Research Paper

Molecular Cell: DICER Ribonuclease Removes Harmful R-Loops (Sung)

October 18, 2023

Lola P. Camino 1 2 4, Arijit Dutta 3 4, Sonia Barroso 1 2, Carmen Pérez-Calero 1 2, Jeffrey N. Katz 3, María García-Rubio 1 2, Patrick Sung 3, Belén Gómez-González 1 2, Andrés Aguilera 1 2 5 Highlights •DICER RNase activity mediates R-loop processing in vitro and in cells •DICER binds R-loops readily but not DNA-RNA hybrids •DICER cleaves the RNA moiety of DNA-RNA hybrids within R-loop structures •DICER overexpression counteracts harmful nuclear DNA-RNA hybrids Summary R-loops, consisting of a DNA-RNA hybrid and a displaced DNA strand, threaten genome integrity. To counteract [...]

Cancers: Dysregulation of Type I Interferon (IFN-I) Signaling: A Potential Contributor to Racial Disparity in Hepatocellular Carcinoma (HCC) (Lai)

September 12, 2023

            Saranya Chidambaranathan Reghupaty 1,†,Sadia Kanwal 2, Rachel G. Mendoza 3, Eva Davis 4,Haiwen Li 2, Zhao Lai 5, Mikhail G. Dozmorov 6 ,Milton Omar Faison 7, Rafat Ali Siddiqui 2, *Devanand Sarkar 8,* Simple Summary Hepatocellular carcinoma (HCC) is the most common primary liver cancer arising from the liver [...]

Embro Reports: Loss of BRD4 induces cell senescence in HSC/HPCs by deregulating histone H3 clipping (Chen)

September 5, 2023

Abstract Bromodomain-containing protein 4 (BRD4) is overexpressed and functionally implicated in various myeloid malignancies. However, the role of BRD4 in normal hematopoiesis remains largely unknown. Here, utilizing an inducible Brd4 knockout mouse model, we find that deletion of Brd4 (Brd4Δ/Δ) in the hematopoietic system impairs hematopoietic stem cell (HSC) self-renewal and differentiation, which associates with cell cycle arrest and [...]

Science Reports: Sex-dependent differences in the genomic profile of lingual sensory neurons in naïve and tongue-tumor bearing mice (Chen, Lai)

August 14, 2023

Tarek Ibrahim, Ping Wu, Li-Ju Wang, Chang Fang-Mei, Josue Murillo, Jaclyn Merlo, Sergey S. Shein, Alexei V. Tumanov, Zhao Lai, Korri Weldon, Yidong Chen & Shivani Ruparel Abstract Mechanisms of sex-dependent orofacial pain are widely understudied. A significant gap in knowledge exists about the comprehensive regulation of tissue-specific trigeminal sensory neurons in diseased states of both [...]

Nucleic Acids Research: TLK1-Mediated RAD54 Phosphorylation Spatio-Temporally Regulates Homologous Recombination Repair (Chen, Sung)

July 13, 2023

Ishita Ghosh, Youngho Kwon, Aida Badamchi Shabestari, Rupesh Chikhale, Jing Chen, Claudia Wiese, Patrick Sung, Arrigo De Benedetti Abstract Environmental agents like ionizing radiation (IR) and chemotherapeutic drugs can cause severe damage to the DNA, often in the form of double-strand breaks (DSBs). Remaining unrepaired, DSBs can lead to chromosomal rearrangements and cell death. One major error-free pathway to repair DSBs is homologous [...]

Bioinformatics Advances: DepLink: an R Shiny app to systematically link genetic and pharmacologic dependencies of cancer (Zheng, Houghton, & Chen Labs)

June 27, 2023

Tapsya Nayak, Li-Ju Wang, Michael Ning, Gabriela Rubannelsonkumar, Eric Jin, Siyuan Zheng, Peter J Houghton, Yufei Huang, Yu-Chiao Chiu, Yidong Chen Abstract Motivation Large-scale genetic and pharmacologic dependency maps are generated to reveal genetic vulnerabilities and drug sensitivities of cancer. However, user-friendly software is needed to link such maps systematically. Results Here, we present DepLink, a web server to identify genetic and pharmacologic perturbations [...]

Nature: Structural Insights into BCDX2 Complex Function in Homologous Recombination (Sung Lab)

June 22, 2023

Yashpal Rawal, Lijia Jia, Aviv Meir, Shuo Zhou, Hardeep Kaur, Eliza A. Ruben, Youngho Kwon, Kara A. Bernstein, Maria Jasin, Alexander B. Taylor, Sandeep Burma, Robert Hromas, Alexander V. Mazin, Weixing Zhao, Daohong Zhou, Elizabeth V. Wasmuth, Eric C. Greene, Patrick Sung & Shaun K. Olsen Abstract Homologous recombination (HR) fulfils a pivotal role in the [...]

RNA Biology: The Paralogues MAGOH and MAGOHB are Oncogenic Factors in High-Grade Gliomas and Safeguard the Splicing of Cell Division and Cell Cycle Genes (Penalva Lab)

June 9, 2023

Rodrigo A. S. Barreiro, Gabriela D. A. Guardia, Fabiana M. Meliso, Xiufen Lei, Wei-Qing Li, Andre Savio, Martin Fellermeyer, Helena B. Conceição, Rafael L. V. Mercuri, Tesha Landry, Mei Qiao, Lorea Blazquez, Jernej Ule, Luiz O.F. Penalva & Pedro A. F. Galante ABSTRACT The exon junction complex (EJC) plays key roles throughout the lifespan of [...]

Journal of Clinical Oncology: The Childhood Cancer Data Initiative: Using the Power of Data to Learn From and Improve Outcomes for Every Child and Young Adult With Pediatric Cancer (Aune Co-author)

June 5, 2023

Joseph A. Flores-Toro  , PhD1; Subhashini Jagu  , PhD1; Gregory T. Armstrong, MD, MSCE2; David F. Arons, JD3; Gregory J. Aune, MD, PhD4; Stephen J. Chanock  , MD1; Douglas S. Hawkins  , MD5; Allison Heath  , PhD6; Lee J. Helman  , MD7; Katherine A. Janeway  , MD, MMSc8; Jason E. Levine  , MD1; Ellyn Miller, [...]

ELife: Defining function of wild-type and three patient specific TP53 mutations in a zebrafish model of embryonal rhabdomyosarcoma (Ignatius Lab, Houghton Lab, Libich Lab, Chen, Tomlinson)

June 2, 2023

Jiangfei Chen Kunal Baxi Amanda E Lipsitt Nicole Rae Hensch Long Wang Prethish Sreenivas Paulomi Modi Xiang Ru Zhao Antoine Baudin Daniel G Robledo Abhik Bandyopadhyay Aaron Sugalski Anil K Challa Dias Kurmashev Andrea R Gilbert Gail E Tomlinson Peter Houghton Yidong Chen Madeline N Hayes Eleanor Y Chen David S Libich Myron S Ignatius [...]