Article
Multidisciplinary Sciences
Kendall J. Condon, Jose M. Orozco, Charles H. Adelmann, Jessica B. Spinelli, Pim W. van der Helm, Justin M. Roberts, Tenzin Kunchok, David M. Sabatini
Summary: Our study identified a catalog of genes that impact the mTORC1 pathway and clarified the multifaceted ways in which mTORC1 senses mitochondria dysfunction.AMPK and HRI are two of the key kinases that signal mitochondria distress to mTORC1, and their loss renders mTORC1 signaling largely resistant to mitochondria dysfunction induced by various inhibitors.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Biotechnology & Applied Microbiology
Alessandro Vinceti, Emre Karakoc, Clare Pacini, Umberto Perron, Riccardo Roberto De Lucia, Mathew J. Garnett, Francesco Iorio
Summary: CRISPR-Cas9 genome-wide screens are crucial for exploring cancer dependencies, with identifying core-fitness genes being essential for assessing therapeutic target safety and understanding tissue-specific genetic diseases. CoRe, an R package, outperforms other tools in identifying reliable and biologically relevant core-fitness genes, aiding in the prioritization of therapeutic targets.
Article
Biotechnology & Applied Microbiology
Friederike Gutmann, Cosimo Jann, Filipa Pereira, Andreas Johansson, Lars M. Steinmetz, Kiran R. Patil
Summary: This study utilizes CRISPR interference in yeast to identify genes modulating fermentative growth in plant hydrolysate and in presence of lignocellulosic toxins, revealing the impact of toxic compounds on these processes. It confirms previous genetic elements and uncovers new targets for designing more robust yeast strains for utilizing lignocellulose hydrolysate as sustainable feedstock, and demonstrates the potential of applying CRISPRi screens to improve industrial fermentation processes.
BIOTECHNOLOGY FOR BIOFUELS
(2021)
Article
Multidisciplinary Sciences
Simon Wisnovsky, Leonhard Mockl, Stacy A. Malaker, Kayvon Pedram, Gaelen T. Hess, Nicholas M. Riley, Melissa A. Gray, Benjamin A. H. Smith, Michael C. Bassik, W. E. Moerner, Carolyn R. Bertozzi
Summary: The study identified key genes required for cell-surface presentation of glycan ligands on leukemia cells using a CRISPRi genomic screening strategy. It revealed a selective interaction between Siglec-7 and the mucin-type glycoprotein CD43, with a specific N-terminal glycopeptide region of CD43 containing clusters of disialylated O-glycan tetrasaccharides forming specific Siglec-7 binding motifs. Knockout or blockade of CD43 in leukemia cells relieves Siglec-7-mediated inhibition of immune killing activity.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Multidisciplinary Sciences
Chao Wang, Xu Feng, Dan Su, Zhen Chen, Shimin Wang, Mengfan Tang, Min Huang, Litong Nie, Huimin Zhang, Siting Li, Ling Yin, Randy L. Johnson, Traver Hart, Junjie Chen
Summary: Cell surface proteins are crucial for cancer development, but their functional analysis is limited. In this study, we used a gene library and CRISPR screens to identify a cell surface tumor suppressor involved in the Hippo pathway.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
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
Cell Biology
Jacob A. Herman, Sonali Arora, Lucas Carter, Jun Zhu, Sue Biggins, Patrick J. Paddison
Summary: In this study, researchers developed a method using CRISPR-Cas9-induced mutations to identify functional regions in protein-coding genes. They applied this method to human mitotic genes and discovered numerous regions required for cell proliferation, including experimentally characterized, homology-predicted, and novel domains.
GENES & DEVELOPMENT
(2022)
Article
Microbiology
Bettina H. Cheung, Arghavan Alisoltani, Travis J. Kochan, Marine Lebrun-Corbin, Sophia H. Nozick, Christopher M. R. Axline, Kelly E. R. Bachta, Egon A. Ozer, Alan R. Hauser
Summary: Gastrointestinal colonization by Klebsiella pneumoniae is a significant risk factor for infection and transmission. This study used transposon insertion sequencing to analyze the genetic requirements for colonization of three clinical strains of K. pneumoniae. The results showed that some genes were required by all strains, while others were strain-specific. This study provides insights into the mechanisms of K. pneumoniae colonization in the mouse GI tract.
