotypes

Author

Liang, Lisa, primary, Aiken, Christopher, additional, McClelland, Robyn, additional, Morrison, Ludivine Coudière, additional, Tatari, Nazanin, additional, Remke, Marc, additional, Ramaswamy, Vijay, additional, Issaivanan, Magimairajan, additional, Ryken, Timothy, additional, Del Bigio, Marc R., additional, Taylor, Michael D., additional, and Werbowetski-Ogilvie, Tamra E., additional

Published
2015
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27. Slit

Author

Werbowetski-Ogilvie, Tamra E., primary, Sadr, Mohamad Seyed, additional, and Del Maestro, Rolando F., additional

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28. Differential cellular responses induced by dorsomorphin and LDN-193189 in chemotherapy-sensitive and chemotherapy-resistant human epithelial ovarian cancer cells

Author

Ali, Jennifer L., primary, Lagasse, Brittany J., additional, Minuk, Ainsley J., additional, Love, Allison J., additional, Moraya, Amani I., additional, Lam, Linda, additional, Arthur, Gilbert, additional, Gibson, Spencer B., additional, Morrison, Ludivine Coudière, additional, Werbowetski-Ogilvie, Tamra E., additional, Fu, Yangxin, additional, and Nachtigal, Mark W., additional

Published
2014
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32. Characterization of human embryonic stem cells with features of neoplastic progression

Author

Werbowetski-Ogilvie, Tamra E, primary, Bossé, Marc, additional, Stewart, Morag, additional, Schnerch, Angelique, additional, Ramos-Mejia, Veronica, additional, Rouleau, Anne, additional, Wynder, Tracy, additional, Smith, Mary-Jo, additional, Dingwall, Steve, additional, Carter, Tim, additional, Williams, Christopher, additional, Harris, Charles, additional, Dolling, Joanna, additional, Wynder, Christopher, additional, Boreham, Doug, additional, and Bhatia, Mickie, additional

Published
2009
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34. Deconstruction of Medulloblastoma Cellular Heterogeneity Reveals Differences between the Most Highly Invasive and Self-Renewing Phenotypes.

Author

Morrison, Ludivine Coudière, McClelland, Robyn, Aiken, Christopher, Bridges, Melissa, Liang, Lisa, Xin Wang, Di Curzio, Domenico, Bigio, Marc R. Del, Taylor, Michael D., and Werbowetski-Ogilvie, Tamra E.

Subjects
*MEDULLOBLASTOMA, *BRAIN tumors, *GENE expression, *CANCER cells, *NEUROTROPHIN receptors
Abstract

Medulloblastoma (MB) is the most common malignant primary pediatric brain tumor. Major research efforts have focused on characterizing and targeting putative brain tumor stem or propagating cell populations from the tumor mass. However, less is known about the relationship between these cells and highly invasive MB cells that evade current therapies. Here, we dissected MB cellular heterogeneity and directly compared invasion and self-renewal. Analysis of higher versus lower self-renewing tumor spheres and stationary versus migrating adherent MB cells revealed differential expression of the cell surface markers CD271 [p75 neurotrophin receptor (p75NTR)] and CD133. Cell sorting demonstrated that CD271 selects for subpopulations with a higher capacity for self-renewal, whereas CD133 selects for cells exhibiting increased invasion in vitro. CD271 expression is higher in human fetal cerebellum and primary samples of the Shh MB molecular variant and lower in the more aggressive, invasive group 3 and 4 subgroups. Global gene expression analysis of higher versus lower self-renewing MB tumor spheres revealed down-regulation of a cell movement transcription program in the higher self-renewing state and a novel potential role for axon guidance signaling in MB-propagating cells. We have identified a cell surface signature based on CD133/CD271 expression that selects for MB cells with a higher self-renewal potential or invasive capacity in vitro. Our study underscores a previously unappreciated role for CD271 in selecting for MB cell phenotypes and suggests that successful treatment of pediatric brain tumors requires concomitant targeting of a spectrum of transitioning self-renewing and highly infiltrative cell subpopulations. [ABSTRACT FROM AUTHOR]

Published
2013
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35. From sorting to sequencing in the molecular era: the evolution of the cancer stem cell model in medulloblastoma.

