Article
Biochemistry & Molecular Biology
Julian Weischedel, Laurence Higgins, Sally Rogers, Anna Gramalla-Schmitz, Paulina Wyrzykowska, Simone Borgoni, Thomas Maccarthy, Richard Chahwan
Summary: Prokaryotic and eukaryotic adaptive immunity have significant differences, but their gene editing mechanisms via Cas9 and activation-induced deaminase (AID) can complement each other. AID-based editor described in this study is able to recapitulate the full spectrum of genomic and epigenomic editing activity, providing insights into AID biology and improving targeted genomic and epigenomic editing.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Multidisciplinary Sciences
Ines A. M. Barbosa, Rajaraman Gopalakrishnan, Samuele Mercan, Thanos P. Mourikis, Typhaine Martin, Simon Wengert, Caibin Sheng, Fei Ji, Rui Lopes, Judith Knehr, Marc Altorfer, Alicia Lindeman, Carsten Russ, Ulrike Naumann, Javad Golji, Kathleen Sprouffske, Louise Barys, Luca Tordella, Dirk Schubeler, Tobias Schmelzle, Giorgio G. Galli
Summary: YAP activation is a key driver in both malignant pleural mesothelioma and uveal melanoma through engagement of different regulatory elements. Our study reveals lineage-specific features of the YAP regulatory network, providing important insights for designing tailored therapeutic strategies to inhibit YAP signaling across different cancer types.
NATURE COMMUNICATIONS
(2023)
Article
Biotechnology & Applied Microbiology
Kunal Jindal, Mohd Tayyab Adil, Naoto Yamaguchi, Xue Yang, Helen C. Wang, Kenji Kamimoto, Guillermo C. Rivera-Gonzalez, Samantha A. Morris
Summary: This study presents a new method called CellTag-multi, which allows the direct capture of heritable random barcodes expressed as polyadenylated transcripts in single-cell RNA sequencing and single-cell Assay for Transposase Accessible Chromatin using sequencing assays. The CellTag-multi method enables independent clonal tracking of transcriptional and epigenomic cell states and has been validated in studying progenitor cell lineage priming and reprogramming processes. The findings demonstrate the utility of CellTag-multi in revealing gene regulatory changes and providing mechanistic insights into cell fate.
NATURE BIOTECHNOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Ruo-Han Hao, Yan Guo, Chen Wang, Fei Chen, Chen-Xi Di, Shan-Shan Dong, Qi-Long Cao, Jing Guo, Yu Rong, Shi Yao, Dong-Li Zhu, Yi-Xiao Chen, Hao Chen, Tie-Lin Yang
Summary: By comparing and analyzing adipogenesis and osteogenesis in human mesenchymal stem cells, we found that lineage-specific loops can activate gene expression and facilitate cell differentiation through the combination of enhancers and accessible chromatin. We also proposed loop-mediated regulatory networks and identified the controlling factors for adipocyte and osteoblast determination.
CELL DEATH AND DIFFERENTIATION
(2022)
Article
Oncology
Ava Galland, Victor Gourain, Karima Habbas, Yonca Guler, Elisabeth Martin, Claudine Ebel, Manuela Tavian, Laurent Vallat, Marie-Pierre Chenard, Laurent Mauvieux, Jean-Noel Freund, Isabelle Duluc, Claire Domon-Dell
Summary: This study demonstrates the strong oncogenic potential of the homeobox gene CDX2 in the hematopoietic lineage, contrasting with its physiological tumor suppressor activity in the gut. CDX2 protein was shown to bind to and activate the transcription of the human BAMBI promoter, indicating its involvement in perturbation of interactions between leukemia cells and their microenvironment.
