- Cellular transport and secretion
- Lipid Membrane Structure and Behavior
- Pancreatic function and diabetes
- Signaling Pathways in Disease
- Endoplasmic Reticulum Stress and Disease
- Angiogenesis and VEGF in Cancer
- Cell Adhesion Molecules Research
- Cellular Mechanics and Interactions
- Proteoglycans and glycosaminoglycans research
- Cancer, Hypoxia, and Metabolism
- Peptidase Inhibition and Analysis
- Biochemical and Structural Characterization
- Mesenchymal stem cell research
- Fibroblast Growth Factor Research
- Medical Imaging and Pathology Studies
- Microtubule and mitosis dynamics
- Muscle Physiology and Disorders
- Calcium signaling and nucleotide metabolism
- Connective tissue disorders research
- Nitric Oxide and Endothelin Effects
- Chemokine receptors and signaling
- Cancer Research and Treatment
- Skin and Cellular Biology Research
- Molecular Junctions and Nanostructures
- Photosynthetic Processes and Mechanisms
China-US (Henan) Hormel Cancer Institute
2024
Harvard University
2011-2023
Brigham and Women's Hospital
2011-2023
Institute of Biophysics
2018
Chinese Academy of Sciences
2018
Huashan Hospital
2017
Fudan University
2017
Beijing Geriatric Hospital
2016
Beijing Hospital
2016
University of Bristol
2012
Vascular endothelial growth factor (VEGF) is a potent and specific mitogen for vascular cells promotes neovascularization in vivo. To determine whether interleukin-1 beta (IL-1 beta), which present atherosclerotic lesions, induces VEGF gene expression smooth muscle cells, we performed RNA blot analysis on rat aortic (RASMC) with cDNA probe. IL-1 increased mRNA levels RASMC time- dose-dependent manner. As little as 0.1 ng/ml by 2-fold 10 4-fold. We also measured the half-life of nuclear...
In comparison to the internalization pathways of endocytosis, recycling are less understood. Even defined is process regulated recycling, as few examples exist and their underlying mechanisms remain be clarified. this study, we examine endocytic integrin β1, a that has been suggested play an important role during cell motility by mediating redistribution integrins migrating front. External stimulation regulates itinerary mainly at internal compartment likely subset endosomes. This...
Whether coat proteins play a widespread role in endocytic recycling remains unclear. We find that ACAP1, GTPase-activating protein (GAP) for ADP-ribosylation factor (ARF) 6, is part of novel clathrin complex regulated by ARF6 two key physiological settings, stimulation-dependent integrin critical cell migration and insulin-stimulated glucose transporter type 4 (Glut4), which required homeostasis. These findings not only advance basic understanding an early mechanistic step but also shed...
At ribbon synapses, where exocytosis is regulated by graded depolarization, vesicles can fuse very rapidly with the plasma membrane (complete discharge of releasable pool in approximately 200 msec). Vesicles are also retrieved (time constant 1 sec), leading us to wonder whether their retrieval uses an unusual mechanism. To study this, we exposed isolated bipolar neurons from goldfish retina cationized ferritin. This electron-dense marker uniformly decorated cell and was carried into during...
Abstract Heparan sulfates in the extracellular matrix are required for a variety of biological processes, including cellular response to heparin-binding growth factors. However, little is known regarding regulation their expression and composition under pathophysiological conditions. In present study, we have investigated two key heparan sulfate chain–carrying core proteins, syndecan-1 syndecan-4, mouse/rat infarct model tissue injury repair. Induction myocardial infarction was associated...
There has been considerable controversy regarding the lineage relationship between smooth muscle cells (SMCs) and myofibroblasts, because they express a number of common cell-selective markers including (SM) alpha-actin. We have shown previously that MCAT elements within SM alpha-actin promoter confer differential activity in cultured SMCs versus myofibroblasts. In present study, to determine role vivo, we generated transgenic mice harboring an promoter-enhancer-LacZ reporter gene containing...
Binding of basic fibroblast growth factor (FGF2) to its high affinity receptors requires the presence specific heparan sulfate (HS) moieties on cell surface that act as coreceptors. To determine contribution cell-surface HS modulation FGF2-dependent growth, we studied changes in mass and FGF2 binding endothelial under normoxic hypoxic conditions vitro. Both large vein cardiac microvascular cells cultured demonstrated an increase ratio chondroitin (CS), well number low (HS-associated) sites...