Article
Biochemistry & Molecular Biology
Jeong-Min Park, Huimin Zhang, Litong Nie, Chao Wang, Min Huang, Xu Feng, Mengfan Tang, Zhen Chen, Yun Xiong, Namsoo Lee, Siting Li, Ling Yin, Traver Hart, Junjie Chen
Summary: This study reveals that ZATT plays dual roles in ETO treatment, promoting cell survival in a TDP2-independent manner and affecting ETO sensitivity through its interaction with TOP2. It suggests that ZATT is a critical determinant in dictating responses to ETO treatment and targeting ZATT may increase ETO efficacy for cancer therapy.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Biochemistry & Molecular Biology
Bei Wang, Jun-Zhu Chen, Xue-Qun Luo, Guo-Hui Wan, Yan-Lai Tang, Qiao-Ping Wang
Summary: Toxins pose a life-threatening risk to both animals and humans, yet there is a lack of specific antidotes for most toxins. Recent advancements in CRISPR-Cas9 technologies have accelerated the understanding of toxic mechanisms of certain common toxins on hosts from a genome-wide perspective. High-throughput CRISPR screens have enabled the unraveling of complex interactions between specific toxins and their target tissues. This review provides an overview of the latest progress in molecular dissection of toxins' cytotoxicity using genome-wide CRISPR screens, summarizes the essential components for toxin-specific CRISPR screens, and proposes new strategies for future research.
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2022)
Article
Multidisciplinary Sciences
Xiangling Meng, David Yao, Kent Imaizumi, Xiaoyu Chen, Kevin W. Kelley, Noah Reis, Mayuri Vijay Thete, Arpana Arjun McKinney, Shravanti Kulkarni, Georgia Panagiotakos, Michael C. Bassik, Sergiu P. Pasca
Summary: This study uses CRISPR screening and assembloid technology to investigate the involvement of 425 neurodevelopmental disorder genes in human interneuron development. The results identified candidate genes and discovered the displacement of endoplasmic reticulum during interneuron migration, with LNPK gene deletion resulting in abnormal migration.
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
Biochemistry & Molecular Biology
Jin Wei, Mia Madel Alfajaro, Peter C. DeWeirdt, Ruth E. Hanna, William J. Lu-Culligan, Wesley L. Cai, Madison S. Strine, Shang-Min Zhang, Vincent R. Graziano, Cameron O. Schmitz, Jennifer S. Chen, Madeleine C. Mankowski, Renata B. Filler, Neal G. Ravindra, Victor Gasque, Fernando J. de Miguel, Ajinkya Patil, Huacui Chen, Kasopefoluwa Y. Oguntuyo, Laura Abriola, Yulia Surovtseva, Robert C. Orchard, Benhur Lee, Brett D. Lindenbach, Katerina Politi, David van Dijk, Cigall Kadoch, Matthew D. Simon, Qin Yan, John G. Doench, Craig B. Wilen
Summary: Identification of essential host genes for SARS-CoV-2 infection, including ACE2 and Cathepsin L, and the discovery of pro-viral genes and pathways specific to SARS lineage and pan-coronavirus provide potential therapeutic targets and insights into pathogenesis of COVID-19. Small-molecule antagonists of these gene products inhibited SARS-CoV-2 infection across species, highlighting their conserved role in susceptibility to highly pathogenic CoVs.