MOLECULAR ONCOLOGY
(2021)
Article
Oncology
Dong-Liang Lin, Li-Li Wang, Peng Zhao, Wen-Wen Ran, Wei Wang, Long-Xiao Zhang, Ming Han, Hua Bao, Kaihua Liu, Xue Wu, Yang Shao, Xiao-Ming Xing
Summary: The number of extra-appendiceal GCA in Chinese patients was underestimated. GCA can be seen as a distinct morphological, immunohistochemical, transcriptomic, and immunological entity. The classic low-grade component of GCA and the immunoreactivity for neuroendocrine markers are key points to diagnosing GCA.
FRONTIERS IN ONCOLOGY
(2021)
Article
Medicine, Research & Experimental
Jingjing Wang, Xu Zhu, Lin Dang, Hongmei Jiang, Ying Xie, Xin Li, Jing Guo, Yixuan Wang, Ziyi Peng, Mengqi Wang, Jingya Wang, Sheng Wang, Qian Li, Yafei Wang, Qiang Wang, Lingqun Ye, Lirong Zhang, Zhiqiang Liu
Summary: The t(4;14) chromosomal translocation drives high expression of NSD2 and plays important roles in MM evolution and progression. HRP2 downregulation is associated with poor response and worse outcomes in PIs treatment, and its suppression promotes cell survival and restricts ER stress by increasing H3K27me3 levels.
JOURNAL OF CLINICAL INVESTIGATION
(2022)
Article
Multidisciplinary Sciences
Raisa A. Reyes-Castro, Shin-Yu Chen, Jacob Seemann, Samrat T. Kundu, Don L. Gibbons, Swathi Arur
Summary: The KRAS/ERK pathway phosphorylates DICER1, leading to its nuclear translocation, and phosphomimetic Dicer1 promotes tumorigenesis in mice. However, the mechanisms by which phospho-DICER1 regulates tumor progression are not fully understood. In this study, we discovered that phosphorylated nuclear DICER1 (phospho-nuclear DICER1) promotes late-stage tumor progression in mice with oncogenic Kras, independent of microRNAs (miRNAs) and epithelial-to-mesenchymal transition (EMT). Our findings suggest that phospho-nuclear DICER1 plays a role in lineage reprogramming of tumor cells to mediate lung cancer progression.
Article
Biochemistry & Molecular Biology
Yukino Ogura, Norihiko Ohbayashi, Yasunori Kanaho, Atsushi Kawaguchi, Yuji Funakoshi
Summary: In tumors, TRE17 regulates cell invasion by modulating the levels of CD147 at the cell surface, promoting tumor cell invasion by preventing CD147 degradation, enhancing matrix metalloproteinase synthesis and matrix degradation.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Huajie Song, Jianqun Wang, Xiaojing Wang, Boling Yuan, Dan Li, Anpei Hu, Yanhua Guo, Shuang Cai, Shikai Jin, Yi Zhou, Qilan Li, Guo Chen, Haiyang Gao, Liduan Zheng, Qiangsong Tong
Summary: This study identifies a peptide called sPEP1, encoded by HNF4A-AS1, in neuroblastoma tumor tissues and cells. sPEP1 promotes self-renewal and aggressiveness of neuroblastoma stem cells by interacting with other proteins and regulating gene transcription.
Article
Biotechnology & Applied Microbiology
Hernan Gonzalez-King, Sandra Tejedor, Maria Ciria, Marta Gil-Barrachina, Mario Soriano-Navarro, Rafael Sanchez-Sanchez, Pilar Sepulveda, Nahuel A. Garcia
Summary: This study investigates the involvement of small extracellular vesicles (SEVs) in functional Notch signaling and finds that SEVs in breast cancer cells can regulate Notch signal transduction, leading to increased invasiveness and proliferation of breast cancer cells.
CANCER GENE THERAPY
(2022)
Article
Biotechnology & Applied Microbiology
Zhi Zou, Yongguo Zhao, Li Zhang
Summary: This study identified and compared oleosin genes in Euphorbiaceae species, revealing lineage-specific evolution patterns. The presence of oleosin ortholog groups suggests conservation dating back to the Malpighiales ancestor, with whole-genome duplications driving family expansion in cassava and rubber tree. Seed-predominant expression and structure divergence of paralogous pairs indicate functional diversity within the oleosin family.