Background— Discrepancy exists between the potent effects of therapeutic angiogenesis in laboratory animals and marginal results observed patients with advanced coronary artery disease. In vitro small animal data suggest that may depend on locally available nitric oxide (NO), but impact endothelial dysfunction myocardium has been unclear. We compared clinically applicable methods swine which was experimentally induced to normal swine. Methods Results— Miniswine were fed either a regular...
Endosomal transport represents the primary mode for intracellular trafficking and signaling transduction thus has to be tightly controlled. The molecular processes controlling endosomal positioning utilize several large protein complexes, one of which contains small GTPase Rab7, Rab-interacting lysosomal (RILP), oxysterol-binding protein–related 1 (ORP1L). Rab7 is known interact with RILP through a canonical binding site termed effector-interacting switch region, but it not clear how...
Oncomodulin (Ocm) is a myeloid cell–derived growth factor that enables axon regeneration in mice and rats after optic nerve injury or peripheral injury, yet the mechanisms underlying its activity are unknown. Using proximity biotinylation, coimmunoprecipitation, surface plasmon resonance, ectopic expression, we have identified armadillo-repeat protein C10 (ArmC10) as high-affinity receptor for Ocm. ArmC10 deletion suppressed inflammation-induced injured nerves of mice. also ability lesioned...
Vascular endothelial growth factor (VEGF) is an angiogenic known to be up-regulated in ischemic heart and hypoxic cells. However, the transcriptional regulation of VEGF hypoxia-induced angiogenesis not fully understood. Transcriptional enhancer factor-1 (TEF-1) a family that can regulate many genes expressed cardiac skeletal muscle cells by binding myocyte-specific chloramphenicol acetyltransferase heptamer elements promoters these genes. In this study, we demonstrated related TEF-1...
Significance Coat proteins play a central role in the intracellular transport pathways by coupling two main functions: bending membrane to generate carriers and binding cargoes for their sorting into these carriers. Studies thus far have mostly solved structure of coat solution, but functional form requires assembly on protein complexes. Here, we pursued cryo-EM reveal molecular detail how SNX1 assembles deform membrane. When compared previously retromer-SNX complex, our elucidation also...
Chronic obstructive pulmonary disease (COPD) is a common, complex and major cause of morbidity mortality. Although multiple genetic determinants COPD have been implicated by genome-wide association studies (GWASs), the pathophysiological significance these associations remains largely unknown. From protein-protein interaction network module, we selected path between two GWAS genes for validation studies: FAM13A (family with sequence similarity 13 member A)-AP3D1-CTGF- TGFβ2. We find that...
Foam cells play a key role in the occurrence and pathogenesis of atherosclerosis. Its formation starts with ingestion oxidized low-density lipoprotein (oxLDL). The process is associated Ras related protein brain 5 (Rab5) which plays critical regulating endocytosis early endosomal trafficking. Base on this, we presumed that Rab5 might participate maturation foam cell. aim this study to investigate effect macrophage cholesterol during evolvement when induced by oxLDL Immunohistochemistry was...
SUMMARY The ADP-Ribosylation Factor (ARF) small GTPases have been found to act in vesicle fission through a direct ability tubulate membrane. Here, we used cryo-electron microscopy (EM) solve the structure of an ARF6 protein lattice assembled on tubulated membrane 3.9 Å resolution. forms tetramers that polymerize into helical arrays form this lattice. We identify, and confirm functionally, contacts critical for formation. solved also suggests how ARF amphipathic helix is positioned...
Studies on the Bin-Amphiphysin-Rvs (BAR) domain have advanced a fundamental understanding of how proteins deform membrane. We previously showed that BAR in tandem with Pleckstrin Homology (PH domain) underlies assembly ACAP1 (Arfgap Coil-coil, Ankryin repeat, and PH I) into an unusual lattice structure also uncovers new paradigm for protein deforms Here, we initially pursued computation-based refinement to identify its critical contacts. Simulation studies then revealed ACAP1, which...