Author

Werbowetski-Ogilvie TE

Subjects
Cell Movement, Child, Humans, Neoplastic Stem Cells pathology, Transcriptome, Cerebellar Neoplasms genetics, Cerebellar Neoplasms metabolism, Cerebellar Neoplasms pathology, Medulloblastoma genetics, Medulloblastoma metabolism, Medulloblastoma pathology
Abstract

The cancer stem cell (CSC) model posits that tumors contain subpopulations that display defining features of normal stem cells including self-renewal capacity and differentiation. Tumor cells exhibiting these features are now considered to be responsible for tumor propagation and drug resistance in a wide variety of cancers. Therefore, the identification of robust CSC markers and characterization of CSC-specific molecular signatures may lead to the identification of novel therapeutics that selectively abolish this clinically relevant cell population while preserving normal tissue. Brain tumor researchers have been at the forefront of the CSC field. From initial in vitro cell sorting experiments to the sophisticated bioinformatic technologies that now exquisitely resolve primary brain tumors at a single-cell level, recent glioma and medulloblastoma (MB) studies have integrated developmental state with genomic and transcriptome data to identify the spectrum of cell types that may drive tumor progression. This review will examine the last two decades of CSC studies in the field. Seminal discoveries, emerging controversies, and outstanding questions will be covered with a particular focus on MB, the most common malignant primary brain tumor in children., (© 2021 Federation of European Biochemical Societies.)

Published
2022
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36. Embryonic Stem Cell Models of Human Brain Tumors.

Author

Morrison LC, Tatari N, and Werbowetski-Ogilvie TE

Subjects
Animals, Cattle, Cell Migration Assays, Humans, Lentivirus metabolism, Mice, Neural Stem Cells pathology, Neural Stem Cells transplantation, Perfusion, Spheroids, Cellular pathology, Tissue Fixation, Transduction, Genetic, Brain Neoplasms pathology, Human Embryonic Stem Cells pathology, Models, Biological
Abstract

Utilization of human embryonic stem cells (hESCs) as a model system to study highly malignant pediatric cancers has led to significant insight into the molecular mechanisms governing tumor progression and has revealed novel therapeutic targets for these devastating diseases. Here, we describe a method for generating heterogeneous populations of neural precursors from both normal and neoplastic hESCs and the subsequent injection of neoplastic human embryonic neural cells (hENs) into intracerebellar or intracranial xenograft models. Histopathologically, neural tumors derived from neoplastic hENs exhibit features similar to more aggressive medulloblastoma, the most common malignant primary pediatric brain tumor. In this chapter, we will outline the detailed methods for culturing normal and neoplastic neural precursor cells in both adherent and tumorsphere format and the full characterization of the brain tumors generated from these cells in non-obese diabetic severe combined immunodeficiency (NOD SCID) mice.

Published
2019
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37. CD271 + Cells Are Diagnostic and Prognostic and Exhibit Elevated MAPK Activity in SHH Medulloblastoma.

Author

Liang L, Coudière-Morrison L, Tatari N, Stromecki M, Fresnoza A, Porter CJ, Del Bigio MR, Hawkins C, Chan JA, Ryken TC, Taylor MD, Ramaswamy V, and Werbowetski-Ogilvie TE

Subjects
Anilides administration & dosage, Annexin A5 genetics, Cell Movement genetics, Cell Proliferation genetics, Cell Survival drug effects, Child, Enzyme Inhibitors administration & dosage, Female, Gene Expression Regulation, Neoplastic, High-Throughput Nucleotide Sequencing, Humans, Kaplan-Meier Estimate, MAP Kinase Kinase Kinase 1 antagonists & inhibitors, Magnetic Resonance Angiography, Male, Medulloblastoma drug therapy, Medulloblastoma pathology, Pyridines administration & dosage, Biomarkers, Tumor genetics, Medulloblastoma genetics, Nerve Tissue Proteins genetics, Prognosis, Receptors, Nerve Growth Factor genetics
Abstract

