A5100325877- Cancer Immunotherapy and Biomarkers
- Immunotherapy and Immune Responses
- Chromatin Remodeling and Cancer
- Mechanisms of cancer metastasis
- CAR-T cell therapy research
- Genetics and Neurodevelopmental Disorders
- Neuroscience and Neuropharmacology Research
- Immune Cell Function and Interaction
- RNA and protein synthesis mechanisms
- Ion channel regulation and function
- Peptidase Inhibition and Analysis
- SARS-CoV-2 and COVID-19 Research
- Lipid Membrane Structure and Behavior
- Monoclonal and Polyclonal Antibodies Research
- Receptor Mechanisms and Signaling
- Cancer Mechanisms and Therapy
- RNA modifications and cancer
- Neuroendocrine Tumor Research Advances
- Neurobiology and Insect Physiology Research
- Estrogen and related hormone effects
- RNA regulation and disease
- Ferroptosis and cancer prognosis
- Porphyrin Metabolism and Disorders
- Prostate Cancer Treatment and Research
- Cellular transport and secretion
Amgen (United States)
2023-2024
Sichuan University
2024
West China Hospital of Sichuan University
2024
Nanchang University
2024
First Affiliated Hospital of Nanchang University
2024
Fudan University
2023
University of California, San Francisco
2016-2022
ShanghaiTech University
2020-2022
Universidad Católica de Santa Fe
2021-2022
Molecular Biology Consortium
2020-2021
The COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a grave threat to public health and the global economy. SARS-CoV-2 closely related more lethal but less transmissible coronaviruses SARS-CoV-1 Middle East (MERS-CoV). Here, we have carried out comparative viral-human protein-protein interaction viral protein localization analyses for all three viruses. Subsequent functional genetic screening identified host factors that functionally impinge on...
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus enters host cells via an interaction between its Spike protein and the cell receptor angiotensin-converting enzyme (ACE2). By screening a yeast surface-displayed library of synthetic nanobody sequences, we developed nanobodies that disrupt ACE2. Cryo-electron microscopy (cryo-EM) revealed one nanobody, Nb6, binds in fully inactive conformation with binding domains locked into their inaccessible down state, incapable...
Transport dependent on context Transporter proteins move substrates across a membrane, often coupling this activity to cellular ion concentration gradients. For neurotransmitter transporters, which reside in synaptic vesicles that fuse with the plasma membrane after an action potential, transport needs be regulated so they do not pump out neurotransmitters vesicle fusion. Using cryo–electron microscopy, Li et al. determined structure of vesicular glutamate transporter from rat unveils some...
Abstract The SARS-CoV-2 protein Nsp2 has been implicated in a wide range of viral processes, but its exact functions, and the structural basis those remain unknown. Here, we report an atomic model for full-length obtained by combining cryo-electron microscopy with deep learning-based structure prediction from AlphaFold2. resulting reveals highly-conserved zinc ion-binding site, suggesting role RNA binding. Mapping emerging mutations variants on shows potential host-Nsp2 interaction regions....
ABSTRACT Without an effective prophylactic solution, infections from SARS-CoV-2 continue to rise worldwide with devastating health and economic costs. gains entry into host cells via interaction between its Spike protein the cell receptor angiotensin converting enzyme 2 (ACE2). Disruption of this confers potent neutralization viral entry, providing avenue for vaccine design therapeutic antibodies. Here, we develop single-domain antibodies (nanobodies) that potently disrupt ACE2. By screening...
Abstract Muscarinic acetylcholine receptors (mAChRs) respond to the neurotransmitter and play important roles in human nervous system. receptor 4 (M4R) is a promising drug target for treating neurological mental disorders, such as Alzheimer’s disease schizophrenia. However, lack of understanding on M4R’s activation by subtype selective agonists hinders its therapeutic applications. Here, we report structural characterization M4R allosteric agonist, compound-110, well agonist iperoxo positive...
The tumor-associated antigen STEAP1 is a potential therapeutic target that expressed in most prostate tumors and at increased levels metastatic castration-resistant cancer (mCRPC). We developed STEAP1-targeted XmAb 2+1 T-cell engager (TCE) molecule, AMG 509 (also designated xaluritamig), designed to redirect T cells kill express STEAP1. mediates potent cell-dependent cytotoxicity of cell lines vitro promotes tumor regression xenograft syngeneic mouse models vivo. avidity-driven activity...
