A5100775657- Cellular Mechanics and Interactions
- Cell Adhesion Molecules Research
- T-cell and B-cell Immunology
- Immune Cell Function and Interaction
- Immunotherapy and Immune Responses
- CAR-T cell therapy research
- Liver Diseases and Immunity
- Liver Disease Diagnosis and Treatment
- Silicon Carbide Semiconductor Technologies
- Systemic Lupus Erythematosus Research
- Eosinophilic Esophagitis
- Tuberculosis Research and Epidemiology
- Toxoplasma gondii Research Studies
- Phagocytosis and Immune Regulation
- Protein Tyrosine Phosphatases
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- IL-33, ST2, and ILC Pathways
- Protein Kinase Regulation and GTPase Signaling
- Parasitic Infections and Diagnostics
- Ion channel regulation and function
- Rheumatoid Arthritis Research and Therapies
- Herpesvirus Infections and Treatments
- Immune Response and Inflammation
- 3D Printing in Biomedical Research
- Cellular transport and secretion
Zhejiang Lab
2022-2025
University of Pittsburgh
2021-2025
Lunenfeld-Tanenbaum Research Institute
2002-2024
University of Toronto
2009-2024
Mount Sinai Hospital
2004-2024
Toronto General Hospital Research Institute
2003-2024
Toronto General Hospital
2002-2024
Jinzhou Medical University
2019-2024
Guangdong Pharmaceutical University
2024
China Three Gorges University
2024
Over the past two decades, immunotherapies have increasingly been considered as first-line treatments for most cancers. One such treatment is immune checkpoint blockade (ICB), which has demonstrated promising results against various solid tumors in clinical trials. Monoclonal antibodies (mAbs) are currently available inhibitors (ICIs). These ICIs target specific checkpoints, including cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) and programmed cell death protein 1 (PD-1). Clinical...
The Wiskott-Aldrich syndrome protein (WASp) has been implicated in modulation of lymphocyte activation and cytoskeletal reorganization. To address the mechanisms whereby WASp subserves such functions, we have examined roles development using mice carrying a WAS null allele (WAS−/−). Enumeration hemopoietic cells these animals revealed total numbers thymocytes, peripheral B T lymphocytes, platelets to be significantly diminished relative wild-type mice. In thymus, this abnormality was...
WAVE2 is a member of the Wiskott-Aldrich syndrome protein family cytoskeletal regulatory proteins shown to link Rac activation actin remodeling via induction Arp 2/3 activity. thought be regulated by its positioning in macromolecular complex also containing Abelson-(Abl) interactor-1 (Abi-1) adaptor, but molecular basis and biologic relevance inclusion this are ill defined. Here we show that Abi-1 binding mediated discrete motifs coiled-coil WAVE-homology domains increases markedly...
Involvement of the Wiskott-Aldrich syndrome protein (WASp) in promoting cell activation requires its release from autoinhibitory structural constraints and has been attributed to WASp association with activated cdc42. Here, however, we show that T development receptor (TCR)-induced proliferation actin polymerization proceed normally WASp−/− mice expressing a transgene lacking cdc42 binding domain. By contrast, mutation tyrosine residue Y291, identified here as major site TCR-induced...
Objective To identify risk alleles relevant to the causal and biologic mechanisms of antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis (AAV). Methods A genome‐wide association study subsequent replication were conducted in a total cohort 1,986 cases AAV (patients with granulomatosis polyangiitis [Wegener's] [GPA] or microscopic [MPA]) 4,723 healthy controls. Meta‐analysis these data sets functional annotation identified loci performed, candidate disease variants unknown...
Abstract Ocular injuries and their complications represent the most common causes of visual impairment. For ocular surgery, there is an unmet need for highly transparent bioadhesives with superior adhesion, biocompatibility, regenerative properties. Herein, a novel high‐transparent bioadhesive hydrogel composed gelatin methacryloyl (GelMA) dopamine methacrylamide (DMA) developed by in situ oxidative free‐radical polymerization. This overcomes fundamental weakness mussel‐inspired adhesive...
Abstract Although CD19-specific chimeric antigen receptor (CAR) T cells are curative for patients with relapsed or refractory large B-cell lymphoma (R/R LBCL), disease relapse tumor antigen-positive remains a challenge. Cytokine/chemokine-expressing CAR-T could overcome suppressive milieu, but the clinical safety and efficacy of this therapy remain unclear. Here we report preclinical development capable expressing interleukin (IL)-7 chemokine (C-C motif) ligand (CCL)-19 upon CD19 engagement...