Article
Biochemistry & Molecular Biology
Maria V. V. Guijarro, Akbar Nawab, Peter Dib, Sandra Burkett, Xiaoping Luo, Michael Feely, Elham Nasri, Robert P. P. Seifert, Frederic J. J. Kaye, Maria Zajac-Kaye
Summary: We found that elevated expression of TYMS has oncogenic properties and promotes tumorigenesis, suggesting cooperation with sequential somatic mutations. In this study, we demonstrate the cooperation between ectopic expression of human TYMS and loss of Ink4a/Arf, a commonly mutated event in human cancer. Our data shows that deregulated TYMS expression accelerates tumorigenesis and metastasis in an Ink4a/Arf null background. In addition, downregulation of TYMS decreases cell proliferation and sensitizes tumor cells to chemotherapy, while depletion of TYMS reduces tumor incidence, delays tumor progression, and prolongs survival.
Article
Multidisciplinary Sciences
Zhongbo Chen, David Zhang, Regina H. Reynolds, Emil K. Gustavsson, Sonia Garcia-Ruiz, Karishma D'Sa, Aine Fairbrother-Browne, Jana Vandrovcova, John Hardy, Henry Houlden, Sarah A. Gagliano Taliun, Juan Botia, Mina Ryten
Summary: Knowledge of genomic features specific to the human lineage may provide insights into brain-related diseases, with certain regions playing a potential role in both brain development and neurological disease.
NATURE COMMUNICATIONS
(2021)
Article
Pathology
Linyuan Wang, Bejan J. Saeedi, Zaid Mahdi, Alyssa Krasinskas, Brian Robinson
Summary: This study evaluated the distribution of KRAS mutations in adenocarcinomas of the gastrointestinal tract and pancreatobiliary system. The results showed regional variation in the frequency of KRAS mutations, with pancreatic adenocarcinoma having the highest frequency. Specific KRAS mutation patterns were observed in different primary sites. KRAS mutational analysis can be useful in determining the site of origin in gastrointestinal adenocarcinomas with histologic and immunohistochemical overlap.
Article
Clinical Neurology
Parthiv Haldipur, Silvia Bernardo, Kimberly A. Aldinger, Tarika Sivakumar, Jake Millman, Alexandria H. Sjoboen, Derek Dang, Danilo Dubocanin, Mei Deng, Andrew E. Timms, Brian D. Davis, Jasmine T. Plummer, Kshitij Mankad, Ozgur Oztekin, Lucia Manganaro, Fabien Guimiot, Homa Adle-Biassette, Rosa Russo, Joseph R. Siebert, Debora Kidron, Giulia Petrilli, Nathalie Roux, Ferechte Razavi, Ian A. Glass, Cira Di Gioia, Evelina Silvestri, Kathleen J. Millen
Summary: Dandy-Walker malformation (DWM) and Cerebellar vermis hypoplasia (CVH) are common cerebellar malformations diagnosed through ultrasound and MRI. Histopathological analysis showed reduced foliation and inferior vermian hypoplasia in DWM cases. Disruption of the rhombic lip, with reduced proliferation and altered vasculature, is key in the pathogenesis of DWM.
ACTA NEUROPATHOLOGICA
(2021)
Article
Oncology
Jin-Fen Xiao, Ley-Fang Kua, Ling-Wen Ding, Qiao-Yang Sun, Khine Nyein Myint, Xiu-Rong Chia, Nachiyappan Venkatachalam, Xinyi Loh, Jason E. Duex, Vanessa Neang, Siqin Zhou, Ying Li, Henry Yang, H. Phillip Koeffler, Dan Theodorescu
Summary: KDM6A depletion promotes cell migration and transformation in breast cells, reduces sensitivity to therapeutic agents, induces TGF beta secretion, and suppresses cytotoxic gene expression. KDM6A deficiency and TGF beta treatment drive tumor progression, leading to disorganized acinar structures and expression profiles associated with epithelial-to-mesenchymal transition and metastasis.
