Article
Cell Biology
Jinghui Liu, Yue Zhao, Daheng He, Katelyn M. Jones, Shan Tang, Derek B. Allison, Yanquan Zhang, Jing Chen, Qiongsi Zhang, Xinyi Wang, Chaohao Li, Chi Wang, Lang Li, Xiaoqi Liu
Summary: Enzalutamide (ENZA), a second-generation androgen receptor antagonist, enhances the efficacy of treatment for metastatic prostate cancer (PCa), but resistance remains a challenge. Through a CRISPR-Cas9 knockout screen, casein kinase 1a (CK1a) has been identified as a therapeutic target to overcome ENZA resistance. Inhibition of CK1a stabilizes ATM and restores DNA-damage response signaling, leading to increased cell death and growth arrest.
CELL REPORTS MEDICINE
(2023)
Article
Hematology
Kensuke Sasaki, Takuji Yamauchi, Yuichiro Semba, Jumpei Nogami, Hiroshi Imanaga, Tatsuya Terasaki, Fumihiko Nakao, Koshi Akahane, Takeshi Inukai, Els Verhoeyen, Koichi Akashi, Takahiro Maeda
Summary: This study identified molecules/pathways relevant for IgH-CRLF2-r ALL pathogenesis and found that CRKL and RAS signaling are critical for cell fitness and ruxolitinib sensitivity. The pan-tyrosine kinase inhibitor gilteritinib effectively killed RAS wild-type IgH-CRLF2-r ALL cells, either alone or combined with ruxolitinib. Combining gilteritinib with the MEK1/2 inhibitor trametinib is an effective means to target IgH-CRLF2-r ALL cells regardless of RAS mutational status.
Article
Biochemistry & Molecular Biology
Jangsoon Lee, Huey Liu, Troy Pearson, Toshiaki Iwase, Jon Fuson, Alshad S. Lalani, Lisa D. Eli, Irmina Diala, Debu Tripathy, Bora Lim, Naoto T. Ueno
Summary: This study identified everolimus and trametinib as potential inhibitors that enhance the anti-tumor activity of neratinib in HER2+ breast cancer and TNBC. The combination therapies significantly inhibited tumor growth in xenograft models and activated apoptosis pathway by reducing Ki67 expression.
Article
Biochemistry & Molecular Biology
Annika Kratzel, Jenna N. Kelly, Philip V'kovski, Jasmine Portmann, Yannick Brueggemann, Daniel Todt, Nadine Ebert, Neeta Shrestha, Philippe Plattet, Claudia A. Staab-Weijnitz, Albrecht von Brunn, Eike Steinmann, Ronald Dijkman, Gert Zimmer, Stephanie Pfaender, Volker Thiel
Summary: Over the past 20 years, three highly pathogenic human coronaviruses have emerged, highlighting the serious threat that coronaviruses pose to human health. Research has identified several autophagy-related genes as common host factors required for the replication of coronaviruses, suggesting potential targets for therapeutic intervention using clinically approved drugs.
Article
Medicine, Research & Experimental
Kelly Waldeck, Jessica Van Zuylekom, Carleen Cullinane, Twishi Gulati, Kaylene J. Simpson, Richard W. Tothill, Benjamin Blyth, Rodney J. Hicks
Summary: A genome-wide CRISPR/Cas9 screen identified potential gene targets for sensitivity and resistance to LuTate, offering opportunities for novel combination therapies for NET patients. Regulation of DNA damage repair pathways may enhance the efficacy of LuTate treatment.
Article
Oncology
Mohammad Sultan, Jacob T. Nearing, Justin M. Brown, Thomas T. Huynh, Brianne M. Cruickshank, Emily Lamoureaux, Dejan Vidovic, Margaret L. Dahn, Wasundara Fernando, Krysta M. Coyle, Carman A. Giacomantonio, Morgan G. Langille, Paola Marcato
Summary: The study identified BCL6 as a potential targetable resistance biomarker of paclitaxel response in breast cancer, with knockdown of BCL6 resulting in increased tumor regression and enhanced paclitaxel treatment efficacy. This suggests that targeting BCL6 may be a promising strategy to improve the response to paclitaxel in breast cancer patients.
