Article
Clinical Neurology
Valentina Zschernack, Stephanie T. Junger, Martin Mynarek, Stefan Rutkowski, Maria Luisa Garre, Martin Ebinger, Marie Neu, Joerg Faber, Bernhard Erdlenbruch, Alexander Claviez, Stefan Bielack, Triantafyllia Brozou, Michael C. Fruehwald, Evelyn Doerner, Verena Dreschmann, Annika Stock, Laszlo Solymosi, Juergen Hench, Stephan Frank, Christian Vokuhl, Andreas Waha, Felipe Andreiuolo, Torsten Pietsch
Summary: Two distinct genetically defined entities of ependymoma in the supratentorial compartment, characterized by a C11orf95-RELA or a YAP-MAMLD1 fusion, have been identified. However, this study shows the existence of at least two more types (RELA-like and tanycytic) of supratentorial ependymomas without these genetic features.
ACTA NEUROPATHOLOGICA
(2021)
Article
Multidisciplinary Sciences
Yanbo Wang, John Mallon, Haobo Wang, Digvijay Singh, Myung Hyun Jo, Boyang Hua, Scott Bailey, Taekjip Ha
Summary: The research discovered that the HNH domain of CRISPR-Cas9 exhibits high flexibility post-DNA cleavage, exposing a 3' flap after cleavage of the non-target strand, potentially interacting with the DNA repair machinery. These findings reveal the regulatory role of DNA cleavage activity on Cas9 conformation and suggest potential applications in biotechnology.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Chemistry, Multidisciplinary
Haohao Yin, Bangguo Zhou, Caihong Dong, Yan Zhang, Jifeng Yu, Yinying Pu, Wei Feng, Liping Sun, Hui Hu, Yu Chen, Huixiong Xu
Summary: This study successfully addressed the issue of reduced efficacy in photothermal ablation due to upregulation of TXNDC5 gene expression following PTT by constructing a NIR-II light-controlled CRISPR/Cas9 nanosystem based on silicene. The system enabled remote reprogramming of the tumor microenvironment, enhancing photonic tumor ablation effect and significantly improving gene editing efficiency. This approach not only offers a solution to the challenges in photothermal tumor therapy, but also demonstrates the wide biomedical application potential of 2D silicene nanosheets.
ADVANCED FUNCTIONAL MATERIALS
(2021)
Article
Biotechnology & Applied Microbiology
Chunwei Zheng, Shun-Qing Liang, Bin Liu, Pengpeng Liu, Suet-Yan Kwan, Scot A. Wolfe, Wen Xue
Summary: Prime editor (PE) has great potential for gene therapy, but it is challenging to deliver PE in vivo. In this study, a compact PE without the RNase H domain was developed, which showed comparable editing efficiency with full-length PE. Using a Cas9 split site, robust editing was achieved in both cells and mouse liver. Furthermore, the compact PE efficiently mediated gene insertion in mouse liver without the stop codon read-through effect observed with full-length PE, indicating its potential for advancing prime editing in vivo.
Article
Chemistry, Multidisciplinary
Weimin Ruan, Mingzhu Jiao, Sen Xu, Muhammad Ismail, Xuan Xie, Yang An, Haixing Guo, Rongjun Qian, Bingyang Shi, Meng Zheng
Summary: The brain-targeted CRISPR/Cas9 based nanomedicine successfully crossed the blood-brain barrier and accumulated in brain tumors with the help of angiopep-2 peptide functionality, leading to an improved gene knockout efficiency for glioblastoma treatment and suppression of tumor growth.
