ACS Medicinal Chemistry Letters: Identification and Exploration of a Series of SARS-Cov-2 MPro Cyano-Based Inhibitors Revealing Ortho-Substitution Effects within the P3 Biphenyl Group (Olsen)

November 10, 2025

 Emma Clyde-Allen Mikołaj Zmudzinski Mohammad Afsar Ciyana James Anindita Nayak Digant Nayak Priscila dos Santos Bury Dirk Jochmans Johann Neyts Christopher J. Scott Shaun K. Olsen Marcin Drag Rich Williams* Abstract Starting from a simple scaffold hopping exercise based on our previous exploration of cysteine protease inhibitors against legumain, compound 6a was identified as a starting point [...]

Molecular Medicine: Selective inhibition of BRAF and CRAF sensitizes NF1-deficient malignant peripheral nerve sheath tumors to MEK inhibitors (Zheng, Kitagawa Lab)

October 2, 2025

       Jiawan Wang, Arnab Sarkar, Natalia Garcia, Lindy Zhang, Ana Calizo, Alla Lisok, Katia Campos, Funan He, Nishanth Punjaala, Teresa Marple, Kai Pollard, Siyuan Zheng, Calixto-Hope G. Lucas, Vesselina G. Cooke, Christine A. Pratilas & Angelina V. Vaseva Abstract Background Treatment for patients with malignant peripheral nerve sheath tumors (MPNST) is an unmet clinical [...]

Nature Structural & Molecular Biology: Cryo-EM structures reveal the molecular mechanism of SUMO E1–E2 thioester transfer (Olsen Lab, Sung Lab)

September 26, 2025

 Anindita Nayak, Digant Nayak, Lijia Jia, Eliza A. Ruben, Suryavathi Viswanadhapalli, Priscila dos Santos Bury, Khaled Mohamed Nassar, Corey H. Yu, Anna A. Tumanova, Caleb M. Stratton, Pirouz Ebadi, Dmitri N. Ivanov, Patrick Sung, Ratna K. Vadlamudi, Elizabeth V. Wasmuth & Shaun K. Olsen Abstract Post-translational modification of proteins by SUMO (small ubiquitin-like modifier) regulates fundamental [...]

BioRxiv: Phosphoregulation of RAD51AP1 function in homology-directed repair (Sung Lab)

September 22, 2025

 Neelam Sharma, Mollie Uhrig, Youngho Kwon, Patrick Sung,  Claudia Wiese ABSTRACT Homology-directed DNA repair (HDR) is critical for genome stability and tumor suppression. HDR is initiated by the RAD51 single-stranded (ss)DNA nucleoprotein filament which conducts the homology search and invades a homologous DNA template, creating a displacement-loop (D-loop). The RAD51 filament is assisted in these processes by several proteins. One [...]

Protein Science: Molecular basis of EWS interdomain self-association and its role in condensate formation (Libich Lab)

September 22, 2025

 Erich J. Sohn, Kandarp A. Sojitra, Leticia Rodrigues, Xiaoping Xu, Bess Frost, Jeetain Mittal, David S. Libich Abstract Ewing sarcoma, the second most common pediatric bone and soft tissue cancer, is caused by the aberrant fusion of the RNA-binding protein EWS (EWS) low-complexity domain (EWSLCD) to the DNA-binding domain of the transcription factor friend leukemia integration 1 (FLI1). The resulting fusion, [...]

Trends in Biochemical Sciences: E3 Ubiquitin Ligases in Signaling, Disease, and Therapeutics (Olsen)

September 15, 2025

 Pirouz Ebadi 1, Caleb M Stratton 1, Shaun K Olsen 2 Abstract The ubiquitin-proteasome system (UPS) is a central regulator of protein turnover and signaling, with E3 ubiquitin ligases conferring substrate specificity and chain-type control. Recent advances have revealed new mechanistic classes of E3 ligases and expanded our understanding of their roles in disease, including cancer, neurodegeneration, and immune dysfunction. [...]

Aging Cell: Inhibition of Hippo Signaling Through Ablation of Lats1 and Lats2 Protects Against Cognitive Decline in 5xFAD Mice via Increasing Neuronal Resilience Against Ferroptosis (Zheng)

September 10, 2025

 Robert C. Evans, Nawab John Dar, Liuji Chen, Ren Na, Jason C. O'Connor, Jing Jiang, Siyuan Zheng, Qitao Ran ABSTRACT The Hippo signaling pathway is a key regulator of cell growth and cell survival, and hyperactivation of the Hippo pathway has been implicated in neurodegenerative diseases such as Huntington's disease. However, the role of Hippo signaling in Alzheimer's disease (AD) remains unclear. [...]

Expert Opinion on Therapeutic Targets: Rhabdomyosarcoma: development of molecular therapeutics under the microscope (Houghton)

August 15, 2025

 Peter J. Houghton Mary-Ann Bjornsti ABSTRACT Rhabdomyosarcoma (RMS), predominantly diagnosed in children, represents 3% of the pediatric solid tumors. RMS has characteristics of skeletal muscle, although the cell of origin remains controversial. Cytotoxic therapeutics, radiation treatment, and surgery remain the standard of care; however, outcomes for advanced disease have not changed for several decades. Major [...]

Biochemistry: The Spliceosomal Peptidyl Prolyl Isomerase Like 1 Interacts with the Low-Complexity Domain of the RNA Binding Protein EWS Modulating Its Phase Separation Behavior (Libich Lab)

August 8, 2025

 George L Parra 1, Erich J Sohn 1, Xiaoping Xu 1, David S Libich 1 Abstract RNA-binding protein EWS, a member of the FET (FUS, EWS, TAF15) family, contributes to mRNA biogenesis through roles in transcription, splicing, and RNA transport. Despite evidence linking EWS to spliceosomal complexes, its interactions with spliceosome-associated cyclophilins remain unclear. Here, we describe the first structural and biochemical [...]