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3 results on '"Gabrielle Gionet"'

1. PPM1D mutations are oncogenic drivers of de novo diffuse midline glioma formation

Author

Prasidda Khadka, Zachary J. Reitman, Sophie Lu, Graham Buchan, Gabrielle Gionet, Frank Dubois, Diana M. Carvalho, Juliann Shih, Shu Zhang, Noah F. Greenwald, Travis Zack, Ofer Shapira, Kristine Pelton, Rachel Hartley, Heather Bear, Yohanna Georgis, Spandana Jarmale, Randy Melanson, Kevin Bonanno, Kathleen Schoolcraft, Peter G. Miller, Alexandra L. Condurat, Elizabeth M. Gonzalez, Kenin Qian, Eric Morin, Jaldeep Langhnoja, Leslie E. Lupien, Veronica Rendo, Jeromy Digiacomo, Dayle Wang, Kevin Zhou, Rushil Kumbhani, Maria E. Guerra Garcia, Claire E. Sinai, Sarah Becker, Rachel Schneider, Jayne Vogelzang, Karsten Krug, Amy Goodale, Tanaz Abid, Zohra Kalani, Federica Piccioni, Rameen Beroukhim, Nicole S. Persky, David E. Root, Angel M. Carcaboso, Benjamin L. Ebert, Christine Fuller, Ozgun Babur, Mark W. Kieran, Chris Jones, Hasmik Keshishian, Keith L. Ligon, Steven A. Carr, Timothy N. Phoenix, and Pratiti Bandopadhayay

Subjects
Science
Abstract

Abstract The role of PPM1D mutations in de novo gliomagenesis has not been systematically explored. Here we analyze whole genome sequences of 170 pediatric high-grade gliomas and find that truncating mutations in PPM1D that increase the stability of its phosphatase are clonal driver events in 11% of Diffuse Midline Gliomas (DMGs) and are enriched in primary pontine tumors. Through the development of DMG mouse models, we show that PPM1D mutations potentiate gliomagenesis and that PPM1D phosphatase activity is required for in vivo oncogenesis. Finally, we apply integrative phosphoproteomic and functional genomics assays and find that oncogenic effects of PPM1D truncation converge on regulators of cell cycle, DNA damage response, and p53 pathways, revealing therapeutic vulnerabilities including MDM2 inhibition.

Published
2022
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2. Neuronal differentiation and cell-cycle programs mediate response to BET-bromodomain inhibition in MYC-driven medulloblastoma

Author

Pratiti Bandopadhayay, Federica Piccioni, Ryan O’Rourke, Patricia Ho, Elizabeth M. Gonzalez, Graham Buchan, Kenin Qian, Gabrielle Gionet, Emily Girard, Margo Coxon, Matthew G. Rees, Lisa Brenan, Frank Dubois, Ofer Shapira, Noah F. Greenwald, Melanie Pages, Amanda Balboni Iniguez, Brenton R. Paolella, Alice Meng, Claire Sinai, Giovanni Roti, Neekesh V. Dharia, Amanda Creech, Benjamin Tanenbaum, Prasidda Khadka, Adam Tracy, Hong L. Tiv, Andrew L. Hong, Shannon Coy, Rumana Rashid, Jia-Ren Lin, Glenn S. Cowley, Fred C. Lam, Amy Goodale, Yenarae Lee, Kathleen Schoolcraft, Francisca Vazquez, William C. Hahn, Aviad Tsherniak, James E. Bradner, Michael B. Yaffe, Till Milde, Stefan M. Pfister, Jun Qi, Monica Schenone, Steven A. Carr, Keith L. Ligon, Mark W. Kieran, Sandro Santagata, James M. Olson, Prafulla C. Gokhale, Jacob D. Jaffe, David E. Root, Kimberly Stegmaier, Cory M. Johannessen, and Rameen Beroukhim

Subjects
Science
Abstract

BET-bromodomain inhibitors could be used to treat medulloblastoma tumors with Myc amplifications. Here, the authors show that both the response and resistance to BET inhibitors in mice is mediated by bHLH/homeobox transcription factors.

