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
Multidisciplinary Sciences
Connor Yanchus, Kristen L. Drucker, Thomas M. Kollmeyer, Ricky Tsai, Warren Winick-Ng, Minggao Liang, Ahmad Malik, Judy Pawling, Silvana B. De Lorenzo, Asma Ali, Paul A. Decker, Matt L. Kosel, Arijit Panda, Khalid N. Al-Zahrani, Lingyan Jiang, Jared W. L. Browning, Chris Lowden, Michael Geuenich, J. Javier Hernandez, Jessica T. Gosio, Musaddeque Ahmed Section, Sampath Kumar Loganathan Paragraph, Jacob Berman, Daniel Trcka, Kulandaimanuvel Antony Michealraj, Jerome Fortin, Brittany Carson, Ethan W. Hollingsworth, Sandra Jacinto, Parisa Mazrooei, Lily Zhou, Andrew Elia, Mathieu Lupien, Housheng Hansen He, Daniel J. Murphy, Liguo Wang, Alexej Abyzov, James W. Dennis, Philipp G. Maass, Kieran Campbell, Michael D. Wilson, Daniel H. Lachance, Margaret Wrensch, John Wiencke, Tak Mak, Len A. Pennacchio, Diane E. Dickel Section Section, Axel Visel, Jeffrey Wrana, Michael D. Taylor, Gelareh Zadeh, Peter Dirks, Jeanette E. Eckel-Passow, Liliana Attisano, Ana Pombo, Cristiane M. Ida, Evgeny Z. Kvon, Robert B. Jenkins, Daniel Schramek
Summary: This study reveals the causal relationship between the single-nucleotide polymorphism rs55705857 and the increased risk of low-grade glioma (LGG). The research also identifies the molecular pathways associated with this polymorphism. The risk allele disrupts the binding of OCT2/4 and increases the expression of Myc. In a mouse model, mutating the rs55705857 locus accelerates tumor development and increases disease penetrance.
Article
Biochemistry & Molecular Biology
Jenny L. Kerschner, Alekh Paranjapye, Nirbhayaditya Vaghela, Michael D. Wilson, Ann Harris
Summary: Transcription of the cystic fibrosis transmembrane conductance regulator (CFTR) gene is regulated by both ubiquitous and cell-type selective cis-regulatory elements (CREs). Deletion of the airway-selective -35 kb enhancer in lung epithelial cells disrupts normal enhancer-promoter looping at the CFTR locus and greatly reduces CFTR expression. Relocating the functional core of this enhancer to an ectopic site in intron 1 leads to increased CFTR expression, although not to wild-type levels.
Article
Multidisciplinary Sciences
Ryan J. Smith, Minggao Liang, Adrian Kwan Ho Loe, Theodora Yung, Ji-Eun Kim, Matthew Hudson, Michael D. Wilson, Tae-Hee Kim
Summary: In this study, the researchers found that gastrointestinal mesenchymal cells control epithelial fate and function through Polycomb Repressive Complex 2-mediated chromatin bivalency. The results highlight the importance of mesenchymal-epithelial crosstalk in gut development and stem cell homeostasis.
NATURE COMMUNICATIONS
(2023)
Article
Chemistry, Multidisciplinary
Abdalla M. Abdrabou, Bill T. Duong, Kangfu Chen, Randy Singh Atwal, Mahmoud Labib, Sichun Lin, Stephane Angers, Shana O. Kelley
Summary: Genome-wide loss-of-function screens are important for identifying novel genetic regulators of intracellular proteins. However, studying the changes in protein expression profile can be challenging due to localization differences. This study introduces nuPRISM, a microfluidics chip for large-scale isolated nuclei sorting, that enables rapid genome-wide loss-of-function screens for intranuclear targets.