Opioid therapeutics are excellent analgesics, whose utility is compromised by dependence. Morphine (1) and its clinically relevant derivatives such as OxyContin (2), Vicodin (3), Dilaudid (4) "biased" agonists at the μ opioid receptor (OR), wherein they engage G protein signaling but poorly β-arrestin endocytic machinery. In contrast, endorphins, endogenous peptide for ORs, potent show reduced liability tolerance dependence, both pathways "balanced" agonists. We set out to determine if...
Abstract Chronic lymphocytic leukemia/small lymphoma (CLL/SLL) has different epidemiology in Chinese vs. Western patients, but there are few studies of CLL/SLL large populations patients. ALPINE is a global phase 3 trial investigating Bruton tyrosine kinase inhibitors zanubrutinib ibrutinib to treat relapsed/refractory (R/R) CLL/SLL. Here we report results from the subgroup Adults with R/R were randomized 1:1 receive (160 mg twice-daily) or (420 once-daily) until disease progression...
Abstract Heparan sulfate (HS) is degraded in lysosome by a series of glycosidases. Before the glycosidases can act, terminal glucosamine HS must be acetylated integral lysosomal membrane enzyme heparan-α-glucosaminide N -acetyltransferase (HGSNAT). Mutations HGSNAT cause accumulation and consequently mucopolysaccharidosis IIIC, devastating storage disease characterized progressive neurological deterioration early death where no treatment available. catalyzes unique transmembrane acetylation...
Prostate cancer is a prevalent malignancy, often diagnosed at advanced stages and associated with poor prognosis. Genistein, soybean isoflavone, has demonstrated antitumor effects against castration-resistant prostate in vivo. Our results indicate that genistein effectively downregulates the expression of key enzymes involved de novo synthesis pathway, namely AKR1C3, SRD5A2, CYP11A1, 3βHSD, thus blocking androgen CRPC cells. Additionally, inhibits activation nuclear translocation AR....
The ancient protein TSPO (translocator 18kD) is found in all kingdoms and was originally identified as a binding site of benzodiazepine drugs. Its physiological function remains unclear, although porphyrins are conserved ligands. Several crystal structures bacterial nuclear magnetic resonance mouse form have revealed monomer dimer configurations, but there been no reports with ligand. Here, we present the first X-ray Rhodobacter sphaeroides ligand bound. Two different variants (substituting...
The SARS-CoV-2 protein Nsp2 has been implicated in a wide range of viral processes, but its exact functions, and the structural basis those remain unknown. Here, we report an atomic model for full-length obtained by combining cryo-electron microscopy with deep learning-based structure prediction from AlphaFold2. resulting reveals highly-conserved zinc ion-binding site, suggesting role RNA binding. Mapping emerging mutations variants on shows potential host-Nsp2 interaction regions. Using...
Rationale: Sunitinib is a small-molecule tyrosine kinase inhibitor associated with the side-effect of liver injury. The impaired cell type in and hepatotoxicity mechanisms still unclear. Methods: Spatial metabolomics, transmission electron microscopy, immunofluorescence co-staining, isolation bile duct cells sinusoidal endothelial (LSECs) were used to evaluate zonated sunitinib. Farnesoid X receptor (FXR) conditional knockout mice, metagenomics analysis, bacteria clearance, bacterial...
Abstract Alternative translation is an important cellular mechanism contributing to the generation of proteins and diversity protein functions. Instead studying individual cases, we systematically analyzed alteration subcellular location domain formation by alternative translational initiation in eukaryotes. The results revealed that 85.7% events generated biological diversity, attributed different localizations distinct contents isoforms. Analysis isoelectric point values most N‐terminal...
Human muscarinic receptor M4 belongs to the class A subfamily of G-protein-coupled receptors (GPCRs). has emerged as an attractive drug target for treatment Alzheimer's disease and schizophrenia. Recent results showed that M4-mediated cholinergic transmission is related motor symptoms in Parkinson's disease. Selective ligand design five acetylcholine (mAchR) subtypes currently remains challenging owing high sequence structural similarity their orthosteric binding pockets. In order obtain...