Article
Biotechnology & Applied Microbiology
Ping Xu, Zhiheng Liu, Ying Liu, Huazheng Ma, Yiyuan Xu, Ying Bao, Shiyou Zhu, Zhongzheng Cao, Zeguang Wu, Zhuo Zhou, Wensheng Wei
Summary: BARBEKO is a DSB-independent, genome-wide CRISPR screening method that leverages CRISPR cytosine base editors to perturb gene start codons or splice sites for KO screening. By integrating with the iBAR strategy, BARBEKO improves screening quality and efficiency, yielding efficient and accurate results with reduced starting cells. Moreover, BARBEKO screens are not impacted by DNA cleavage-induced cytotoxicity in specific cell types, offering a valuable tool to complement current CRISPR-KO screens.
NATURE BIOTECHNOLOGY
(2021)
Article
Cell Biology
Nicholas J. Rossiter, Kimberly S. Huggler, Charles H. Adelmann, Heather R. Keys, Ross W. Soens, David M. Sabatini, Jason R. Cantor
Summary: This study used CRISPR-based screens to reveal the impact of medium composition on gene essentiality in human cells, highlighting variations in essential gene sets in different media and suggesting strategies for using genetic screens to uncover new cancer vulnerabilities and gene-nutrient interactions in human plasma-like medium.
Article
Oncology
Vera Grinkevitch, Mark Wappett, Nyree Crawford, Stacey Price, Andrea Lees, Christopher McCann, Katherine McAllister, Jochen Prehn, Jamie Young, Jess Bateson, Lewis Gallagher, Magali Michaut, Vivek Iyer, Aikaterini Chatzipli, Syd Barthorpe, Daniel Ciznadija, Ido Sloma, Amy Wesa, David A. Tice, Lodewyk Wessels, Mathew Garnett, Daniel B. Longley, Ultan McDermott, Simon S. McDade
Summary: Second-generation TRAIL-R2 agonists face two major clinical challenges: lack of predictive biomarkers and development of resistance. This study identifies caspase-8:FLIP(L) and caspase-8:MCL-1 ratios as potential predictive biomarkers for second-generation TRAIL-R2 agonists, and loss of key effectors like FADD and caspase-8 as likely drivers of clinical resistance in solid tumors.
MOLECULAR CANCER THERAPEUTICS
(2022)
Article
Biochemistry & Molecular Biology
Heather M. Brechbuhl, Mengyu Xie, Etana G. Kopin, Amy L. Han, Kiran Vinod-Paul, Jaime Hagen, Susan Edgerton, Philip Owens, Sharon Sams, Anthony Elias, Carol A. Sartorius, Aik-Choon Tan, Peter Kabos
Summary: The tumor microenvironment plays a crucial role in response and resistance to endocrine therapy in ER-positive breast cancer. The study found that neoadjuvant endocrine therapy alters TME composition, promoting the expansion of less favorable TASC(CDCP1) population associated with TME remodeling and increased immune infiltration supportive of tumor progression.
MOLECULAR CARCINOGENESIS
(2022)
Article
Multidisciplinary Sciences
Marco Napoli, Sarah J. Wu, Bethanie L. Gore, Hussein Abbas, Kyubum Lee, Rahul Checker, Shilpa Dhar, Kimal Rajapakshe, Aik Choon Tan, Min Gyu Lee, Cristian Coarfa, Elsa R. Flores
Summary: Distinct lung stem cells regulated by increment Np63 play a role in the development of both lung adenocarcinoma and squamous cell carcinoma through the regulation of a common landscape of enhancer-associated genes, including BCL9L.
NATURE COMMUNICATIONS
(2022)
Article
Multidisciplinary Sciences
Anna Gogleva, Dimitris Polychronopoulos, Matthias Pfeifer, Vladimir Poroshin, Michael Ughetto, Matthew J. Martin, Hannah Thorpe, Aurelie Bornot, Paul D. Smith, Ben Sidders, Jonathan R. Dry, Miika Ahdesmaki, Ultan McDermott, Eliseo Papa, Krishna C. Bulusu
Summary: Resistance to EGFR inhibitors is a major challenge in the treatment of non-small cell lung cancer. The authors developed a recommender system that ranks genes based on diverse types of evidence, identifying potential mechanisms of EGFR inhibitor resistance.
