Article
Multidisciplinary Sciences
Danielle E. Anderson, Jin Cui, Qian Ye, Baoying Huang, Ya Tan, Chao Jiang, Wenhong Zu, Jing Gong, Weiqiang Liu, So Young Kim, Biao Guo Yan, Kristmundur Sigmundsson, Xiao Fang Lim, Fei Ye, Peihua Niu, Aaron T. Irving, Haoyu Zhang, Yefeng Tang, Xuming Zhou, Yu Wang, Wenjie Tan, Lin-Fa Wang, Xu Tan
Summary: Bats are found to play a crucial role in the zoonotic transmission of major viral diseases, and they exhibit unique innate immune characteristics that are essential for viral replication. The gene MTHFD1 is identified as a key player in the viral tolerance of both bat and human cells, presenting a potential target for developing broad-spectrum antiviral therapy. Research on bats provides valuable insights into understanding genetic factors influencing viral interactions and responses.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Multidisciplinary Sciences
Raghuvaran Shanmugam, Mert Burak Ozturk, Joo-Leng Low, Semih Can Akincilar, Joelle Yi Heng Chua, Matan Thangavelu Thangavelu, Giridharan Periyasamy, Ramanuj DasGupta, Vinay Tergaonkar
Summary: Understanding the regulatory mechanisms of mutant hTERT promoters can lead to the identification of potential therapeutic targets for specifically blocking telomerase reactivation in cancer cells.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Multidisciplinary Sciences
David Estoppey, Gabi Schutzius, Christian Kolter, Adrian Salathe, Tiffany Wunderlin, Amandine Meyer, Florian Nigsch, Tewis Bouwmeester, Dominic Hoepfner, Susan Kirkland
Summary: BET bromodomain inhibitors show promise as therapeutic agents in cancer treatment, but face challenges in clinical progression, requiring increased understanding of their mechanisms of action and identification of biomarkers.
Review
Biotechnology & Applied Microbiology
George Alyateem, Heidi M. Wade, Aaron A. Bickert, Crystal C. Lipsey, Priya Mondal, MacKinzie D. Smith, Rania M. Labib, Beverly A. Mock, Robert W. Robey, Michael M. Gottesman
Summary: Despite the development of targeted anti-cancer drugs, the curative treatment of metastatic solid tumors remains challenging due to drug resistance. The use of CRISPR technology to generate cancer cell libraries carrying sgRNAs has shown promise in identifying novel mechanisms of drug resistance. Strategies using CRISPR knockout, activation, and inhibition screens, as well as specialized approaches to identify multiple contributing genes, offer a potential way to accelerate understanding of drug resistance in cancer.
CANCER GENE THERAPY
(2023)
Article
Biology
Govind Pai, Khashayar Roohollahi, Davy Rockx, Yvonne de Jong, Chantal Stoepker, Charlotte Pennings, Martin Rooimans, Lianne Vriend, Sander Piersma, Connie R. Jimenez, Renee X. De Menezes, Victor W. Van Beusechem, Ruud H. Brakenhoff, Hein Te Riele, Rob M. F. Wolthuis, Josephine C. Dorsman
Summary: Fanconi anemia (FA) is a rare chromosomal-instability syndrome caused by mutations in FA DNA-repair genes. This study identified RBBP9 as a potential therapeutic target for FA-HNSCC through genome-wide siRNA screens. Low dose of the FDA-approved drug Emetine targeting RBBP9 can kill FA-HNSCC cells without harming non-tumor FA cells. This research provides insights into addressing treatment challenges in FA-HNSCC.
COMMUNICATIONS BIOLOGY
(2023)
Article
Oncology
Xiaojing Lu, Yuzhi Pang, Hui Cao, Xiaoxiao Liu, Lin Tu, Yanying Shen, Xiaona Jia, Jen-Chieh Lee, Yuexiang Wang
Summary: CDK1 is highly expressed in advanced GIST and essential for GIST proliferation. Inhibition of CDK1 with RO-3306 showed promising results in reducing tumor growth in both imatinib-resistant and imatinib-sensitive GIST xenograft mouse models, suggesting CDK1 as a potential therapeutic target for advanced GIST patients.
