A5101829470- Ion Transport and Channel Regulation
- Lymphoma Diagnosis and Treatment
- Protein Kinase Regulation and GTPase Signaling
- Metabolism, Diabetes, and Cancer
- Magnesium in Health and Disease
- Immune Cell Function and Interaction
- Melanoma and MAPK Pathways
- Ion Channels and Receptors
- Cancer-related molecular mechanisms research
- CAR-T cell therapy research
- RNA modifications and cancer
- CNS Lymphoma Diagnosis and Treatment
- Calcium signaling and nucleotide metabolism
- Cancer Immunotherapy and Biomarkers
- Histone Deacetylase Inhibitors Research
- Pharmacological Effects of Natural Compounds
- Hearing, Cochlea, Tinnitus, Genetics
- Prostate Cancer Treatment and Research
- Cancer, Lipids, and Metabolism
- Cancer, Hypoxia, and Metabolism
- Medical Research and Treatments
- MicroRNA in disease regulation
- Neuropeptides and Animal Physiology
- Cholesterol and Lipid Metabolism
- Epigenetics and DNA Methylation
Sun Yat-sen University
2020-2025
Sun Yat-sen Memorial Hospital
2021-2025
The University of Texas Southwestern Medical Center
2013-2024
Huazhong University of Science and Technology
2020-2024
Central Hospital of Wuhan
2020-2024
Sun Yat-sen University Cancer Center
2020-2023
State Key Laboratory of Biotherapy
2023
Sichuan University
2018-2023
Southwestern Medical Center
2023
University of Colorado Cancer Center
2022
Structural analysis reveals how chloride inhibits the activation of a kinase implicated in hypertension.
Abstract Background Atherosclerosis has been widely accepted as an inflammatory disease of vascular, adhesion molecules play important role in the early progression it. The aim present study was to evaluate effect kaempferol on such E-selectin (E-sel), intercellular molecule-1 (ICAM-1), vascular cell adhesionmolecule-1 (VCAM-1) and monocyte chemotactic protein-1 (MCP-1) high cholesterol induced atherosclerosis rabbit models. Methods Thirty male New Zealand white (NZW) rabbits were randomly...
The efficacy of CAR-T cells for solid tumors is unsatisfactory. EpCAM a biomarker epithelial tumors, but the clinical feasibility therapy targeting lacking. Here, we report pre- and investigations EpCAM-CAR-T tumors. We demonstrated that costimulated by Dectin-1 exhibited robust antitumor activity without adverse effects in xenograft mouse models EpCAM-humanized mice. Notably, trials (NCT02915445), 6 (50%) 12 enrolled patients experienced self-remitted grade 1/2 toxicities, 1 patient (8.3%)...
Abstract Anti-PD-1 antibodies are a favorable treatment for relapsed or refractory extranodal natural killer T cell lymphoma (RR-ENKTL), however, the complete response (CR) rate and duration of (DOR) need to be improved. This phase 1b/2 study investigated safety efficacy sintilimab, fully human anti-PD-1 antibody, plus chidamide, an oral subtype-selective histone deacetylase inhibitor in 38 patients with RR-ENKTL. Expected objective (ORR) combination was 80%. Patients received escalating...
Purpose: Advanced prostate cancer (PCa) has limited treatment regimens and shows low response to chemotherapy immunotherapy, leading poor prognosis. Histone modification is a vital mechanism of gene expression promising therapy target. In this study, we characterized WD repeat domain 5 (WDR5), regulator histone modification, explored its potential therapeutic value in PCa. Experimental Design: We specific regulators based on TCGA data. The clinical features WDR5 were analyzed two dependent...
Although PD-1/PD-L1 blockade therapy confers salutary effects across cancer types, their efficacy in Extranodal Natural killer/T-cell lymphoma (ENKTCL) patients is limited and unpredictable. Here, we comprehensively evaluated the expression profile of a panel immune-regulatory makers to identify novel prognostic biomarkers and/or therapeutic targets for this malignancy. Using immunohistochemistry multiplex immunofluorescence, found that VISTA (88.1%) was predominantly CD68+ macrophages much...
Abstract Background Bone metastasis is a principal cause of mortality in patients with prostate cancer (PCa). Increasing evidence indicates that high expression stromal interaction molecule 1 (STIM1)-mediated store-operated calcium entry (SOCE) significantly activates the (Ca 2+ ) signaling pathway and involved multiple steps bone PCa. However, regulatory mechanism target therapy STIM1 poorly defined. Methods Liquid chromatography-mass spectrometry analysis was performed to identify...
The accumulation of foam cells in atherosclerotic lesions is a hallmark early-stage atherosclerosis. Kaempferol has been shown to inhibit oxidized low-density lipoprotein (oxLDL) uptake by macrophages; however, the underlying molecular mechanisms are not yet fully investigated. In this study, we that treatment with kaempferol markedly suppresses oxLDL-induced macrophage cell formation, which occurs due decrease lipid and an increase cholesterol efflux from THP-1-derived macrophages....
Background With No Lysine kinase (WNK) signaling regulates mammalian renal epithelial ion transport to maintain electrolyte and BP homeostasis. Our previous studies showed a conserved role for WNK in the regulation of transepithelial Drosophila Malpighian tubule. Methods Using vitro assays transgenic lines, we examined two potential regulators, chloride scaffold protein mouse 25 (Mo25), stimulation flux. Results In , autophosphorylation purified decreased as concentration increased....