Published
2019
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3. The Origins and Future of Sentinel: An Early-Warning System for Pandemic Preemption and Response

Author

Yolanda Botti-Lodovico, Parvathy Nair, Dolo Nosamiefan, Matthew Stremlau, Stephen Schaffner, Sebastian V. Agignoae, John Oke Aiyepada, Fehintola V. Ajogbasile, George O. Akpede, Foday Alhasan, Kristian G. Andersen, Danny A. Asogun, Oladele Oluwafemi Ayodeji, Aida S. Badiane, Kayla Barnes, Matthew R. Bauer, Antoinette Bell-Kareem, Muoebonam Ekene Benard, Ebo Ohomoime Benevolence, Osiemi Blessing, Chloe K. Boehm, Matthew L. Boisen, Nell G. Bond, Luis M. Branco, Michael J. Butts, Amber Carter, Andres Colubri, Awa B. Deme, Katherine C. DeRuff, Younousse Diédhiou, Akhilomen Patience Edamhande, Siham Elhamoumi, Emily J. Engel, Philomena Eromon, Mosoka Fallah, Onikepe A. Folarin, Ben Fry, Robert Garry, Amy Gaye, Michael Gbakie, Sahr M. Gevao, Gabrielle Gionet, Adrianne Gladden-Young, Augustine Goba, Jules Francois Gomis, Anise N. Happi, Mary Houghton, Chikwe Ihekwuazu, Christopher Ojemiega Iruolagbe, Jonathan Jackson, Simbirie Jalloh, Jeremy Johnson, Lansana Kanneh, Adeyemi Kayode, Molly Kemball, Ojide Chiedozie Kingsley, Veronica Koroma, Dylan Kotliar, Samar Mehta, Hayden C. Metsky, Airende Michael, Marzieh Ezzaty Mirhashemi, Kayvon Modjarrad, Mambu Momoh, Cameron A. Myhrvold, Okonofua Grace Naregose, Tolla Ndiaye, Mouhamadou Ndiaye, Aliou Ndiaye, Erica Normandin, Ikponmwosa Odia, Judith Uche Oguzie, Sylvanus A. Okogbenin, Peter O. Okokhere, Johnson Okolie, Idowu B. Olawoye, Testimony J. Olumade, Paul E. Oluniyi, Omigie Omoregie, Daniel J. Park, Mariétou Faye Paye, Brittany Petros, Anthony A. Philippakis, Abechi Priscilla, Alan Ricks, Anne Rimoin, John Demby Sandi, John S. Schieffelin, Monica Schreiber, Mame Cheikh Seck, Sameed Siddiqui, Katherine Siddle, Allison R. Smither, Mouhamad Sy, Ngayo Sy, Christopher H. Tomkins-Tinch, Oyewale Tomori, Chinedu Ugwu, Jessica N. Uwanibe, Eghosasere Anthonia Uyigue, Dada Ireti Victoria, Anika Vinzé, Megan E. Vodzak, Nicole Welch, Haja Isatta Wurie, Daba Zoumarou, Donald S. Grant, Daouda Ndiaye, Bronwyn MacInnis, Pardis C. Sabeti, and Christian Happi

Subjects
pandemic preemption, pandemic response, diagnostic tools, bioinformatics, genomic surveillance, infectious disease, Microbiology, QR1-502
Abstract

While investigating a signal of adaptive evolution in humans at the gene LARGE, we encountered an intriguing finding by Dr. Stefan Kunz that the gene plays a critical role in Lassa virus binding and entry. This led us to pursue field work to test our hypothesis that natural selection acting on LARGE—detected in the Yoruba population of Nigeria—conferred resistance to Lassa Fever in some West African populations. As we delved further, we conjectured that the “emerging” nature of recently discovered diseases like Lassa fever is related to a newfound capacity for detection, rather than a novel viral presence, and that humans have in fact been exposed to the viruses that cause such diseases for much longer than previously suspected. Dr. Stefan Kunz’s critical efforts not only laid the groundwork for this discovery, but also inspired and catalyzed a series of events that birthed Sentinel, an ambitious and large-scale pandemic prevention effort in West Africa. Sentinel aims to detect and characterize deadly pathogens before they spread across the globe, through implementation of its three fundamental pillars: Detect, Connect, and Empower. More specifically, Sentinel is designed to detect known and novel infections rapidly, connect and share information in real time to identify emerging threats, and empower the public health community to improve pandemic preparedness and response anywhere in the world. We are proud to dedicate this work to Stefan Kunz, and eagerly invite new collaborators, experts, and others to join us in our efforts.

Published
2021
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