ACS CENTRAL SCIENCE
(2022)
Article
Biochemistry & Molecular Biology
Ahmad N. Nabhan, Joshua D. Webster, Jarret J. Adams, Levi Blazer, Christine Everrett, Celine Eidenschenk, Alexander Arlantico, Isabel Fleming, Hans D. Brightbill, Paul J. Wolters, Zora Modrusan, Somasekar Seshagiri, Stephane Anders, Sachdev S. Sidhu, Kim Newton, Joseph R. Arron, Vishva M. Dixit
Summary: Wnt ligands control stem cell activity by oligomerizing different combinations of Fzd and Lrp5/6 receptors. In the lung alveoli, epithelial, endothelial, and stromal cells express distinct Fzd receptors. Fzd5 is specifically required for alveolar epithelial stem cell activity, while fibroblasts use different Fzd receptors. Canonical Wnt signaling in alveolar epithelial stem cells can be activated by either Fzd5 or non-canonical Fzd6, providing a potential strategy for promoting regeneration during lung injury.
Article
Chemistry, Multidisciplinary
Zongjie Wang, Hansen Wang, Sichun Lin, Mahmoud Labib, Sharif Ahmed, Jagotamoy Das, Stephane Angers, Edward H. Sargent, Shana O. Kelley
Summary: Nanoneedles are effective in delivering biomolecules to cells, but the mechanisms underlying cell-nanoneedle interactions are not well understood. In this study, we developed a new method to generate nanoneedles, confirmed their cargo delivery capability, and investigated the genetic factors involved in the process. Our results showed that the nanoneedles disrupted cell membranes, increased the expression of cell-cell junction proteins, and downregulated transcriptional factors of the NF kappa B pathway. This disturbance caused most cells to be trapped in the G2 phase, where endocytosis activities are highest. This system provides a new model for studying cell interactions with high-aspect-ratio materials.
Article
Biochemistry & Molecular Biology
Nevraj S. Kejiou, Lena Ilan, Stefan Aigner, Enching Luo, Tori Tonn, Hakan Ozadam, Muyoung Lee, Gregory B. Cole, Ines Rabano, Nishani Rajakulendran, Brian A. Yee, Hamed S. Najafabadi, Trevor F. Moraes, Stephane Angers, Gene W. Yeo, Can Cenik, Alexander F. Palazzo
Summary: In this study, the researchers investigated the factors that regulate compartment specific mRNA translation in human cells. They found that the glycolytic enzyme Pyruvate Kinase M (PKM) interacts with polysomes and influences mRNA translation, and this interaction is regulated by ADP levels. Further experiments indicated that PKM binds to mRNA sequences downstream of lysine- and glutamate-enriched tracts and causes translational stalling near these sequences. The recruitment of PKM to polysomes depends on poly-ADP ribosylation activity, suggesting a link between cellular metabolism and mRNA translation.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Multidisciplinary Sciences
Deivid C. Rodrigues, Marat Mufteev, Kyoko E. Yuki, Ashrut Narula, Wei Wei, Alina Piekna, Jiajie Liu, Peter Pasceri, Olivia S. Rissland, Michael D. Wilson, James Ellis
Summary: This study measured transcription rate and mRNA half-life changes in RTT patient-derived neurons and reinterpreted nuclear and whole-cell RNAseq from Mecp2 mice. The results showed that dysregulation of genes in RTT is caused by changes in transcription rate or half-life, but genes are buffered when both change. In addition, three dinucleotide frequencies were found to be better predictors of transcription rate changes than CA and CG. MicroRNA and RNA-binding Protein (RBP) motifs were enriched in the 3'UTRs of genes with half-life changes, while nuclear RBP motifs were enriched in buffered genes with increased transcription rate. The study revealed post-transcriptional mechanisms in neurodevelopmental disorders caused by mutations in transcriptional modulator genes.
NATURE COMMUNICATIONS
(2023)
Article
Multidisciplinary Sciences
Xian Wang, Zheyuan Gong, Tiancong Wang, Junhui Law, Xin Chen, Siyi Wanggou, Jintian Wang, Binbin Ying, Michelle Francisco, Weifan Dong, Yi Xiong, Jerry J. Fan, Graham MacLeod, Stephane Angers, Xuejun Li, Peter B. Dirks, Xinyu Liu, Xi Huang, Yu Sun
Summary: Researchers have developed a mechanical approach using magnetic carbon nanotubes to treat chemoresistant glioblastoma (GBM). GBM cells can internalize the nanotubes and their mobilization by rotating magnetic fields leads to cell death. In vivo studies show that spatiotemporally controlled release of the nanotubes inhibits GBM growth. Functionalizing the nanotubes with an antibody that recognizes GBM cell surface antigen CD44 enhances their recognition of cancer cells and improves therapeutic efficacy. This study establishes the use of magnetic carbon nanotubes as a treatment option for GBM.