Article
Multidisciplinary Sciences
Alexendar R. Perez, Laura Sala, Richard K. Perez, Joana A. Vidigal
Summary: Off-target effects are common in CRISPR screens, but the computational tool CSC corrects for these effects in gRNA depletion assays, improving overall sensitivity and specificity without discarding unspecific guides.
NATURE COMMUNICATIONS
(2021)
Article
Biotechnology & Applied Microbiology
Yuechao Wu, Qiurong Ren, Zhaohui Zhong, Guanqing Liu, Yangshuo Han, Yu Bao, Li Liu, Shuyue Xiang, Shuo Liu, Xu Tang, Jianping Zhou, Xuelian Zheng, Simon Sretenovic, Tao Zhang, Yiping Qi, Yong Zhang
Summary: PAM-relaxed Cas9 nucleases, cytosine base editors, and adenine base editors are promising tools for precise genome editing in plants. However, their genome-wide off-target effects and background mutations are not well understood. In this study, the whole-genome sequencing analyses of transgenic rice plants edited by different editing tools were conducted, revealing distinct gRNA-dependent off-target sites preferred by Cas9 nucleases and base editors. Additionally, the ABE8e base editor showed a high number of A-to-G off-target mutations at TA motif sites. The study also investigated the timeline and mechanism of somaclonal variation caused by tissue culture, which contributes to background mutations.
PLANT BIOTECHNOLOGY JOURNAL
(2022)
Article
Cell Biology
Jicheng Yang, Fusheng Guo, Hui San Chin, Gao Bin Chen, Chow Hiang Ang, Qingsong Lin, Wanjin Hong, Nai Yang Fu
Summary: Through genome-wide loss-of-function CRISPR-Cas9 screens, this study identified multiple genes involved in endoplasmic reticulum targeting, different biological processes in the Golgi apparatus, and protein trafficking, which are potential regulators of tetraspanin trafficking. Additionally, the study found that biantennary N-glycans generated by MGAT1/2 are crucial for cell-surface tetraspanin expression. Furthermore, SPPL3 was discovered to control cell-surface tetraspanin expression through mechanisms associated with lacto-series glycolipid biosynthesis. These findings provide critical insights into the molecular regulation of tetraspanin presentation on the cell surface and have implications for manipulating their functions, including cancer cell invasion.
Article
Genetics & Heredity
Scott B. Biering, Sylvia A. Sarnik, Eleanor Wang, James R. Zengel, Sarah R. Leist, Alexandra Schafer, Varun Sathyan, Padraig Hawkins, Kenichi Okuda, Cyrus Tau, Aditya R. Jangid, Connor Duffy, Jin Wei, Rodney C. Gilmore, Mia Madel Alfajaro, Madison S. Strine, Xammy Nguyenla, Erik Van Dis, Carmelle Catamura, Livia H. Yamashiro, Julia A. Belk, Adam Begeman, Jessica C. Stark, D. Judy Shon, Douglas M. Fox, Shahrzad Ezzatpour, Emily Huang, Nico Olegario, Arjun Rustagi, Allison S. Volmer, Alessandra Livraghi-Butrico, Eddie Wehri, Richard R. Behringer, Dong-Joo Cheon, Julia Schaletzky, Hector C. Aguilar, Andreas S. Puschnik, Brian Button, Benjamin A. Pinsky, Catherine A. Blish, Ralph S. Baric, Wanda K. O'Neal, Carolyn R. Bertozzi, Craig B. Wilen, Richard C. Boucher, Jan E. Carette, Sarah A. Stanley, Eva Harris, Silvana Konermann, Patrick D. Hsu
Summary: This study identified mucins as key host factors restricting viral infection, through genome-wide CRISPR knockout and activation screens in human lung epithelial cells expressing the SARS-CoV-2 entry factors ACE2 and TMPRSS2. These mucins serve as a significant viral restriction network inhibiting SARS-CoV-2 infection and other respiratory viruses. The findings provide a starting point for new host-directed therapeutics and highlight airway mucins as an important host defense mechanism.