JOURNAL OF CONTROLLED RELEASE
(2022)
Article
Oncology
Taciani de Almeida Magalhaes, Gustavo Alencastro Veiga Cruzeiro, Graziella Ribeiro de Sousa, Bernhard Englinger, Luis Fernando Peinado Nagano, Mathew Ancliffe, Keteryne Rodrigues da Silva, Li Jiang, Johannes Gojo, Yulu Cherry Liu, Brooke Carline, Mani Kuchibhotla, Fabiano Pinto Saggioro, Suely Kazue Nagahashi Marie, Sueli Mieko Oba-Shinjo, Jose Andres Yunes, Rosane Gomes de Paula Queiroz, Carlos Alberto Scrideli, Raelene Endersby, Mariella G. Filbin, Kleiton Silva Borges, Adrian Salic, Luiz Gonzaga Tone, Elvis Terci Valera
Summary: This study reveals the crucial role of the Hedgehog (Hh) pathway in ST-RELA tumor growth and suggests that the rescue of primary cilia represents a vulnerability of ST-RELA EPNs.
Article
Chemistry, Multidisciplinary
Saed Abbasi, Satoshi Uchida, Kazuko Toh, Theofilus A. Tockary, Anjaneyulu Dirisala, Kotaro Hayashi, Shigeto Fukushima, Kazunori Kataoka
Summary: Co-delivery of Cas9 mRNA and sgRNA using PEGylated polyplex micelle (PM) enhances genome editing efficiency in a variety of cell types, including brain parenchymal cells, with improved sgRNA stability and higher editing efficiency than delivery of Cas9 mRNA or sgRNA alone. This approach shows promise for in vivo genome editing and demonstrates the potential of PMs for co-encapsulation of Cas9 mRNA and sgRNA.
JOURNAL OF CONTROLLED RELEASE
(2021)
Article
Neurosciences
Arnault Tauziede-Espariat, Aurore Siegfried, Yvan Nicaise, Thomas Kergrohen, Philipp Sievers, Alexandre Vasiljevic, Alexandre Roux, Edouard Dezamis, Chiara Benevello, Marie-Christine Machet, Sophie Michalak, Chloe Puiseux, Francisco Llamas-Gutierrez, Pierre Leblond, Franck Bourdeaut, Jacques Grill, Christelle Dufour, Lea Guerrini-Rousseau, Samuel Abbou, Volodia Dangouloff-Ros, Nathalie Boddaert, Raphael Saffroy, Lauren Hasty, Ellen Wahler, Melanie Pages, Felipe Andreiuolo, Emmanuele Lechapt, Fabrice Chretien, Thomas Blauwblomme, Kevin Beccaria, Johan Pallud, Stephanie Puget, Emmanuelle Uro-Coste, Pascale Varlet
Summary: The study extensively characterized non-RELA ZFTA-fused supratentorial tumors, revealing significant histopathological heterogeneity and similarities in MRI features to RELA fusion-positive cases. Additionally, distinct clusters of ZFTA fusion-positive tumors were identified, pointing to varying characteristics within different clusters.
ACTA NEUROPATHOLOGICA COMMUNICATIONS
(2021)
Article
Biochemistry & Molecular Biology
Xiaopeng Song, Yaxiong Cui, Yanxiao Wang, Yizhe Zhang, Qi He, Zhenyang Yu, Chengfang Xu, Huimin Ning, Yuying Han, Yunting Cai, Xuan Cheng, Jian Wang, Yan Teng, Xiao Yang, Jun Wang
Summary: In this study, the AAV-BR1-CRISPR system was used to specifically knock out target genes in brain endothelial cells of adult mice, demonstrating its effectiveness in rapidly identifying endothelial genes that regulate blood-brain barrier integrity in vivo.
INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Lin Zhu, Xiaoyan Yang, Juyi Li, Xiong Jia, Xiangli Bai, Ying Zhao, Wenzhuo Cheng, Meng Shu, Yan Zhu, Si Jin
Summary: Gene therapy using CRISPR/Cas9 successfully corrected Leptin gene mutations in ob/ob mice, restoring the production of LEPTIN protein and providing a new therapeutic strategy for human monogenic diseases.