The extensive heterogeneity both between and within the medulloblastoma subgroups underscores a critical need for variant-specific biomarkers and therapeutic strategies. We previously identified a role for the CD271/p75 neurotrophin receptor (p75NTR) in regulating stem/progenitor cells in the SHH medulloblastoma subgroup. Here, we demonstrate the utility of CD271 as a novel diagnostic and prognostic marker for SHH medulloblastoma using IHC analysis and transcriptome data across 763 primary tumors. RNA sequencing of CD271 + and CD271 - cells revealed molecularly distinct, coexisting cellular subsets, both in vitro and in vivo MAPK/ERK signaling was upregulated in the CD271 + population, and inhibiting this pathway reduced endogenous CD271 levels, stem/progenitor cell proliferation, and cell survival as well as cell migration in vitro Treatment with the MEK inhibitor selumetinib extended survival and reduced CD271 levels in vivo , whereas, treatment with vismodegib, a well-known smoothened (SMO) inhibitor currently in clinical trials for the treatment of recurrent SHH medulloblastoma, had no significant effect in our models. Our study demonstrates the clinical utility of CD271 as both a diagnostic and prognostic tool for SHH medulloblastoma tumors and reveals a novel role for MEK inhibitors in targeting CD271 + SHH medulloblastoma cells. Significance: This study identifies CD271 as a specific and novel biomarker of SHH-type medulloblastoma and that targeting CD271 + cells through MEK inhibition represents a novel therapeutic strategy for the treatment of SHH medulloblastoma. Cancer Res; 78(16); 4745-59. ©2018 AACR ., (©2018 American Association for Cancer Research.)

Published
2018
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38. Isolation of a natural inhibitor of human malignant glial cell invasion: inter alpha-trypsin inhibitor heavy chain 2.

Author

Werbowetski-Ogilvie TE, Agar NY, Waldkircher de Oliveira RM, Faury D, Antel JP, Jabado N, and Del Maestro RF

Subjects
Alpha-Globulins genetics, Alpha-Globulins metabolism, Alpha-Globulins physiology, Animals, Blotting, Western, Brain Neoplasms metabolism, Brain Neoplasms pathology, Cell Adhesion physiology, Cell Movement physiology, Down-Regulation, Glioma metabolism, Glioma pathology, Humans, Immunohistochemistry, Membrane Glycoproteins biosynthesis, Membrane Glycoproteins genetics, Mice, Neoplasm Invasiveness, Phosphorylation, Proto-Oncogene Proteins c-akt metabolism, RNA, Messenger biosynthesis, RNA, Messenger genetics, Recombinant Fusion Proteins biosynthesis, Recombinant Fusion Proteins genetics, Trypsin Inhibitor, Kunitz Soybean biosynthesis, Trypsin Inhibitor, Kunitz Soybean genetics, Alpha-Globulins isolation & purification, Brain Neoplasms chemistry, Glioma chemistry
Abstract

Malignant central nervous system (CNS) tumors, such as glioblastoma multiforme, invade the brain and disrupt normal tissue architecture, making complete surgical removal virtually impossible. Here, we have developed and optimized a purification strategy to isolate and identify natural inhibitors of glioma cell invasion in a three-dimensional collagen type I matrix. Inter alpha-trypsin inhibitor heavy chain 2 (ITI H2) was identified from the most inhibitory fractions and its presence was confirmed both as a single protein and in a bikunin-bound form. Stable overexpression in U251 glioma cells validated ITI H2's strong inhibition of human glioma cell invasion together with significant inhibition of cell proliferation and promotion of cell-cell adhesion. Analysis of primary human brain tumors showed significantly higher levels of ITI H2 in normal brain and low-grade tumors compared with high-grade gliomas, indicating an inverse correlation with malignancy. The phosphatidylinositol 3-kinase/Akt signaling cascade seemed to be one of the pathways involved in the effect of ITI H2 on U251 cells. These findings suggest that reduction of ITI H2 expression correlates with brain tumor progression and that targeting factors responsible for its loss or restoring the ITI supply exogenously may serve as potential therapeutic strategies for a variety of CNS tumors.

Published
2006
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