Article
Biochemistry & Molecular Biology
Shiyan Liu, Chong Han, Jingjun Huang, Meihui Li, Jiayu Yang, Guifeng Li, Haoran Lin, Shuisheng Li, Yong Zhang
Summary: In this study, we identified and analyzed the expression pattern of TGF-beta signaling pathway members in mandarin fish during gonadal development. Our results reveal differential expression and participation of TGF-beta signaling pathway members in different stages and sexes of gonadal development.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2023)
Article
Biochemistry & Molecular Biology
Mengfan Tang, Guangsheng Pei, Dan Su, Chao Wang, Xu Feng, Mrinal Srivastava, Zhen Chen, Zhongming Zhao, Junjie Chen
Summary: The study identified that CCNC is a critical survival target in cells with BRCA2 loss, potentially contributing to PARPi resistance.
NUCLEIC ACIDS RESEARCH
(2021)
Article
Cell Biology
Lijie Wang, Wei Xue, Hongxia Zhang, Runze Gao, Houyuan Qiu, Jia Wei, Lina Zhou, Yun-Ni Lei, Xiaocheng Wu, Xiao Li, Chengfang Liu, Jing Wu, Qiubing Chen, Hanhui Ma, Xingxu Huang, Cheguo Cai, Ying Zhang, Bei Yang, Hao Yin, Li Yang, Jia Chen
Summary: The study introduces a novel base editor system, tBE, which efficiently performs C-to-T editing by fusing a cleavable dCDI domain, reducing off-target mutations. The tBE system remains inactive at off-target sites, preventing unintended mutations, and activates for precise base editing at on-target sites.
NATURE CELL BIOLOGY
(2021)
Article
Cell Biology
Guokai Yan, Jinxin Yang, Wen Li, Ao Guo, Jialiang Guan, Ying Liu
Summary: mTORC1 is an essential hub that controls cell growth by integrating nutrient signals. ILF3 is a negative regulator of mTORC1 activity in response to amino acid sensing, and it functions by tethering the GATOR complexes to lysosomes.
NATURE CELL BIOLOGY
(2023)
Review
Virology
Aditi Kanojia, Mansi Sharma, Rishad Shiraz, Shashank Tripathi
Summary: Genome-wide CRISPR screens are an effective tool for identifying and characterizing viral host dependency factors systematically, contributing to our understanding of Flavivirus-Host interactions.
Article
Multidisciplinary Sciences
Eugen Buehler, Yu-Chi Chen, Scott Martin
Article
Multidisciplinary Sciences
Gilad Sivan, Scott E. Martin, Timothy G. Myers, Eugen Buehler, Krysia H. Szymczyk, Pinar Ormanoglu, Bernard Moss
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2013)
Article
Biochemical Research Methods
Shane Marine, Amit Bahl, Marc Ferrer, Eugen Buehler
JOURNAL OF BIOMOLECULAR SCREENING
(2012)
Article
Biochemical Research Methods
EC Buehler, JR Sachs, K Shao, A Bagchi, LH Ungar
Article
Multidisciplinary Sciences
A Theologis, JR Ecker, CJ Palm, NA Federspiel, S Kaul, O White, J Alonso, H Altafi, R Araujo, CL Bowman, SY Brooks, E Buehler, A Chan, QM Chao, HM Chen, RF Cheuk, CW Chin, MK Chung, L Conn, AB Conway, AR Conway, TH Creasy, K Dewar, P Dunn, P Etgu, TV Feldblyum, JD Feng, B Fong, CY Fujii, JE Gill, AD Goldsmith, B Haas, NF Hansen, B Hughes, L Huizar, JL Hunter, J Jenkins, C Johnson-Hopson, S Khan, E Khaykin, CJ Kim, HL Koo, I Kremenetskaia, DB Kurtz, A Kwan, B Lam, S Langin-Hooper, A Lee, JM Lee, CA Lenz, JH Li, YP Li, XY Lin, SX Liu, ZA Liu, JS Luros, R Maiti, A Marziali, J Militscher, M Miranda, M Nguyen, WC Nierman, BI Osborne, G Pai, J Peterson, PK Pham, M Rizzo, T Rooney, D Rowley, H Sakano, SL Salzberg, JR Schwartz, P Shinn, AM Southwick, H Sun, LJ Tallon, G Tambunga, MJ Toriumi, CD Town, T Utterback, S Van Aken, M Vaysberg, VS Vysotskaia, M Walker, DY Wu, GX Yu, CM Fraser, JC Venter, RW Davis