JOURNAL OF GENETICS AND GENOMICS
(2021)
Article
Biology
Han-Xiang Deng, Hong Zhai, Yong Shi, Guoxiang Liu, Jessica Lowry, Bin Liu, Eanna B. Ryan, Jianhua Yan, Yi Yang, Nigel Zhang, Zhihua Yang, Erdong Liu, Yongchao C. Ma, Teepu Siddique
Summary: Deng et al. assess the effects of CRISPR/Cas9-mediated genome editing in two transgenic mouse models of amyotrophic lateral sclerosis (ALS) for up to 2 years. They find that the genomic editing prevented the development of ALS-like pathology without any notable side-effects, which provides preclinical evidence of the effectiveness and long-term safety of the CRISPR/Cas9 therapeutic approach.
COMMUNICATIONS BIOLOGY
(2021)
Article
Neurosciences
Shilpy Jha, Prit Benny Mulgulwar, Mehar Chand Sharma, Suvendu Purkait, Ashis Pattnaik, Mukund Namdev Sable
Summary: Lipogenic differentiation in ependymoma is rare, and there are few reported cases. The grading of this type of ependymoma is based solely on histomorphology and does not include molecular subtyping. This is the first documentation of a fusion negative supratentorial anaplastic ependymoma with lipogenic differentiation.
Review
Biochemistry & Molecular Biology
Si-Wei Wang, Chao Gao, Yi-Min Zheng, Li Yi, Jia-Cheng Lu, Xiao-Yong Huang, Jia-Bin Cai, Peng-Fei Zhang, Yue-Hong Cui, Ai-Wu Ke
Summary: The CRISPR/Cas9 gene editing technology has made significant progress in oncological research, providing a powerful tool for exploring the mechanism of cancer, establishing tumor models, and studying drug targets.
Article
Genetics & Heredity
Menglong Chen, Hui Shi, Shixue Gou, Xiaomin Wang, Lei Li, Qin Jin, Han Wu, Huili Zhang, Yaqin Li, Liang Wang, Huan Li, Jinfu Lin, Wenjing Guo, Zhiwu Jiang, Xiaoyu Yang, Anding Xu, Yuling Zhu, Cheng Zhang, Liangxue Lai, Xiaoping Li
Summary: This study demonstrated the high efficiency of large-scale excision of mutant DMD exons in restoring dystrophin protein expression in a patient-derived stem cell model. CRISPR-mediated genome editing with Cas12a showed similar efficacy to Cas9 in correcting DMD mutations. In a PDX DMD mouse model, over 10% of human DMD muscle fibers expressed dystrophin after treatment with large-scale excision strategies, indicating functional restoration of dystrophin in vivo.
Article
Biochemistry & Molecular Biology
Seak Hee Oh, Hye-Jin Lee, Mi Kyoung Ahn, Mi Yeon Jeon, Jeong-Soo Yoon, Yeon Ju Jung, Gyeong-Nam Kim, In-Jeoung Baek, Inki Kim, Kyung Mo Kim, Young Hoon Sung
Summary: CRISPR-Cas systems, such as Cas9 and Cpf1, are effective tools for generating gene knockout mouse models. A hybrid guide RNA system combining Cas9 and Cpf1 has been developed for multiplex gene editing, showing successful results in targeting multiple genes in mouse embryos.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2021)
Article
Clinical Neurology
James L. Ross, Zhihong Chen, Cameron J. Herting, Yura Grabovska, Frank Szulzewsky, Montserrat Puigdelloses, Lenore Monterroza, Jeffrey Switchenko, Nitin R. Wadhwani, Patrick J. Cimino, Alan Mackay, Chris Jones, Renee D. Read, Tobey J. MacDonald, Matthew Schniederjan, Oren J. Becher, Dolores Hambardzumyan
Summary: This study highlights the importance of TAMs in paediatric HGG, emphasizing the potent inflammatory effects of PDGFB in paediatric HGG and identifying CCL3 as a key chemokine in these processes.
Article
Developmental Biology
Frank Szulzewsky, Eric C. Holland, Valeri Vasioukhin
Summary: YAP1 is a crucial transcriptional co-activator involved in both normal tissue homeostasis and cancer development. Its activity is regulated by various mechanisms such as the Hippo signaling pathway and miRNAs, and different therapeutic strategies targeting YAP1 functions are being explored.
