A5053607742- RNA Research and Splicing
- Nuclear Structure and Function
- RNA and protein synthesis mechanisms
- Monoclonal and Polyclonal Antibodies Research
- SARS-CoV-2 and COVID-19 Research
- RNA modifications and cancer
- Bacteriophages and microbial interactions
- Enzyme Structure and Function
- Glycosylation and Glycoproteins Research
- Ubiquitin and proteasome pathways
- Graphite, nuclear technology, radiation studies
- Fungal and yeast genetics research
- Advanced Proteomics Techniques and Applications
- vaccines and immunoinformatics approaches
- Mass Spectrometry Techniques and Applications
- Genomics and Chromatin Dynamics
- Animal Virus Infections Studies
- Advanced Electron Microscopy Techniques and Applications
- Radioactive element chemistry and processing
- Microbial Metabolic Engineering and Bioproduction
- interferon and immune responses
- Immunotherapy and Immune Responses
- Extracellular vesicles in disease
- Photosynthetic Processes and Mechanisms
- NF-κB Signaling Pathways
State Key Laboratory of Respiratory Disease
2025
Guangzhou Medical University
2025
Icahn School of Medicine at Mount Sinai
2022-2024
Zhejiang University
2021-2024
Rockefeller University
2014-2024
Hohai University
2024
Huaihua University
2024
University of Pittsburgh
2017-2023
Carnegie Mellon University
2020-2022
Xuzhou Central Hospital
2022
Nanobodies that neutralize Monoclonal antibodies bind to the spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) show therapeutic promise but must be produced in mammalian cells and need delivered intravenously. By contrast, single-domain called nanobodies can bacteria or yeast, their stability may enable aerosol delivery. Two papers now report tightly efficiently SARS-CoV-2 cells. Schoof et al. screened a yeast surface display synthetic Xiang anti-spike by llama....
Nuclear pore complexes (NPCs) mediate the nucleocytoplasmic transport of macromolecules. Here we provide a structure isolated yeast NPC in which inner ring is resolved by cryo-EM at sub-nanometer resolution to show how flexible connectors tie together different structural and functional layers. These may be targets for phosphorylation regulated disassembly cells with an open mitosis. Moreover, some nucleoporin pairs factors have similar interaction motifs, suggests evolutionary mechanistic...
Globally, there is an urgency to develop effective, low-cost therapeutic interventions for coronavirus disease 2019 (COVID-19). We previously generated the stable and ultrapotent homotrimeric Pittsburgh inhalable Nanobody 21 (PiN-21). Using Syrian hamsters that model moderate severe COVID-19 disease, we demonstrate high efficacy of PiN-21 prevent treat SARS-CoV-2 infection. Intranasal delivery at 0.6 mg/kg protects infected animals from weight loss substantially reduces viral burdens in both...
Significance This study shows that Fragile X mental retardation protein (FMRP) promotes messenger RNA (mRNA)-dependent recombination via facilitating ten-eleven translocation 1 (TET1)-mediated mRNA methyl-5-cytosine (m5C) demethylation. Loss of FMRP leads to damage induced m5C and R-loop accumulation at sites active transcription, defective repair, increased radiosensitivity tumor cells. FMRP-dependent demethylation resolving during DNA repair are important for completion the maintenance...
The nuclear pore complex (NPC) is the sole mediator of nucleocytoplasmic transport. Despite great advances in understanding its conserved core architecture, peripheral regions can exhibit considerable variation within and between species. One such structure cage-like basket. crucial roles mRNA surveillance chromatin organization, an architectural has remained elusive. Using in-cell cryo-electron tomography subtomogram analysis, we explored NPC's structural variations basket across fungi...
A novel cellular protein, Abl-interactor-1 (Abi-1), which specifically interacts with the carboxy-terminal region of Abl oncoproteins, has been identified in a mouse leukemia cell line. The protein exhibits sequence similarity to homeotic genes, contains several polyproline stretches, and includes src homology 3 (SH3) domain at its very carboxyl terminus that is required for binding proteins. abi-1 gene mapped chromosome 2 genetically closely linked c-abl locus. widely expressed mouse,...