MOLECULAR CANCER RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Tiago C. Silva, Juan Young, Eden R. Martin, X. Steven Chen, Lily Wang
Summary: MethReg is an R/Bioconductor package that analyzes DNA methylation and gene expression data, along with transcription factor binding information, to evaluate and annotate CpG sites with high regulatory potential. The software plays an important role in studying the regulatory roles of DNA methylation in complex diseases.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Immunology
Jasmine T. Plummer, Deisy Contreras, Wenjuan Zhang, Aleksandra Binek, Ruan Zhang, Felipe Dezem, Stephanie S. Chen, Brian D. Davis, Jorge Sincuir Martinez, Aleksandr Stotland, Simion Kreimer, Elias Makhoul, Saleh Heneidi, Celeste Eno, Bongha Shin, Anders H. Berg, Susan Cheng, Stanley C. Jordan, Eric Vail, Jennifer E. Van Eyk, Margie A. Morgan
Summary: This study investigates the characteristics of the epsilon variant of SARS-CoV-2 and its impact on the human immune system. The results show that patients carrying the epsilon variant have a higher risk of mortality, but do not have an increased risk of hospitalization. Furthermore, cells infected with the epsilon virus are more sensitive to neutralizing antibodies, but vaccinated individuals show a slightly protective response. Compared to non-epsilon variants, the epsilon variant has higher infectivity but lower virulence due to the down-regulation of viral processing pathways. These findings highlight the importance of immune responses to new variants, and both vaccinated and unvaccinated individuals need to be vigilant.
CLINICAL INFECTIOUS DISEASES
(2022)
Article
Gastroenterology & Hepatology
Alex B. Blair, Jianxin Wang, John Davelaar, Andrew Baker, Keyu Li, Nan Niu, Junke Wang, Yingkuan Shao, Vanessa Funes, Pan Li, Jonathan A. Pachter, Daniel C. Maneval, Felipe Dezem, Jasmine Plummer, Keith Syson Chan, Jun Gong, Andrew E. Hendifar, Stephen J. Pandol, Richard Burkhart, Yuqing Zhang, Lei Zheng, Arsen Osipov
Summary: This study identifies the synergistic effects of targeting both intracellular and extracellular components within the PDAC stroma, and supports the potential of testing anti-CXCR4 antibody in combination with FAKi as a PDAC treatment strategy.
Article
Oncology
Nicole Gull, Michelle R. Jones, Pei-Chen Peng, Simon G. Coetzee, Tiago C. Silva, Jasmine T. Plummer, Alberto Luiz P. Reyes, Brian D. Davis, Stephanie S. Chen, Kate Lawrenson, Jenny Lester, Christine Walsh, Bobbie J. Rimel, Andrew J. Li, Ilana Cass, Yonatan Berg, John-Paul B. Govindavari, Joanna K. L. Rutgers, Benjamin P. Berman, Beth Y. Karlan, Simon A. Gayther
Summary: Global DNA methylation may not play a significant role in recurrence and chemoresistance of high grade serous ovarian cancer (HGSOC). The methylation and gene expression programs established in the primary tumor are conserved throughout the progression of the disease.