MOLECULAR ONCOLOGY
(2021)
Article
Cell Biology
Jiequn Li, Chunli Chen, Chenchen Li, Zhiping Hu, Jieqiong Tan, Liuwang Zeng
Summary: This study investigates the molecular mechanisms of ammonia neurotoxicity and potential therapeutic targets for hepatic encephalopathy (HE) through a CRISPR/Cas9 knockout screen. EGLN3 appears to be the most related to ammonia resistance, and its knockdown protects against ammonia-induced apoptosis. The findings suggest that targeting EGLN3 could be a future therapeutic strategy for managing HE.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Biology
Olga T. Schubert, Joshua S. Bloom, Meru J. Sadhu, Leonid Kruglyak, Kevin J. Verstrepen
Summary: This article describes a genetic screening method for studying the encoding of protein abundance regulation in the genome. The researchers identified numerous regulatory relationships and revealed the different roles of specific regulators and broad regulators in protein translation.
Article
Multidisciplinary Sciences
Jianting Shi, Xun Wu, Ziyi Wang, Fang Li, Yujiao Meng, Rebecca M. Moore, Jian Cui, Chenyi Xue, Katherine R. Croce, Arif Yurdagul, John G. Doench, Wei Li, Konstantinos S. Zarbalis, Ira Tabas, Ai Yamamoto, Hanrui Zhang
Summary: This study identified WDFY3 as a novel regulator of efferocytosis through a genome-wide CRISPR screen, revealing its role in promoting LC3 lipidation and lysosomal acidification for the degradation of apoptotic cell components.
NATURE COMMUNICATIONS
(2022)
Article
Multidisciplinary Sciences
Jongoh Shin, Jiyun Bae, Hyeonsik Lee, Seulgi Kang, Sangrak Jin, Yoseb Song, Suhyung Cho, Byung-Kwan Cho
Summary: Acetogenic bacteria have potential in sustainable bioconversion of carbon oxides into biochemicals. Through genome-scale CRISPR interference screening, we identified the fitness contributions of 96% of the genes in E. limosum, revealing the essentiality of certain pathways for autotrophic acetogenesis. We also discovered repression target genes that improved autotrophic growth rates and acetoin production.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Microbiology
Xuezhang Tian, Yaru Zhou, Shaowei Wang, Ming Gao, Yanlin Xia, Yangyang Li, Yunhong Zhong, Wenhao Xu, Lei Bai, Bishi Fu, Yu Zhou, Hye-Ra Lee, Hongyu Deng, Ke Lan, Pinghui Feng, Junjie Zhang
Summary: In this study, SMCHD1 was identified as a cell-intrinsic restriction factor that controls the replication of KSHV and a wide range of herpesviruses by targeting the origins of viral DNA replication. SMCHD1 deficiency facilitated the replication of a murine herpesvirus in vivo. This study helps us to better understand intrinsic antiviral immunity and could contribute to the development of new therapies for herpesvirus infection and related diseases.
Article
Biology
Carlos G. Sanchez, Christopher M. Acker, Audrey Gray, Malini Varadarajan, Cheng Song, Nadire R. Cochran, Steven Paula, Alicia Lindeman, Shaojian An, Gregory McAllister, John Alford, John Reece-Hoyes, Carsten Russ, Lucas Craig, Ketthsy Capre, Christian Doherty, Gregory R. Hoffman, Sarah J. Luchansky, Manuela Polydoro, Ricardo Dolmetsch, Fiona Elwood
Summary: Aggregates of hyperphosphorylated tau protein are pathological markers for various neurodegenerative diseases. A genome-wide CRISPR screen identified regulators of endogenous tau protein, including chromatin modifiers, ubiquitination, and the mTOR pathway. These findings could have implications for future therapeutic strategies in neurodegenerative diseases.
