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overview Our laboratory is primarily interested in the mechanism of immune regulation by innate immunity in the context of tumors, infections and autoimmune diseases. By understanding how the immune system deals with microbes, tumors and self, we aim to design effective vaccines and therapeutics against cancer and infectious diseases. Presently our study focuses on two classes of proteins: heat shock proteins (HSPs) and Toll-like receptors (TLRs), both of which have been implicated as master regulators of immunity. We and others have discovered that the function of TLRs is dependent on the integrity of the HSP gp96 (or grp94) in the endoplasmic reticulum. Furthermore, depending on its expression level and its subcellular localization, gp96 can initiate systemic autoimmune disease as well as tumor-specific immunity, both of which have a significant clinical relevance. Using a combination of genetic, cell biological, biochemical and immunological tools, we aim to pinpoint the precise mechanism of TLR-gp96 interaction and define the functions of gp96 in hematopoiesis and in the functions of various cellular components in the immune system. In addition, since gp96 is also an important molecule in mediating the unfolded protein response (UPR), works are ongoing to dissect the roles of gp96 in organ development and oncogenesis, and to develop gp96-specific inhibitors for the treatment of diseases with a heavy pathogenic component of inflammation and metabolic dysregulation. Our study has a broad implication in understanding how the immune system operates physiologically and during pathological conditions, in light of the critical roles of TLRs and the UPR in the evolution, function and regulation of the immune response.
phone 843-792-1034
One or more keywords matched the following items that are connected to Li, Zihai
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Academic Article Chaperone gp96-independent inhibition of endotoxin response by chaperone-based peptide inhibitors.
Academic Article Pim1 serine/threonine kinase regulates the number and functions of murine hematopoietic stem cells.
Academic Article a7 helix region of aI domain is crucial for integrin binding to endoplasmic reticulum chaperone gp96: a potential therapeutic target for cancer metastasis.
Academic Article Folding of Toll-like receptors by the HSP90 paralogue gp96 requires a substrate-specific cochaperone.
Academic Article Essential roles of grp94 in gut homeostasis via chaperoning canonical Wnt pathway.
Concept Cytokines
Concept Tandem Mass Spectrometry
Concept DNA, Ribosomal
Concept NK Cell Lectin-Like Receptor Subfamily K
Concept Immunotherapy
Concept Epithelial Cells
Concept Enzyme-Linked Immunosorbent Assay
Concept Protein Binding
Concept Age Factors
Concept Receptors, Antigen, T-Cell, alpha-beta
Concept Neutrophils
Concept T-Lymphocytes, Cytotoxic
Concept Disease Models, Animal
Concept Intestinal Mucosa
Concept Apoptosis
Concept Tumor Burden
Concept Protein Transport
Concept Receptors, Interleukin-1
Concept Anti-Bacterial Agents
Concept Transforming Growth Factor beta
Concept Lung Neoplasms
Concept Protein Folding
Concept RNA, Small Interfering
Concept Basophils
Concept Cyclin D1
Concept Transcription Factor CHOP
Concept Antigens
Concept Caspase 1
Concept Protein Processing, Post-Translational
Concept Receptors, LDL
Concept Heat-Shock Proteins
Concept Interferon-gamma
Concept Animals, Newborn
Concept Interleukin-2 Receptor alpha Subunit
Concept Receptors, Antigen, T-Cell
Concept Immunity, Cellular
Concept Alkylating Agents
Concept Lymphoid Enhancer-Binding Factor 1
Concept Flow Cytometry
Concept Unfolded Protein Response
Concept Tumor Suppressor Protein p53
Concept Prostatic Neoplasms
Concept Neoplasm Metastasis
Concept Inositol 1,4,5-Trisphosphate Receptors
Concept Oncogenes
Concept Proto-Oncogene Proteins c-pim-1
Concept alpha Karyopherins
Concept Staphylococcus
Concept Drug Design
Concept Genes, MHC Class II
Concept Drosophila melanogaster
Concept Pneumococcal Infections
Concept Mice, Inbred BALB C
Concept Fluorescent Antibody Technique
Concept Microscopy, Electron, Transmission
Concept Interleukin-15
Concept Disease Progression
Concept CD8-Positive T-Lymphocytes
Concept Lymphocyte Count
Concept Skin Pigmentation
Concept Immunity
Concept Ubiquitination
Concept Influenza A Virus, H1N1 Subtype
Concept Organogenesis
Concept Immunoglobulin D
Concept PAX5 Transcription Factor
Concept Cell Adhesion Molecules
Concept Medical Oncology
Concept HSP70 Heat-Shock Proteins
Concept Electrophoresis, Gel, Two-Dimensional
Concept Toll-Like Receptors
Concept History, 21st Century
Concept Macrophages
Concept Diethylnitrosamine
Concept HIV-1
Concept Antibodies, Neutralizing
Concept Biomarkers, Tumor
Concept Arginine
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Concept China
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Concept Amino Acid Substitution
Concept Endoplasmic Reticulum
Concept Animals
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Concept Tumor Necrosis Factor Receptor Superfamily, Member 7
Concept Interleukin-23
Concept Disease Susceptibility
Concept Aged
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Concept Dendritic Cells
Concept Ligands
Concept Centrioles
Concept Amino Acid Sequence
Concept Polylysine
Concept Disease-Free Survival
Concept Methylation
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Concept Mice, Knockout
Concept eIF-2 Kinase
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Concept Databases, Genetic
Concept Antineoplastic Agents
