PNAS: Phase separation of the oncogenic fusion protein EWS::FLI1 is modulated by its DNA-binding domain (Libich & Bishop Labs)

May 16, 2025

 Emily E. Selig  Erich J. Sohn  Aiola Stoja, Alma K. Moreno-Romero, Shivani Akula, Xiaoping Xu, Alexander J. R. Bishop, and David S. Libich Significance The oncogenic fusion protein, EWS::FLI1, responsible for more than 85% of Ewing sarcoma tumors, combines the transactivation domain from EWS and the DNA-binding domain (DBD) from Friend leukemia integration 1 (FLI1). The fusion impacts the function of wild-type EWS and drives oncogenesis via [...]

Cell Reports: Distinct roles of the two BRCA2 DNA-binding domains in DNA damage repair and replication fork preservation (Sung, Libich Labs)

May 7, 2025

 Francisco E. Neal1,2 ∙ Wenjing Li1 ∙ Mollie E. Uhrig3,4 ∙ Jeffrey N. Katz1,2 ∙ Shahrez Syed1,2 ∙ Neelam Sharma3 ∙ Arijit Dutta1,2,8 ∙ Sandeep Burma1,5 ∙ Robert Hromas6 ∙ Alexander V. Mazin1 ∙ Eloise Dray1 ∙ David S. Libich1,2 ∙ Shaun K. Olsen1,2 ∙ Elizabeth V. Wasmuth1,2 ∙ Weixing Zhao1,2 ∙ Claus S. Sørensen7 Highlights BRCA2 OB-fold DNA-binding domain has specificity for ssDNA BRCA2 C-terminal DNA-binding domain has specificity for dsDNA OB-fold DNA-binding domain is needed for DNA repair and replication fork protection C-terminal DNA-binding domain functions primarily in replication fork protection Summary Homologous recombination (HR) removes DNA double-strand breaks [...]

Trends in Molecular Medicine: The RB protein: more than a sentry of cell cycle entry (Sung Lab)

May 1, 2025

 Pulari U. Thangavelu1,11 ∙ Cheng-Yu Lin1,11 ∙ Farzaneh Forouz2 ∙ Kozo Tanaka3 ∙ Eloïse Dray4,5,6 ∙ Pascal H.G. Duijf7,8,9,10 pascal.duijf@unisa.edu.au Highlights The retinoblastoma protein (RB) signal transduction pathway suppresses tumor development and is impaired in most cancers. RB pathway disruption in tumors promotes a broad range of malignant properties, such as cancer-associated blood vessel formation, metastasis, inflammation, immune evasion, cell survival, and metabolic reprogramming, as well as genomic instability. Impaired RB pathway [...]

Nature Communications: Epigenetic silencing of DNA sensing pathway by FOXM1 blocks stress ligand-dependent antitumor immunity and immune memory (Rao, Chen, Zheng, Sung Labs et al)

April 29, 2025

 Santosh Timilsina, Jian Yu Huang, Nourhan Abdelfattah, Daisy Medina, Deepika Singh, Shahad Abdulsahib, Panneerdoss Subbarayalu, Trong Phat Do, Prabhakar Pitta Venkata, Saif Nirzhor, Jack Prochnau, Mukund Bhandari, Siyuan Zheng, Yidong Chen, Gang Huang, Neelam Mukherjee, Robert Hromas, Patrick Sung, Virginia Kaklamani, Ratna Vadlamudi, Nu Zhang & Manjeet K. Rao Abstract The interplay between tumor cells and [...]

Clinical Cancer Research: Update on Cancer and Central Nervous System Tumor Surveillance in Pediatric NF2-, SMARCB1-, and LZTR1-Related Schwannomatosis (Tomlinson)

April 15, 2025

 Melissa R. Perrino Marjolijn C.J. Jongmans Gail E. Tomlinson Mary-Louise C. Greer Sarah R. Scollon Sarah G. Mitchell Jordan R. Hansford Kris Ann P. Schultz Wendy K. Kohlmann Jennifer M. Kalish Suzanne P. MacFarland Anirban Das Kara N. Maxwell Stefan M. Pfister Rosanna Weksberg Orli Michaeli Uri Tabori Gina M. Ney Philip J. Lupo Jack [...]

IScience: Dissection of tumoral niches using spatial transcriptomics and deep learning (Chen)

April 15, 2025

 Karla Paniagua1 ∙ Yu-Fang Jin1 ∙ Yidong Chen2,3 ∙ Shou-Jiang Gao4,5 ∙ Yufei Huang4,6,7 ∙ Mario Flores1,8 mario.flores@utsa.edu Highlights •TG-ME integrates transformer and GraphVAE for cancer niche analysis •Achieves superior clustering and profiling tumor microenvironments •Leverages multimodal data for comprehensive TME analysis •Enables precise identification of tumor microenvironment composition Summary This study introduces TG-ME, an innovative computational framework that integrates transformer with graph variational autoencoder (GraphVAE) models for dissection of tumoral niches [...]

Structure: Structural insights into the assembly and regulation of 2′-O RNA methylation by SARS-CoV-2 nsp16/nsp10 (Gupta Lab)

April 14, 2025

 Anurag Misra 1 2, R. Rahisuddin 1 2, Manish Parihar 1, Shailee Arya 1, Thiruselvam Viswanathan 1 2, Nathaniel Jackson 3, Shan Qi 1 2, Siu-Hong Chan 4, Reuben S. Harris 2 5, Luis Martinez-Sobrido 3, Yogesh K. Gupta 1 2 6 Highlights SARS-CoV-2 nsp16/nsp10 oligomerizes on capped mRNA for efficient 2′-O methylation An aromatic zipper in nsp16 modulate oligomerization and methylation N-terminus of nsp10 is required for efficient 2′-O methylation A nucleotide-binding pocket on the backside of nsp16 modulates the 2′-O methylation Summary 2′-O-ribose methylation of viral RNA's first transcribed base (adenine or A1 in SARS-CoV-2) [...]

Molecular Oncology: Hijacking the BAF complex: the mechanistic interplay of ARID1A and EWS::FLI1 in Ewing sarcoma (Libich Lab)

April 10, 2025

 Erich J. Sohn, David S. Libich Abstract Ewing sarcoma, an aggressive pediatric cancer, is driven by the EWS::FLI1 fusion protein, which disrupts gene expression by hijacking the BAF chromatin remodeling complex. Central to this mechanism is the formation of biomolecular condensates, mediated by the prion-like domains (PrLDs) of EWS and ARID1A, a core BAF subunit. ARID1A serves [...]

Biomolecular NMR Assignments: The 1H, 15N and 13C backbone resonance assignments of the N-terminal (1-149) domain of Serpine mRNA Binding Protein 1 (SERBP1) (Libich Lab)

March 31, 2025

 Antoine Baudin1, Hoang H Dinh1, Xiaoping Xu1, David S Libich2 Abstract Serpine mRNA-Binding Protein 1 (SERBP1) is an RNA-binding protein implicated in diverse cellular functions, including translational regulation, tumor progression, and stress response. It interacts with ribosomal subunits, RNA, and proteins involved in stress granules, contributing to processes such as phase separation and epigenetic regulation. Recent studies have [...]