A5017785423- Asthma and respiratory diseases
- Receptor Mechanisms and Signaling
- interferon and immune responses
- Immune cells in cancer
- Pediatric health and respiratory diseases
- Immune Cell Function and Interaction
- Monoclonal and Polyclonal Antibodies Research
- Chemokine receptors and signaling
- Inhalation and Respiratory Drug Delivery
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Immune Response and Inflammation
- Neurobiology and Insect Physiology Research
- Pneumonia and Respiratory Infections
- Cholangiocarcinoma and Gallbladder Cancer Studies
- Eosinophilic Disorders and Syndromes
- Liver physiology and pathology
- Glycosylation and Glycoproteins Research
- COVID-19 Pandemic Impacts
- T-cell and B-cell Immunology
- Cholesterol and Lipid Metabolism
- Neonatal Respiratory Health Research
- COVID-19 Clinical Research Studies
- Medicinal Plant Pharmacodynamics Research
- NF-κB Signaling Pathways
- COVID-19 epidemiological studies
Second Affiliated Hospital of Zhejiang University
2019-2024
Zhejiang Cancer Hospital
2024
Zhejiang University
2020-2024
State Key Laboratory of Respiratory Disease
2020
Abstract Biased signaling of G protein-coupled receptors describes an ability different ligands that preferentially activate alternative downstream pathway. In this work, we identified and characterized N-terminal truncations endogenous chemokine CCL15 as balanced or biased agonists targeting CCR1, presented three cryogenic-electron microscopy structures the CCR1–G i complex in ligand-free form bound to with a resolution 2.6–2.9 Å, illustrating structural basis natural initiates inflammation...
Abstract Chemokine receptors are a family of G-protein-coupled with key roles in leukocyte migration and inflammatory responses. Here, we present cryo-electron microscopy structures two human CC chemokine receptor–G-protein complexes: CCR2 bound to its endogenous ligand CCL2, CCR3 the apo state. The structure CCL2–CCR2–G-protein complex reveals that CCL2 inserts deeply into extracellular half transmembrane domain, forms substantial interactions receptor through most N-terminal glutamine....
MET proto-oncogene (MET) alterations are known driver oncogenes in non-small cell lung cancer (NSCLC).Since the identification of as a potential therapeutic target, extensive clinical trials have been performed.As result, MET-targeted therapies, including tyrosine kinase inhibitors, monoclonal antibodies, and antibodydrug conjugates, now play important roles standard treatment MET-altered NSCLC; they considerably improved outcomes patients with tumors that harbor oncogenic drivers.Although...
Eosinophils primarily secrete CCL6 to promote tumor cell migration and metastasis formation.
Abstract Eosinophils are terminally differentiated cells derived from hematopoietic stem (HSCs) in the bone marrow. Several studies have confirmed effective roles of eosinophils asthmatic airway pathogenesis. However, their regulatory functions not been well elucidated. Here, increased C-C chemokine ligand 6 (CCL6) mice and human orthologs CCL15 CCL23 that highly expressed asthma patients described, which mainly eosinophils. Using Ccl6 knockout mice, further revealed CCL6-dependent allergic...
The nuclear factor κB (NF-κB) pathway plays essential roles in innate and adaptive immunity, but little is known how NF-κB signaling compartmentalized spatiotemporally activated the cytoplasm. Here, we show that lipogenesis signal cascade Scap-SREBP1-S1P/S2P orchestrates homeostasis spatiotemporal activation of NF-κB. SREBP cleavage-activating protein (Scap) sterol regulatory element-binding 1 (SREBP1) form a super complex with inhibitors α (IκBα) to associate close endoplasmic reticulum...
ABSTRACT BACKGROUND The COVID-19 epidemic, first emerged in Wuhan during December 2019, has spread globally. While the mass population movement for Chinese New Year significantly influenced spreading disease, little direct evidence exists about relevance to epidemic and its control of from Wuhan, local emergency response, medical resources China. METHODS Spearman’s correlation analysis was performed between official data confirmed cases Jan 20 th Feb 19 , 2020 real-time travel health data....
Idiopathic pulmonary fibrosis (IPF) is a distressing lung disorder with poor prognosis and high mortality rates. Limited therapeutic options for IPF major clinical challenge. Well-known its anti-apoptotic properties, B-cell lymphoma 2 (Bcl-2) plays critical role in the pathology of malignancies inflammatory diseases, including IPF. In this study, we aimed to investigate effect Bcl-2 homology domain 3 mimetic inhibitor, ABT-199, on bleomycin (BLM)-induced mice, explore possible underlying...
Abstract GPCR-mediated G protein activation cycle contains obligated step of the receptor-G assembly before (pre-coupling state). However, transient nature this pre-coupling state has prevented structural and mechanistic understanding essential cycle. In study, we discover that CCR1 high level state, which allows its rapid response to chemokines. Taking advantage observation, uncover molecular mechanism by solving cryo-electron microscopy structure chemokine receptor in complex with cognate...
Increased levels of cytosolic DNA in lung tissues play an important role acute injury. However, the detailed mechanisms involved remain elusive. Here, we found that cyclic GMP-AMP synthase (cGAS, a sensor) expression was increased airway epithelium response to DNA. Conditional deletion epithelial cGAS exacerbated injury mice, knockdown augmented LPS-induced production interleukin (IL)-6 and IL-8. Mechanically, phosphorylated CREB (cAMP element-binding protein), directly interacted with via...
<b>Background:</b> Chemokine (C-C motif) ligand 6 (CCL6) has recently been identified as a candidate cytokine for asthma; however, the mechanisms by which it contributes to asthma pathogenesis are not well understood. <b>Aims and Objectives:</b> To determine role of CCL6 in airway inflammation murine model allergic asthma. <b>Methods:</b> The expression were examined ovalbumin (OVA) -challenged vivo different types cells under cytokines stimulation vitro. KO mice used investigated effect...
During severe infection-induced acute respiratory distress syndrome, invading microorganisms can cause damage to lung epithelium and promote the release of cytosolic DNA. However, detailed mechanism injury induced by increased DNA from airway remains elusive. To address this question, epithelial cyclic GMP-AMP synthase (cGAS) was deleted in lipopolysaccharide(LPS)-induced mouse model as well human bronchial (HBE) cells. We observed that LPS triggered activate cGAS. Conditional deletion cGAS...
Asthma is a common and chronic respiratory disease. Some asthmatic patients still experience severe symptoms despite appropriate therapies, substantiating need for novel effective treatments. Eosinophils are immune cells derived from hematopoietic stem (HSCs), which critical in airway pathogenesis. However, their regulatory functions have not been well elucidated. Our previous studies indicated that eosinophils disrupted HSC homeostasis by impairing quiescence reconstitution ability. By...
Chemokine receptor CCR1 mediated the eosinophil-committed differentiation, regarded as a potential therapeutic target for asthma treatment. belonged to G protein-coupled receptors (GPCRs). Our previous studies revealed that preferentially activated either protein or β-arrestin-dependent signaling upon different ligands binding, which was called biased signaling. At many GPCRs, events by and β-arrestin were shown have distinct physiological actions from one another. An accurate evaluation of...