NATURE COMMUNICATIONS
(2022)
Correction
Multidisciplinary Sciences
Marco Napoli, Sarah J. Wu, Bethanie L. Gore, Hussein A. Abbas, Kyubum Lee, Rahul Checker, Shilpa Dhar, Kimal Rajapakshe, Aik Choon Tan, Min Gyu Lee, Cristian Coarfa, Elsa R. Flores
NATURE COMMUNICATIONS
(2022)
Article
Oncology
Emanuel Goncalves, Rebecca C. Poulos, Zhaoxiang Cai, Syd Barthorpe, Srikanth S. Manda, Natasha Lucas, Alexandra Beck, Daniel Bucio-Noble, Michael Dausmann, Caitlin Hall, Michael Hecker, Jennifer Koh, Howard Lightfoot, Sadia Mahboob, Iman Mali, James Morris, Laura Richardson, Akila J. Seneviratne, Rebecca Shepherd, Erin Sykes, Frances Thomas, Sara Valentini, Steven G. Williams, Yangxiu Wu, Dylan Xavier, Karen L. MacKenzie, Peter G. Hains, Brett Tully, Phillip J. Robinson, Qing Zhong, Mathew J. Garnett, Roger R. Reddel
Summary: The study analyzes the proteomes of multiple cancer cell lines through mass spectrometry and reveals thousands of cancer protein biomarkers that are not significant at the transcript level, demonstrating that the proteome has predictive power for drug response similar to the transcriptome.
Article
Biochemistry & Molecular Biology
Samuel Coleman, Mengyu Xie, Ahmad A. Tarhini, Aik Choon Tan
Summary: Immunotherapy has made significant advancements in the treatment of melanoma, but there is still a need for predictive biomarkers to select patients for immune checkpoint inhibitors (ICIs) therapy. This study evaluated previously published predictive biomarkers based on gene expression signatures and found that biomarkers related to IFN-gamma-responsive genes, T and B cell markers, and chemokines in the tumor immune microenvironment can predict the response to ICIs. The study also showed that these biomarkers are more predictive in on-treatment samples compared to pretreatment samples in metastatic melanoma.
MOLECULAR CARCINOGENESIS
(2023)
Article
Cell Biology
Devin M. Boe, Holly J. Hulsebus, Kevin M. Najarro, Juliet E. Mullen, Hyunmin Kim, Aik Choon Tan, Rachel H. McMahan, Elizabeth J. Kovacs
Summary: As individuals age, alveolar macrophages (AMs) in the lower airways undergo various changes in phenotype and function, exhibiting characteristics of cellular senescence and reduced response to physiological stressors. These age-related alterations, potentially involving glucocorticoid-regulated genes, could interfere with AMs' responses to stressors and contribute to their dysfunction during healthy aging.
JOURNAL OF LEUKOCYTE BIOLOGY
(2022)
Article
Oncology
Sofia Birkealv, Mark Harland, Larissa Satiko Alcantara Sekimoto Matsuyama, Mamun Rashid, Ishan Mehta, Jonathan P. Laye, Kerstin Haase, Tracey Mell, Vivek Iyer, Carla Daniela Robles-Espinoza, Ultan McDermott, Peter van Loo, Marieke L. Kuijjer, Patricia A. Possik, Silvya Stuchi Maria Engler, D. Timothy Bishop, Julia Newton-Bishop, David J. Adams
Summary: This study conducted sequence profiling of 524 American Joint Committee on Cancer Stage I-III primary tumors, revealing recurrent driver mutations, mutually exclusive genetic interactions, and an absence of co-occurring genetic events. By intersecting copy number calls with CRISPR screening data, the transcription factor IRF4 was identified as a melanoma-associated dependency.