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
(2022)
Article
Oncology
Amber A. DeVries, Joe Dennis, Jonathan P. Tyrer, Pei-Chen Peng, Simon G. Coetzee, Alberto L. Reyes, Jasmine T. Plummer, Brian D. Davis, Stephanie S. Chen, Felipe Segato Dezem, Katja K. H. Aben, Hoda Anton-Culver, Natalia N. Antonenkova, Matthias W. Beckmann, Alicia Beeghly-Fadiel, Andrew Berchuck, Natalia Bogdanova, Nadja Bogdanova-Markov, James D. Brenton, Ralf Butzow, Ian Campbell, Jenny Chang-Claude, Georgia Chenevix-Trench, Linda S. Cook, Anna DeFazio, Jennifer A. Doherty, Thilo Dork, Diana M. Eccles, A. Heather Eliassen, Peter A. Fasching, Renee T. Fortner, Graham G. Giles, Ellen L. Goode, Marc T. Goodman, Jacek Gronwald, Niclas Hakansson, Michelle A. T. Hildebrandt, Chad Huff, David G. Huntsman, Allan Jensen, Siddhartha Kar, Beth Y. Karlan, Elza K. Khusnutdinova, Lambertus A. Kiemeney, Susanne K. Kjaer, Jolanta Kupryjanczyk, Marilyne Labrie, Diether Lambrechts, Nhu D. Le, Jan Lubinski, Taymaa May, Usha Menon, Roger L. Milne, Francesmary Modugno, Alvaro N. Monteiro, Kirsten B. Moysich, Kunle Odunsi, Hakan Olsson, Celeste L. Pearce, Tanja Pejovic, Susan J. Ramus, Elio Riboli, Marjorie J. Riggan, Isabelle Romieu, Dale P. Sandler, Joellen M. Schildkraut, V. Wendy Setiawan, Weiva Sieh, Honglin Song, Rebecca Sutphen, Kathryn L. Terry, Pamela J. Thompson, Linda Titus, Shelley S. Tworoger, Els Van Nieuwenhuysen, Digna Velez Edwards, Penelope M. Webb, Nicolas Wentzensen, Alice S. Whittemore, Alicja Wolk, Anna H. Wu, Argyrios Ziogas, Matthew L. Freedman, Kate Lawrenson, Paul D. P. Pharoah, Douglas F. Easton, Simon A. Gayther, Michelle R. Jones
Summary: This study identified risk associations between copy number variants (CNVs) and epithelial ovarian cancer (EOC), particularly for the BRCA1, BRCA2, and RAD51C genes. The study also found enrichment of CNVs at known EOC risk loci and functional biofeatures in EOC-related cell types. These findings suggest that CNVs may play a potentially pathogenic role in the development of EOC.
JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE
(2022)
Article
Virology
Shabir A. Bhat, Tomohiro Shibata, Matthew Leong, Jasmine Plummer, Eric Vail, Zakir Khan
Summary: This study used RNA-sequencing to analyze the transcriptional response in the upper respiratory tract of COVID-19 patients, and found that severe cases showed an upregulated early type I interferon response and pronounced induction of interferon stimulated genes (ISGs).
Article
Chemistry, Multidisciplinary
Pei Huang, Lingsheng Jiang, Hui Pan, Lingwen Ding, Bo Zhou, Mengyao Zhao, Jianhua Zou, Benhao Li, Meiwei Qi, Hongzhang Deng, Yongfeng Zhou, Xiaoyuan Chen
Summary: Researchers synthesized a new polymer for mRNA delivery, which showed no inflammatory side effects in vivo and successfully delivered mRNA cancer vaccines, resulting in robust anti-tumor cellular immune response.
ADVANCED MATERIALS
(2023)
Article
Oncology
Xue-Bin Ran, Ling-Wen Ding, Qiao-Yang Sun, Henry Yang, Jonathan W. Said, Lao Zhentang, Vikas Madan, Pushkar Dakle, Jin-Fen Xiao, Xinyi Loh, Ying Li, Liang Xu, Xiao-Qiang Xiang, Ling-Zhi Wang, Boon Cher Goh, De-Chen Lin, Wee Joo Chng, Soo-Yong Tan, Sudhakar Jha, H. Phillip Koeffler
Summary: Despite the limited response rate of immune checkpoint blockade therapy, targeting RNA decay machinery by silencing XRN1 can sensitize tumor cells to immunotherapy by activating IFN signaling and the viral defense pathway. XRN1 depletion triggers aberrant RNA-mediated IFN signaling and has the potential to be effective in multiple types of cancers. These findings provide a molecular rationale for developing XRN1 inhibitors and combining them with cancer immunotherapy.