COMMUNICATIONS BIOLOGY
(2021)
Article
Multidisciplinary Sciences
Yunkai Zhu, Fei Feng, Gaowei Hu, Yuyan Wang, Yin Yu, Yuanfei Zhu, Wei Xu, Xia Cai, Zhiping Sun, Wendong Han, Rong Ye, Di Qu, Qiang Ding, Xinxin Huang, Hongjun Chen, Wei Xu, Youhua Xie, Qiliang Cai, Zhenghong Yuan, Rong Zhang
Summary: The SARS-CoV-2 spike protein contains a multi-basic cleavage site that affects virus entry and transmission, as shown in hamster models. Host factors affecting virus entry were identified through a genome-wide CRISPR screen.
NATURE COMMUNICATIONS
(2021)
Article
Multidisciplinary Sciences
Chenyin Wang, Chun Vin Lau, Fuqiang Ma, Chaogu Zheng
Summary: This study reveals the critical role of gut microbiota in regulating neurodegenerative diseases, particularly through influencing the formation and aggregation of amyloid fibrils. This provides a new research direction for the treatment of neurodegenerative diseases.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Genetics & Heredity
Ana Lopez-Varea, Cristina M. Ostale, Patricia Vega-Cuesta, Ana Ruiz-Gomez, Maria F. Organista, Mercedes Martin, Covadonga F. Hevia, Cristina Molnar, Jesus de Celis, Joaquim Culi, Nuria Esteban, Jose F. de Celis
Summary: A study was conducted on a group of UAS-RNAi lines targeting Drosophila genes, identifying a significant number of genes that affect wing formation in fruit flies, resulting in changes in wing size, vein differentiation, wing margin defects, and dorsal-ventral wing surface apposition. Categorizing genes into functional groups helped in determining enriched mutant phenotypes within each group. Integrating expression, phenotypic, and molecular information provided precision in identifying genes affecting wing formation and regulated biological processes.
G3-GENES GENOMES GENETICS
(2021)
Article
Hematology
Gail J. Roboz, Courtney D. DiNardo, Eytan M. Stein, Stephane de Botton, Alice S. Mims, Gabrielle T. Prince, Jessica K. Altman, Martha L. Arellano, Will Donnellan, Harry P. Erba, Gabriel N. Mannis, Daniel A. Pollyea, Anthony S. Stein, Geoffrey L. Uy, Justin M. Watts, Amir T. Fathi, Hagop M. Kantarjian, Martin S. Tallman, Sung Choe, David Dai, Bin Fan, Hongfang Wang, Vickie Zhang, Katharine E. Yen, Stephanie M. Kapsalis, Denice Hickman, Hua Liu, Samuel Agresta, Bin Wu, Eyal C. Attar, Richard M. Stone
Article
Multidisciplinary Sciences
Attila A. Seyhan, Bernard Gregory, Adam P. Cribbs, Sundeept Bhalara, Yizheng Li, Christine Loreth, Ying Zhang, Yongjing Guo, Lih-Ling Lin, Marc Feldmann, Lynn M. Williams, Fionula M. Brennan, Peter C. Taylor
SCIENTIFIC REPORTS
(2020)
Article
Hematology
Eytan M. Stein, Courtney D. DiNardo, Amir T. Fathi, Alice S. Mims, Keith W. Pratz, Michael R. Savona, Anthony S. Stein, Richard M. Stone, Eric S. Winer, Christopher S. Seet, Hartmut Doehner, Daniel A. Pollyea, James K. McCloskey, Olatoyosi Odenike, Bob Loewenberg, Gert J. Ossenkoppele, Prapti A. Patel, Mikhail Roshal, Mark G. Frattini, Frederik Lersch, Aleksandra Franovic, Salah Nabhan, Bin Fan, Sung Choe, Hongfang Wang, Bin Wu, Lei Hua, Caroline Almon, Michael Cooper, Hagop M. Kantarjian, Martin S. Tallman
Summary: Ivosidenib and enasidenib, as targeted oral inhibitors, demonstrated good safety and efficacy when combined with intensive chemotherapy in newly diagnosed mIDH1/2 AML patients, achieving end-of-induction complete remission rates of 55% and 47% respectively.