Article
Radiology, Nuclear Medicine & Medical Imaging
Amanda J. Boyle, Zhongli Cai, Siobhan O'Brien, Jennifer Crick, Stephane Angers, Raymond M. Reilly
Summary: This study aimed to compare the radiobiological effectiveness of [64Cu]Cu-NOTA-panitumumab F(ab')2 and [177Lu]Lu-NOTA-panitumumab F(ab')2 radioimmunotherapy (RIT) agents with XRT in decreasing the clonogenic survival fraction (SF) of EGFR-positive human PDAC cell lines. The results showed that both RIT agents were less effective than XRT in reducing the SF of PDAC cells.
NUCLEAR MEDICINE AND BIOLOGY
(2023)
Article
Nutrition & Dietetics
Joe Eun Son, Jay-Young Jo, San Kim, Min Ju Park, Yerin Lee, Seong Shil Park, Shin Young Park, Su Myung Jung, Sung Keun Jung, Ji Yeon Kim, Sanguine Byun
Summary: Rice bran, a by-product of rice milling, is rich in bioactive molecules and has health-promoting properties in improving metabolic conditions. This study aimed to optimize the extraction conditions of rice bran extract (RBE) and validate its impact on lipid metabolism. The optimized RBE showed significant benefits in reducing weight gain, hyperlipidemia, and hepatosteatosis in mouse models. The study also discovered that the administration of optimized RBE activated AMPK and inhibited STAT3, crucial players in liver lipid metabolism. Overall, optimized RBE holds promise as a dietary intervention against hyperlipidemia and hepatosteatosis.
Article
Multidisciplinary Sciences
Lingling Zhang, Md. Abedin, Ha-Neul Jo, Jacklyn Levey, Quynh Chau Dinh, Zhe Chen, Stephane Angers, Harald J. Junge
Summary: Norrin (NDP) and WNT7A/B stimulate the FZD4-LRP5/6 complex to induce beta-catenin-dependent signaling in endothelial cells (ECs), thus maintaining the blood-brain and blood-retina barrier (BBB, BRB). A tetravalent antibody modality, F4L5.13, was found to have agonist activities in Tspan12-/- mice, leading to the alleviation of BRB defects, retinal hypovascularization, and restoration of neural function. Administration of F4L5.13 rapidly and substantially restores the BRB in a genetic model of impaired maintenance.
Article
Genetics & Heredity
Dustin J. Sokolowski, Jedid Ahn, Lauren Erdman, Huayun Hou, Kai Ellis, Liangxi Wang, Anna Goldenberg, Michael D. Wilson
Summary: Differential gene expression analysis using RNA sequencing data is an important method for biological discoveries. We developed a powerful pipeline to recompute differential expression gene lists from various databases and built a tool called DEET to help users interact with these lists, identify relevant studies, and generate hypotheses for further research.
NAR GENOMICS AND BIOINFORMATICS
(2023)
Article
Biochemistry & Molecular Biology
Tanja Sack, Piriththiv Dhavarasa, Daniel Szames, Siobhan O'Brien, Stephane Angers, Shana O. Kelley
Summary: Comparing to nuclear DNA repair mechanisms, the characterization of mtDNA repair mechanisms is difficult due to the challenge of specifically addressing mitochondrial damage. This study uses an mtDNA-damaging agent in combination with CRISPR/Cas9 screening to identify genes essential for mtDNA damage response and confirms the responsiveness of WRNIP1 to mtDNA damage for the first time. The study also reveals the mitochondrial role of WRNIP1 in innate immune signaling and nuclear genome maintenance.
ACS CHEMICAL BIOLOGY
(2023)