Abstract Background Natural killer/T-cell lymphoma (NKTL) is a rare type of aggressive and heterogeneous non-Hodgkin's (NHL) with poor prognosis limited therapeutic options. Therefore, there an urgent need to exploit potential novel targets for the treatment NKTL. Histone deacetylase (HDAC) inhibitor chidamide was recently approved treating relapsed/refractory peripheral T-cell (PTCL) patients. However, its efficacy in NKTL remains unclear. Methods We performed phase II clinical trial...
Abstract Background: Fibroblast growth factor receptor-2b (FGFR2b) is a receptor tyrosine kinase mainly expressed on epithelial cells and involved in numerous cellular functions. Overexpression of FGFR2b solid tumors, especially gastric cancer, associated with poor prognosis, making it compelling candidate for targeting therapy. Methods: ALK201 consists humanized high-affinity FGFR2b-targeting antibody, proprietary, hydrophilic cleavable linker, Exatecan, topoisomerase I inhibitor. Binding...
With no lysine (K) (WNK) kinases regulate epithelial ion transport in the kidney to maintain homeostasis of electrolyte concentrations and blood pressure. Chloride directly binds WNK inhibit autophosphorylation activation. Changes extracellular potassium are thought WNKs through changes intracellular chloride. Prior studies demonstrate that some distal nephron cells, with chronic low- or high-potassium diet. We, therefore, investigated whether regulates activity independent We found...
Background Prostate cancer is a leading cause of cancer-related deaths in men worldwide. Despite advances treatment strategies, there still need for novel therapeutic targets and approaches. Ferroptosis has emerged as critical process the development progression several cancers, including prostate (PCA). In this study, we investigate role MT1G, gene implicated immune responses ferroptosis, pathogenesis PCA. Our objective to elucidate its prognostic significance impact on tumor...
Previous study has demonstrated that the WNK kinases 1 and 3 are direct osmosensors consistent with their established role in cell-volume control. may also be regulated by hydrostatic pressure. Hydrostatic pressure applied to cells culture N2 gas or Drosophila Malpighian tubules centrifugation induces phosphorylation of downstream effectors endogenous WNKs. In vitro, autophosphorylation activity unphosphorylated kinase domain WNK3 (uWNK3) is enhanced a lesser extent than 190 kPa gas....
The MAP kinase cascades, composed of a MAP3K, MAP2K, and MAPK, control switch responses to extracellular stimuli stress in eukaryotes. most important feature these modules is thought be the two double phosphorylation reactions catalyzed by MAP3Ks MAP2Ks. We addressed whether are sequential or random p38 module. Mass spectrometry was used track MAP2K MEK6 MAP3Ks, TAO2 ASK1, subsequent p38α MEK6/S*T* (where S (Ser) T (Thr) sites * denotes phosphorylation). Both precisely ordered....
WNK kinases autoactivate by autophosphorylation. Crystallography of the kinase domain WNK1 phosphorylated on primary activating site (pWNK1) in presence AMP-PNP reveals a well-ordered but inactive configuration. This new pWNK1 structure features specific and unique interactions phosphoserine, less hydration, smaller cavities compared with those unphosphorylated (uWNK1). Because WNKs are activated osmotic stress cells, we addressed whether was influenced directly pressure. crystals formed...
With No Lysine (K) WNK kinases regulate electro-neutral cotransporters that are controlled by osmotic stress and chloride. We showed previously autophosphorylation of WNK1 is inhibited chloride, raising the possibility WNKs activated stress. Here we demonstrate unphosphorylated isoforms 3 1 autophosphorylate in response to pressure vitro, applied with crowding agent polyethylene glycol (PEG)400 or osmolyte ethylene (EG), this activation opposed Small angle x-ray scattering WNK3 presence...
Diffuse large B-cell lymphoma (DLBCL) exhibits frequent inactivating mutations of the histone acetyltransferase CREBBP, highlighting attractiveness targeting CREBBP deficiency as a therapeutic strategy. In this study, we demonstrate that chidamide, novel deacetylase (HDAC) inhibitor, is effective in treating subgroup relapsed/refractory DLBCL patients, achieving an overall response rate (ORR) 25.0% and complete (CR) 15.0%. However, clinical to chidamide remains poor, most patients exhibit...
The MEK1 kinase directly phosphorylates ERK2, after the activation loop of is itself phosphorylated by Raf. Studies over past decade have revealed a large number disease-related mutations in gene that lead to tumorigenesis and abnormal development. Several these result constitutive activity, but how they affect regulation function remains largely unknown. Here, we address questions focusing on two pathogenic variants Phe-53 residue, which maps well-characterized negative regulatory region...
Mildew resistance locus O (Mlo) gene was first found in barley as a powdery mildew susceptibility gene, and recessive mlo alleles confer durable to mildew. To identify candidate Mlo genes rubber tree, HbMlo12 cloned from tree clone CATAS7-33-97, which is susceptible Protein architecture analysis showed that typical protein with seven transmembrane domains. blast search the Arabidopsis thaliana proteome database shared highest similarity AtMlo12, 63% sequence identity. Furthermore, together...