Glioblastoma-derived exosomes (GDEs), containing nucleic acids, proteins, fatty acids and other substances, perform multiple important functions in glioblastoma microenvironment. Tumor-derived serve as carriers of induce a shift metabolism towards oxidative phosphorylation, thus driving immune dysfunction dendritic cells (DCs). Lipid peroxidation is an characteristic ferroptosis. Nevertheless, it remains unclear whether GDEs can lipid accumulation oxidation to trigger ferroptosis DCs. In our...
Induction of T cell antigen receptor (TCR) endocytosis has a significant impact on TCR signaling and behavior, but the molecular interactions coordinating internalization activated are poorly understood. Previously we have shown that is regulated by Wiskott Aldrich Syndrome protein (WASp), cytosolic effector which, upon interaction with cdc42 Rho GTPase, couples engagement to Arp 2/3 complex-mediated actin polymerization. Here report WASp associates in cells intersectin 2, an endocytic...
Activated T cells rapidly assemble filamentous (F-) actin networks in response to ligation of the cell receptor or upon interaction with adhesive stimuli order facilitate migration and formation immune synapse. Branched filament assembly is crucial for this process dependent activation Arp2/3 complex by nucleation-promoting factor Wiskott-Aldrich Syndrome protein (WASp). Genetic disruption WAS gene has been linked hematopoietic malignancies various cytopenias. Although contributions WASp...
DC apoptosis has been observed in patients with cancer and sepsis, defects have implicated the development of autoimmune diseases. However, mechanisms how affects immune responses, are unclear. In this study, we showed that immature viable ability to uptake apoptotic as well necrotic without it being recognized an inflammatory event by DC. specific converted into tolerogenic DC, which were resistant LPS-induced maturation. These secreted increased levels TGF-beta1, induced differentiation...
A forward genetic screen of mice treated with the mutagen ENU identified a mutant mouse chronic motor incoordination. This mutant, named Pingu (Pgu), carries missense mutation, an I402T substitution in S6 segment voltage-gated potassium channel Kcna2. The gene Kcna2 encodes α-subunit Kv1.2, which is abundantly expressed large axon terminals basket cells that make powerful axo-somatic synapses onto Purkinje cells. Patch clamp recordings from cerebellar slices revealed increased frequency and...
The Wiskott-Aldrich syndrome protein (WASp) plays a major role in coupling T cell antigen receptor (TCR) stimulation to induction of actin cytoskeletal changes required for activation. Here, we report that WASp inducibly binds the sorting nexin 9 (SNX9) cells and WASp, SNX9, p85, CD28 colocalize within clathrin-containing endocytic vesicles after TCR/CD28 costimulation. implicated clathrin-mediated endocytosis, via its SH3 domain uses PX interact with phosphoinositol 3-kinase regulatory...
Neutrophil chemotaxis depends on actin dynamics, but the roles for specific cytoskeleton regulators in this response remain unclear. By analysis of mammalian diaphanous-related formin 1 (mDia1)-deficient mice, we have identified an essential role nucleator neutrophil chemotaxis. Lack mDia1 was associated with defects chemoattractant-induced polymerization, polarization, and directional migration, also impaired activation RhoA, its downstream target p160-Rho-associated coil-containing protein...
Schwann cells elaborate myelin sheaths around axons by spirally wrapping and compacting their plasma membranes. Although actin remodeling plays a crucial role in this process, the effectors that modulate cell cytoskeleton are poorly defined. Here, we show cytoskeletal regulator, neural Wiskott-Aldrich syndrome protein (N-WASp), is upregulated myelinating coincident with elaboration. When N-WASp conditionally deleted at onset of myelination, continue to ensheath but fail extend processes...
Cytoskeletal regulatory protein dysfunction has been etiologically linked to inherited diseases associated with immunodeficiency and autoimmunity, but the mechanisms involved are incompletely understood. Here, we show that conditional Wave2 ablation in T cells causes severe autoimmunity increased mammalian target of rapamycin (mTOR) activation metabolic reprogramming engender spontaneous accelerated differentiation peripheral cells. These mice also manifest diminished antigen-specific cell...