Article
Oncology
Gabrielle McDonald, Victor Chubukov, John Coco, Kevin Truskowski, Rohini Narayanaswamy, Sung Choe, Mya Steadman, Erin Artin, Anil K. Padyana, Lei Jin, Sebastien Ronseaux, Charles Locuson, Zi-Peng Fan, Tabea Erdmann, Alan Mann, Sebastian Hayes, Mark Fletcher, Kavitha Nellore, Siva Sanjeeva Rao, Hosahalli Subramanya, K. Satish Reddy, Sunil K. Panigrahi, Thomas Antony, Sreevalsam Gopinath, Zhihua Sui, Nelamangala Nagaraja, Lenny Dang, Georg Lenz, Jonathan Hurov, Scott A. Biller, Josh Murtie, Kevin M. Marks, Danielle B. Ulanet
MOLECULAR CANCER THERAPEUTICS
(2020)
Article
Oncology
Courtney D. DiNardo, Anthony S. Stein, Eytan M. Stein, Amir T. Fathi, Olga Frankfurt, Andre C. Schuh, Hartmut Dohner, Giovanni Martinelli, Prapti A. Patel, Emmanuel Raffoux, Peter Tan, Amer M. Zeidan, Stephane de Botton, Hagop M. Kantarjian, Richard M. Stone, Mark G. Frattini, Frederik Lersch, Jing Gong, Diego A. Gianolio, Vickie Zhang, Aleksandra Franovic, Bin Fan, Meredith Goldwasser, Scott Daigle, Sung Choe, Bin Wu, Thomas Winkler, Paresh Vyas
Summary: The combination therapy of ivosidenib and azacitidine showed promising results in treating IDH1-mutant acute myeloid leukemia, with a well-tolerated safety profile and deep, durable responses observed in patients, especially those achieving complete remission and mIDH1 mutation clearance in bone marrow cells.
JOURNAL OF CLINICAL ONCOLOGY
(2021)
Article
Oncology
Elia Aguado-Fraile, Ania Tassinari, Yuko Ishii, Carlie Sigel, Maeve A. Lowery, Lipika Goyal, Camelia Gliser, Liewen Jiang, Shuchi S. Pandya, Bin Wu, Nabeel Bardeesy, Sung Choe, Vikram Deshpande
Summary: The study reveals that ivosidenib can induce hepatocyte differentiation and inhibit biliary fate, cell cycle progression, and AKT pathway activity in mIDH1 IHCC patients with prolonged PFS, suggesting a differentiation-based therapeutic approach for solid tumors.
Article
Oncology
Courtney D. DiNardo, Eytan M. Stein, Arnaud Pigneux, Jessica K. Altman, Robert Collins, Harry P. Erba, Justin M. Watts, Geoffrey L. Uy, Thomas Winkler, Hongfang Wang, Sung Choe, Hua Liu, Bin Wu, Stephanie M. Kapsalis, Gail J. Roboz, Stephane de Botton
Letter
Hematology
Emily F. Mason, Olga Pozdnyakova, Mikhail Roshal, Amir T. Fathi, Eytan M. Stein, P. Brent Ferrell, Aaron C. Shaver, Mark Frattini, Hongfang Wang, Lei Hua, Jimmy Mu, Sung Choe, Rengyi Xu, Caroline Almon, Michael Cooper, Richard M. Stone, Robert P. Hasserjian, Michael R. Savona
Article
Oncology
Ingo K. Mellinghoff, Marta Penas-Prado, Katherine B. Peters, Howard A. Burris, Elizabeth A. Maher, Filip Janku, Gregory M. Cote, Macarena de la Fuente, Jennifer L. Clarke, Benjamin M. Ellingson, Saewon Chun, Robert J. Young, Hua Liu, Sung Choe, Min Lu, Kha Le, Islam Hassan, Lori Steelman, Shuchi S. Pandya, Timothy F. Cloughesy, Patrick Y. Wen
Summary: Vorasidenib demonstrated favorable safety profile and preliminary antitumor activity in patients with non-enhancing mIDH LGG, with a median progression-free survival of 36.8 months.