DEVELOPMENTAL BIOLOGY
(2021)
Article
Neurosciences
Nicholas Nuechterlein, Linda G. Shapiro, Eric C. Holland, Patrick J. Cimino
Summary: Knowledge of 1p/19q-codeletion and IDH1/2 mutational status is crucial for the study of diffuse gliomas. This study developed a classification system using SCNA data to predict these molecular markers accurately, achieving near perfect classification results. The system was validated on multiple datasets and successfully applied to additional cohorts for subtype labeling.
ACTA NEUROPATHOLOGICA COMMUNICATIONS
(2021)
Letter
Hematology
Rohan Kodgule, Jie Chen, Pooja Khonde, Joshua Robinson, Amy D'Albora, Lisa Cook, Catrina C. Fronick, Robert Fulton, Sridhar Nonavinkere Srivatsan, Patrick J. Cimino, Eric J. Duncavage
Review
Pathology
Rebecca A. Yoda, Patrick J. Cimino
Summary: Hemangioblastoma is a vascular tumor of the central nervous system associated with loss of function of the VHL gene. It primarily occurs in the cerebellum, brainstem, and spinal cord, leading to significant morbidity and mortality in affected patients. Accurate diagnosis is crucial for surgical neuropathology, as other VHL-associated tumors may mimic its histology.
JOURNAL OF PATHOLOGY AND TRANSLATIONAL MEDICINE
(2022)
Article
Oncology
James H. Park, Abdullah H. Feroze, Samuel N. Emerson, Anca B. Mihalas, C. Dirk Keene, Patrick J. Cimino, Adrian Lopez Garcia de Lomana, Kavya Kannan, Wei-Ju Wu, Serdar Turkarslan, Nitin S. Baliga, Anoop P. Patel
Summary: In this study, the authors modeled the tumor evolutionary trajectories during standard-of-care treatment for glioblastoma using multi-omic single-cell analysis. They identified a network of regulators that mediate treatment-induced shifts in tumor cell states and developed consensus networks that modulate cell state transitions across primary and recurrent tumor cells. By matching targeted therapies to active regulatory networks, they proposed a framework for applying single-cell-based precision medicine approaches to individual patients in different treatment settings.
NPJ PRECISION ONCOLOGY
(2022)
Article
Clinical Neurology
Patrick J. Cimino, Courtney Ketchum, Rust Turakulov, Omkar Singh, Zied Abdullaev, Caterina Giannini, Peter Pytel, Giselle Yvette Lopez, Howard Colman, MacLean P. Nasrallah, Mariarita Santi, Igor Lima Fernandes, Jeff Nirschl, Sonika Dahiya, Stewart Neill, David Solomon, Eilis Perez, David Capper, Haresh Mani, Dario Caccamo, Matthew Ball, Michael Badruddoja, Rati Chkheidze, Sandra Camelo-Piragua, Joseph Fullmer, Sanda Alexandrescu, Gabrielle Yeaney, Charles Eberhart, Maria Martinez-Lage, Jie Chen, Leor Zach, B. K. Kleinschmidt-DeMasters, Marco Hefti, Maria-Beatriz Lopes, Nicholas Nuechterlein, Craig Horbinski, Fausto J. Rodriguez, Martha Quezado, Drew Pratt, Kenneth Aldape
Summary: This study provides further evaluation and classification of high-grade astrocytoma with piloid features (HGAP). The study identifies three distinct subtypes of HGAP and discovers characteristic genetic mutations and epigenetic changes. This research is important for understanding the pathogenesis and clinical characteristics of HGAP.