JOURNAL OF PATHOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Claudia Buhigas, Anne Y. Warren, Wing-Kit Leung, Hayley C. Whitaker, Hayley J. Luxton, Steve Hawkins, Jonathan Kay, Adam Butler, Yaobo Xu, Dan J. Woodcock, Sue Merson, Fiona M. Frame, Atef Sahli, Federico Abascal, Inigo Martincorena, G. Steven Bova, Christopher S. Foster, Peter Campbell, Norman J. Maitland, David E. Neal, Charlie E. Massie, Andy G. Lynch, Rosalind A. Eeles, Colin S. Cooper, David C. Wedge, Daniel S. Brewer
Summary: This study suggests that cells within normal prostate tissue can expand through mechanisms distinct from cancer, likely originating from stromal cells. Compared to cancer, normal tissue has fewer single nucleotide variants, almost no structural variants or copy number alterations. These findings have significant implications for treatment and early detection approaches.
Article
Cell Biology
Zachary J. Thompson, Jamie K. Teer, Jiannong Li, Zhihua Chen, Eric A. Welsh, Yonghong Zhang, Noura Ayoubi, Zeynep Eroglu, Aik Choon Tan, Keiran S. M. Smalley, Yian Ann Chen
Summary: DRepMel is a Shiny app developed to provide rational combination treatment predictions for melanoma patients using a multi-omics drug repurposing computational approach. It offers robust predictions based on whole exome sequencing and RNA-seq data, and also identifies potential treatment effects on the tumor microenvironment using single-cell RNA-seq data.
Article
Genetics & Heredity
Min Hu, Samuel Coleman, Muhammad Zaki Hidayatullah Fadlullah, Daniel Spakowicz, Christine H. Chung, Aik Choon Tan
Summary: Patients with human papillomavirus-negative head and neck squamous cell carcinoma (HPV-negative HNSCC) have worse outcomes than HPV-positive HNSCC. In our study, we found that microbial signatures can distinguish Hypoxia/Immune phenotypes similar to gene expression signatures in molecularly classified tumor groups. Additionally, we identified three highly-correlated microbes that are crucial for immunotherapy response in immune processes. The co-abundance of these three microbes significantly affects the survival of patients in a molecularly heterogenous group.
Article
Biochemistry & Molecular Biology
Francesco Orlando, Alessandro Romanel, Blanca Trujillo, Michael Sigouros, Daniel Wetterskog, Orsetta Quaini, Gianmarco Leone, Jenny Z. Xiang, Anna Wingate, Scott Tagawa, Anuradha Jayaram, Mark Linch, Mariam Jamal-Hanjani, Charles Swanton, Mark A. Rubin, Alexander W. Wyatt, Himisha Beltran, Gerhardt Attard, Francesca Demichelis
Summary: Sequencing of cell-free DNA in cancer patients' plasma can detect tumor cell genomic alterations and aid clinical decision-making. The novel detection strategy, PCF SELECT, shows improved detection of genomic alterations in samples with low tumor fractions. More extensive pan-genome allelic imbalance was identified in plasma samples from prostate cancer patients.
Meeting Abstract
Oncology
Ahmad A. Tarhini, Aik Choon Tan, Mengyu Xie, Issam El Naqa, Payman Ghasemi Saghand, Donghai Dai, James Lin Chen, Aakrosh Ratan, Martin McCarter, John D. Carpten, Howard Colman, Alexandra Ikeguchi, Abhishek Tripathi, Igor Puzanov, Susanne M. Arnold, Michelle L. Churchman, Patrick Hwu, Jose Conejo-Garcia, William S. Dalton, George J. Weiner
JOURNAL OF CLINICAL ONCOLOGY
(2022)
Meeting Abstract
Oncology
Payman Ghasemi Saghand, Issam El Naqa, Aik Choon Tan, Mengyu Xie, Donghai Dai, James Lin Chen, Aakrosh Ratan, Martin McCarter, John D. Carpten, Harsh Shah, Alexandra Ikeguchi, Abhishek Tripathi, Igor Puzanov, Susanne M. Arnold, Michelle L. Churchman, Patrick Hwu, Jose Conejo-Garcia, William S. Dalton, George J. Weiner, Ahmad A. Tarhini
JOURNAL OF CLINICAL ONCOLOGY
(2022)
