Nucleic Acids Research: TATDN2 resolution of R-loops is required for survival of BRCA1-mutant cancer cells (Gupta, Pertsemlidis, Bishop, & Sung Labs)

November 20, 2023

Aruna S Jaiswal, Arijit Dutta, Gayathri Srinivasan, Yaxia Yuan, Daohong Zhou, Montaser Shaheen, Doraid T Sadideen, Austin Kirby, Elizabeth A Williamson, Yogesh K Gupta, Shaun K Olsen, Mingjiang Xu, Eva Loranc, Pramiti Mukhopadhyay, Alexander Pertsemlidis, Alexander J R Bishop, Patrick Sung, Jac A Nickoloff, Robert Hromas Abstract BRCA1-deficient cells have increased IRE1 RNase, which degrades multiple microRNAs. Reconstituting expression of one of these, miR-4638–5p, resulted in synthetic lethality in BRCA1-deficient cancer cells. We found that miR-4638-5p represses [...]

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 [...]

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 [...]

NAR Cancer: The 3D Chromatin Landscape of Rhabdomyosarcoma (Ignatius Lab)

June 16, 2023

  Meng Wang, Prethish Sreenivas, Benjamin D Sunkel, Long Wang, Myron Ignatius, Benjamin Z Stanton Abstract Rhabdomyosarcoma (RMS) is a pediatric soft tissue cancer with a lack of precision therapy options for patients. We hypothesized that with a general paucity of known mutations in RMS, chromatin structural driving mechanisms are essential for tumor proliferation. Thus, we carried out high-depth in situ Hi-C in [...]

Nature: Break-induced replication orchestrates resection-dependent template switching (Sung)

June 15, 2023

Tianpeng Zhang, Yashpal Rawal, Haoyang Jiang, Youngho Kwon, Patrick Sung & Roger A. Greenberg Abstract Break-induced telomere synthesis (BITS) is a RAD51-independent form of break-induced replication that contributes to the alternative lengthening of telomeres1,2. This homology-directed repair mechanism utilizes a minimal replisome comprising proliferating cell nuclear antigen (PCNA) and DNA polymerase-δ to execute conservative DNA repair [...]

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, [...]

Cell Reports: EWSR1 Maintains Centromere Identity (Kitagawa & Houghton labs)

May 30, 2023

Risa Kitagawa 1, Yohei Niikura 1 2, Argentina Becker 1 3, Peter J. Houghton 1, Katsumi Kitagawa 1 4 Highlights EWSR1 is required to maintain CENP-A at the centromere in interphase cells EWSR1 binds to CENP-A through the SYGQ2 region, important for phase separation EWSR1 binds to R loops in vitro through its RNA-recognition motif (RRM) EWSR1 protects CENP-A in the centromeric chromatin by binding to centromeric RNAs Summary The centromere is essential [...]

Clinical Cancer Research: Phase II Investigation of TVB-2640 (Denifanstat)with Bevacizumabin Patients with First Relapse High-Grade Astrocytoma (Chen)

May 24, 2023

William Kelly 1, Adolfo Enrique Diaz Duque 1,Joel Michalek 2, Brandon Konkel 3,L aura Caflisch 3, Yidong Chen 2,Sarath Chand Pathuri 1,Vinu Madhusudanannair-Kunnuparampil 4, John Floyd II 5,and Andrew Brenner 1 ABSTRACT Purpose: Glioblastoma represents the most common primary brain tumor. Although antiangiogenics are used in the recurrent setting, they do not prolong survival. Glioblastoma [...]

Advanced Science: Epigenetic Control of Translation Checkpoint and Tumor Progression via RUVBL1-EEF1A1 Axis (Bishop)

April 26, 2023

Mingli Li, Lu Yang, Anthony K. N. Chan, Sheela Pangeni Pokharel, Qiao Liu, Nicole Mattson, Xiaobao Xu, Wen-Han Chang, Kazuya Miyashita, Priyanka Singh, Leisi Zhang, Maggie Li, Jun Wu, Jinhui Wang, Bryan Chen, Lai N. Chan, Jaewoong Lee, Xu Hannah Zhang, Steven T. Rosen, Markus Müschen, Jun Qi, Jianjun Chen, Kevin Hiom, Alexander J. R. Bishop, Chun-Wei Chen … See fewer authors  First published: 19 April 2023   Abstract Epigenetic dysregulation is reported in multiple cancers, including Ewing sarcoma (EwS). However, [...]

Cell Reports: Nitric Oxide Suppression by Secreted Frizzled-Related Protein 2 Drives Retinoblastoma (Shiio & Houghton Labs)

March 17, 2023

Panneerselvam Jayabal 1, Fuchun Zhou 1, Xiuye Ma 1, Kathryn M. Bondra 1, Barron Blackman 1, Susan T. Weintraub 2 3, Yidong Chen 1 3 4, Patricia Chévez-Barrios 5, Peter J. Houghton 1 3 6, Brenda Gallie 7, Yuzuru Shiio 1 2 3 8 Highlights The autocrine signaling mediated by SFRP2 drives retinoblastoma SFRP2 signaling suppresses NO production and maintains retinoblastoma growth CXADR serves as the receptor for SFRP2 Targeting SFRP2 results in NO production and suppression of retinoblastoma growth Summary Retinoblastoma is a cancer of the infant retina primarily driven by the loss of [...]