ACTA NEUROPATHOLOGICA
(2023)
Article
Clinical Neurology
Zhichao Wu, Sharika Rajan, Hye-Jung Chung, Mark Raffeld, Pavalan Panneer Selvam, Leonille Schweizer, Arie Perry, David Samuel, Caterina Giannini, Aditya Ragunathan, Matthew P. Frosch, Michael S. Marshall, Daniel R. Boue, Kliment Donev, Stewart G. Neill, Igor Fernandes, Adam Resnick, Brian Rood, Thomas J. Cummings, Anne F. Buckley, Linda Szymanski, Osorio Lopes Abath Neto, Leor Zach, Howard Colman, Samuel Cheshier, Jennifer Ziskin, Manoj Tyagi, David Capper, Zied Abdullaev, Patrick J. Cimino, Martha Quezado, Drew Pratt, Kenneth Aldape
ACTA NEUROPATHOLOGICA
(2022)
Article
Multidisciplinary Sciences
Siobhan S. Pattwell, Sonali Arora, Nicholas Nuechterlein, Michael Zager, Keith R. Loeb, Patrick J. Cimino, Nikolas C. Holland, Noemi Reche-Ley, Hamid Bolouri, Damian A. Almiron Bonnin, Frank Szulzewsky, Vaishnavi V. Phadnis, Tatsuya Ozawa, Michael J. Wagner, Michael C. Haffner, Junyue Cao, Jay Shendure, Eric C. Holland
Summary: This article highlights the previously unidentified role of the neurotrophin receptor splice variant TrkB.T1 in neurodevelopment, embryogenesis, transformation, and oncogenesis. TrkB.T1 is an important isoform in these processes and is expressed in both embryonic and adult tumors. The study also reveals its interaction with developmental and oncogenic signaling pathways, suggesting its potential to reshape our understanding of developmental systems and oncology.
Article
Oncology
Yang Liu, Fu-Ju Chou, Fengchao Lang, Meili Zhang, Hua Song, Wei Zhang, Dionne L. Davis, Nicole J. Briceno, Yang Zhang, Patrick J. Cimino, Kareem A. Zaghloul, Mark R. Gilbert, Terri S. Armstrong, Chunzhang Yang
Summary: This study reveals that mutations of the IDH gene are common in human malignancies and play critical roles in malignant transformation. The PI3K/AKT signaling pathway is enhanced in IDH-mutated cancer cells. Combining the AKT inhibitor Ipa with the genotoxic agent TMZ shows synergistic therapeutic effect in IDH-mutated cancer cells.
CLINICAL CANCER RESEARCH
(2023)
Letter
Clinical Neurology
Allison Shelbourn, Nicholas Nuechterlein, Carolina Angelica Parada, Jessica Eaton, Mallory Tucker, Manuel Ferreira Jr, Patrick J. Cimino
JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY
(2023)
Letter
Clinical Neurology
Nicholas Nuechterlein, Allison Shelbourn, Patrick J. Cimino
JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY
(2023)
Article
Cell Biology
Frank Szulzewsky, Sonali Arora, Aleena K. S. Arakaki, Philipp Sievers, Damian A. Almiron Bonnin, Patrick J. Paddison, Felix Sahm, Patrick J. Cimino, Taranjit S. Gujral, Eric C. Holland
Summary: The study investigates the role of YAP1-MAML2 gene fusion in the formation of meningioma and demonstrates that YAP1-MAML2 is a causal oncogenic driver in meningioma.
GENES & DEVELOPMENT
(2022)
Article
Oncology
Jinxiang Dai, Patrick J. Cimino, Kenneth H. I. I. I. I. I. I. Gouin, Candice A. Grzelak, Alexander Barrett, Andrea R. Lim, Annalyssa Long, Stephanie Weaver, Lindsey T. Saldin, Aiyedun Uzamere, Vera Schulte, Nigel Clegg, Laura Pisarsky, David Lyden, Mina J. Bissell, Simon Knott, Alana L. Welm, Jason H. Bielas, Kirk C. Hansen, Frank Winkler, Eric C. Holland, Cyrus M. Ghajar
Summary: This study reveals that escape from the single-cell or micrometastatic state is the rate-limiting step towards brain metastasis, with laminin-211 deposited by astrocytes playing a key role in inducing DTC dormancy.