CLINICAL CANCER RESEARCH
(2021)
Article
Oncology
Yiqun Zhang, Lanlan Zhou, Howard Safran, Robyn Borsuk, Rishi Lulla, Nikos Tapinos, Attila A. Seyhan, Wafik S. El-Deiry
Summary: Combining EZH2 inhibitors or HDACi with ONC201 can enhance the effectiveness of treatment on multiple cancer cell lines, possibly through reducing H3K27 methylation. Additionally, synergistic effects were observed in multiple cancer cell lines treated with EPZ-6438 or vorinostat in combination with ONC201, which can promote apoptosis in the cells.
Review
Biochemistry & Molecular Biology
Ilyas Sahin, Andrew George, Attila A. Seyhan
Summary: Comprehensive genomic studies have uncovered various dysregulated RNA processing mechanisms in cancer, such as abnormal mRNA and pre-mRNA processing and pathogenically spliced events, leading to altered protein expression levels and potential therapeutic vulnerabilities. The discovery of these alterations not only offers insights into cancer pathogenesis but also presents novel opportunities for targeted therapies.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Biochemistry & Molecular Biology
Shengliang Zhang, Lindsey Carlsen, Liz Hernandez Borrero, Attila A. Seyhan, Xiaobing Tian, Wafik S. El-Deiry
Summary: This article summarizes the current progress in targeting wild-type and mutant p53 for cancer therapy using biotherapeutic and biopharmaceutical methods. Strategies include boosting p53 activity, restoring p53 pathway function, targeting p53 in immunotherapy, and combination therapies.
Review
Biochemistry & Molecular Biology
Attila A. Seyhan, Claudio Carini
Summary: Despite the success of immune checkpoint inhibitors (ICI) in cancer treatment, many patients, including those with melanoma, do not benefit long-term from these therapies. There is a need for predictive biomarkers to identify patients who will respond to targeted treatments. Genomic correlations with response and resistance to ICI are being studied to enhance patient outcomes. Emerging genomic signatures, such as neoantigens, antigen presentation, DNA repair, and oncogenic pathways, may play a role in ICI response. Understanding the genomic factors influencing response to ICI will aid in the development of novel biomarkers and strategies to overcome resistance.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Biochemistry & Molecular Biology
Attila A. Seyhan
Summary: There is an urgent need for robust and reliable biomarkers for early diagnosis, prognosis, and prediction of response to specific treatments in aggressive and deadly cancers, such as pancreatic cancer. Liquid biopsy-based miRNA profiling shows potential for fulfilling this need. MiRNAs are non-coding RNAs that regulate gene expression and have emerged as potential diagnostic, prognostic, predictive, and therapeutic biomarkers.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Biochemistry & Molecular Biology
Alexander G. Raufi, Michael S. May, Matthew J. Hadfield, Attila A. Seyhan, Wafik S. El-Deiry
Summary: Pancreatic cancer is a highly aggressive malignancy with late detection and high recurrence rate. Liquid biopsies represent an emerging group of technologies that can help with diagnosis, prognosis, treatment response prediction, and recurrence detection. Although not yet approved for routine use, the increasing sensitivity and specificity of contemporary liquid biopsy platforms will likely change clinical practice in the near future.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)