Article
Multidisciplinary Sciences
Tal Falick Michaeli, Ofra Sabag, Rimma Fok, Batia Azria, Jonathan Monin, Yuval Nevo, Yuval Gielchinsky, Benjamin P. Berman, Howard Cedar, Yehudit Bergman
Summary: Muscle injury activates stem cells and changes their methylation pattern to facilitate myocyte differentiation. This change can also occur in satellite cells from other muscles and in muscle stem cells (MuSCs) of female animals following pregnancy.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Medicine, Research & Experimental
Win Lwin Thuya, Li Ren Kong, Nicholas L. Syn, Ling -Wen Ding, Esther Sok Hwee Cheow, Regina Tong Xin Wong, Tingting Wang, Robby Miguel Wen-Jing Goh, Hongyan Song, Migara K. Jayasinghe, Minh T. N. Le, Jian Cheng Hu, Wei-Peng Yong, Soo-Chin Lee, Andrea Li-Ann Wong, Gautam Sethi, Huynh The Hung, Paul Chi-Lui Ho, Jean-Paul Thiery, Siu Kwan Sze, Tiannan Guo, Ross A. Soo, Henry Yang, Yaw Chyn Lim, Lingzhi Wang, Boon-Cher Goh
Summary: This study reveals that the cargo protein FAM3C carried by tumor-released extracellular vesicles (EVs) can enhance the growth and metastatic potential of lung cancer cells. FAM3C interacts with RalA protein to activate the Src/Stat3 signaling pathway, promoting oncogenicity. This finding provides a new target for lung cancer therapy.
Article
Neurosciences
Shuo Chen, Yuzhou Chang, Liangping Li, Diana Acosta, Yang Li, Qi Guo, Cankun Wang, Emir Turkes, Cody Morrison, Dominic Julian, Mark E. Hester, Douglas W. Scharre, Chintda Santiskulvong, Sarah XueYing Song, Jasmine T. Plummer, Geidy E. Serrano, Thomas G. Beach, Karen E. Duff, Qin Ma, Hongjun Fu
Summary: This study utilizes the 10x Visium platform to investigate the transcriptomic profile of the human middle temporal gyrus (MTG) in early Alzheimer's disease (AD). The results identify differentially expressed genes (DEGs) and reveal the important role of cell-cell communication in AD pathology. The findings provide insights into the complex architecture and the response of neuronal and glial cells to AD pathology in this susceptible brain region.
ACTA NEUROPATHOLOGICA COMMUNICATIONS
(2022)
Article
Oncology
Gideon Ze Lin Tan, Sai Mun Leong, Yu Jin, Chik Hong Kuick, Jeremy Joon Keat Chee, San Zeng Low, Ling-Wen Ding, He Cheng, Diana Lim, Susan Swee-Shan Hue
Summary: In this study, we analyzed the expression of microRNAs in endometrial carcinomas and found differential expression profiles among different subtypes and molecular subtypes. These findings may have implications for the development of diagnostic and prognostic tools for endometrial carcinoma.
Article
Biotechnology & Applied Microbiology
Efrat Katsman, Shari Orlanski, Filippo Martignano, Ilana Fox-Fisher, Ruth Shemer, Yuval Dor, Aviad Zick, Amir Eden, Iacopo Petrini, Silvestro G. Conticello, Benjamin P. Berman
Summary: The Oxford Nanopore (ONT) platform provides portable and rapid genome sequencing, and its ability to natively profile DNA methylation without complex sample processing is attractive for point-of-care real-time sequencing. It has been shown that ONT shallow whole-genome sequencing can detect copy number alterations (CNAs) and other cancer-related changes, making it a potential powerful tool for liquid biopsy.