Most cellular processes are orchestrated by macromolecular complexes. However, structural elucidation of these endogenous complexes can be challenging because they frequently contain large numbers proteins, compositionally and morphologically heterogeneous, dynamic, often low abundance in the cell. Here, we present a strategy for characterization such that has at its center chemical cross-linking with mass spectrometric readout. In this strategy, isolate using highly optimized sample...
Transforming growth factor-beta-activated kinase 1 (TAK1) plays an essential role in the tumor necrosis factor alpha (TNFalpha)- and interleukin-1beta (IL-1beta)-induced IkappaB (IKK)/nuclear factor-kappaB (NF-kappaB) c-Jun N-terminal (JNK)/activator protein (AP-1) activation. Here we report that TNFalpha IL-1beta induce Lys(63)-linked TAK1 polyubiquitination at Lys(158) residue within domain. Tumor receptor-associated factors 2 6 (TRAF2 -6) act as ubiquitin E3 ligases to mediate vivo vitro....
Actively transcribed regions of the genome are protected by transcription-coupled DNA repair mechanisms, including homologous recombination (TC-HR). Here we used reactive oxygen species (ROS) to induce and characterize TC-HR at a locus in human cells. As canonical HR, requires RAD51. However, localization RAD51 damage sites during does not require BRCA1 BRCA2, but relies on RAD52 Cockayne Syndrome Protein B (CSB). During TC-HR, is recruited CSB through an acidic domain. turn R loops, which...
The number of publications in the field chemical cross-linking combined with mass spectrometry (XL-MS) to derive constraints for protein three-dimensional structure modeling and probe protein-protein interactions has increased during last years. As technique is now becoming routine vitro vivo applications proteomics structural biology there a pressing need define protocols as well data analysis reporting formats. Such consensus formats should become accepted be shown lead reproducible...
Interventions against variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are urgently needed. Stable and potent nanobodies (Nbs) that target the receptor binding domain (RBD) SARS-CoV-2 spike promising therapeutics. However, it is unknown if Nbs broadly neutralize circulating variants. We found RBD highly resistant to concern (VOCs). High-resolution cryoelectron microscopy determination eight Nb-bound structures reveals multiple neutralizing epitopes clustered into...
Glioblastoma is a highly malignant and incurable brain tumor characterized by intrinsic adaptive resistance to immunotherapies. However, how glioma cells induce immunosuppression escape immunosurveillance remains poorly understood. Here, we find upregulation of cancer-intrinsic Chitinase-3-like-1 (CHI3L1) signaling modulating an immunosuppressive microenvironment reprogramming tumor-associated macrophages (TAMs). Mechanistically, CHI3L1 binding with Galectin-3 (Gal3) selectively promotes TAM...
Ubiquitination and deubiquitination of receptor-interacting protein 1 (RIP1) play an important role in the positive negative regulation tumor necrosis factor α (TNFα)-induced nuclear κB (NF-κB) activation. Using a combination functional genomic proteomic approaches, we have identified ubiquitin-specific peptidase 21 (USP21) as deubiquitinase for RIP1. USP21 is constitutively associated with RIP1 deubiquitinates vitro vivo. Notably, knockdown HeLa cells enhances TNFα-induced ubiquitination,...
Abstract Early eukaryotic ribosome biogenesis involves large multi-protein complexes, which co-transcriptionally associate with pre-ribosomal RNA to form the small subunit processome. The precise mechanisms by two of largest complexes—UtpA and UtpB—interact nascent are poorly understood. Here, we combined biochemical structural biology approaches ensembles RNA–protein cross-linking data elucidate essential functions both complexes. We show that UtpA contains a composite RNA-binding site...
The TORC1 signaling pathway plays a major role in the control of cell growth and response to stress. Here we demonstrate that SEA complex physically interacts with is an important regulator its activity. During nitrogen starvation, deletions components lead Tor1 kinase delocalization, defects autophagy, vacuolar fragmentation. inactivation, via deprivation or rapamycin treatment, changes cellular levels members. We used affinity purification chemical cross-linking generate data for...