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Concept Mesenchymal Stem Cell Transplantation
Concept Neoplasms, Experimental
Concept Carboxymethylcellulose Sodium
Concept Calcium
Concept Hematology
Concept Colorectal Neoplasms
Concept Antibodies, Viral
Concept Blotting, Western
Concept Lymphoma
Concept Histocompatibility Antigens Class I
Concept Pancreatic Neoplasms
Concept T-Lymphocytes, Regulatory
Concept Smad2 Protein
Concept Lipopolysaccharides
Concept Streptococcus pneumoniae
Concept Thrombin
Concept Protein Interaction Domains and Motifs
Concept Anti-Retroviral Agents
Concept Pneumococcal Vaccines
Concept L-Selectin
Concept T-Lymphocyte Subsets
Concept Hyaluronan Receptors
Concept Epitopes, T-Lymphocyte
Concept Germinal Center
Concept Low Density Lipoprotein Receptor-Related Protein-1
Concept Dose-Response Relationship, Drug
Concept Hematopoiesis
Concept Chromatography, Liquid
Concept Head and Neck Neoplasms
Concept Up-Regulation
Concept Lymphocytes, Tumor-Infiltrating
Concept RNA, Bacterial
Concept Immunoprecipitation
Concept Chromatography, Gel
Concept Klebsiella Infections
Concept CD11c Antigen
Concept Mice
Concept Cell Differentiation
Concept Inflammation Mediators
Concept Toll-Like Receptor 9
Concept Bone Marrow Cells
Concept Cysteine
Concept Cyclin-Dependent Kinase 4
Concept Hep G2 Cells
Concept Linear Models
Concept Adenocarcinoma
Concept Microscopy, Confocal
Concept Colitis
Concept Tumor Necrosis Factor-alpha
Concept HIV Infections
Concept Cecum
Concept Immunity, Innate
Concept Matrix Metalloproteinase 9
Concept HSP90 Heat-Shock Proteins
Concept Matrix Metalloproteinase 2
Concept Protein-Arginine N-Methyltransferases
Concept Mice, Inbred C57BL
Concept Klebsiella pneumoniae
Concept Palate
Concept Interleukin-7
Concept Retrospective Studies
Concept GATA1 Transcription Factor
Concept Melanoma, Experimental
Concept Enzyme Activation
Concept Insulin-Secreting Cells
Concept Purines
Concept Influenza A Virus, H3N2 Subtype
Concept RNA, Neoplasm
Concept Pneumonia, Bacterial
Concept Liver Neoplasms
Concept Blood Platelets
Concept Mice, Transgenic
Concept Cell Separation
Concept T-Lymphocytes
Concept Liver Neoplasms, Experimental
Concept Microtubule-Associated Proteins
Concept Transforming Growth Factor beta1
Concept CD11a Antigen
Concept Signal Transduction
Concept Monocytes
Concept Natural Killer T-Cells
Concept Interleukin-2
Concept Immunity, Humoral
Concept Immunoglobulin G
Concept RNA, Messenger
Concept Cell Proliferation
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Concept Protein Multimerization
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Concept Interleukin-1beta
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Concept Lymphocyte Activation
Concept Platelet Aggregation Inhibitors
Concept Periodicals as Topic
Concept Adenine
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Concept Immunotherapy, Adoptive
Concept Insulin-Like Growth Factor II
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Concept Immune Tolerance
Concept Actin Cytoskeleton
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Concept Protein Engineering
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Concept Immunologic Memory
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Concept Genes, MHC Class I
Concept Phosphorylation
Academic Article Molecular chaperone gp96 is a novel therapeutic target of multiple myeloma.
Academic Article Cancer immunotherapy: are we there yet?
Academic Article Immune chaperone gp96 drives the contributions of macrophages to inflammatory colon tumorigenesis.
Academic Article Deletion of CD24 impairs development of heat shock protein gp96-driven autoimmune disease through expansion of myeloid-derived suppressor cells.
Academic Article Plasmacytoid dendritic cells mediate synergistic effects of HIV and lipopolysaccharide on CD27+ IgD- memory B cell apoptosis.
Academic Article Sex differences in monocyte activation in systemic lupus erythematosus (SLE).
Academic Article IL-2Ra mediates temporal regulation of IL-2 signaling and enhances immunotherapy.
Academic Article Interaction of Toll-Like Receptors with the Molecular Chaperone Gp96 Is Essential for Its Activation of Cytotoxic T Lymphocyte Response.
Academic Article Clients and Oncogenic Roles of Molecular Chaperone gp96/grp94.
Academic Article GRP94/gp96 in Cancer: Biology, Structure, Immunology, and Drug Development.
Academic Article Key differences in B cell activation patterns and immune correlates among treated HIV-infected patients versus healthy controls following influenza vaccination.
Academic Article Humoral immune responses to Streptococcus pneumoniae in the setting of HIV-1 infection.
Academic Article GP96: safeguarding Treg.
Academic Article Aberrant high expression of immunoglobulin G in epithelial stem/progenitor-like cells contributes to tumor initiation and metastasis.
Academic Article Nonblocking Monoclonal Antibody Targeting Soluble MIC Revamps Endogenous Innate and Adaptive Antitumor Responses and Eliminates Primary and Metastatic Tumors.
Academic Article Structure-activity relationship in a purine-scaffold compound series with selectivity for the endoplasmic reticulum Hsp90 paralog Grp94.
Academic Article Pass quantity, focus on quality.
Academic Article Centrobin-mediated regulation of the centrosomal protein 4.1-associated protein (CPAP) level limits centriole length during elongation stage.
Academic Article GP96 is a GARP chaperone and controls regulatory T cell functions.
Academic Article Immunobiology and signaling pathways of cancer stem cells: implication for cancer therapy.
Academic Article Endoplasmic reticulum heat shock protein gp96/grp94 is a pro-oncogenic chaperone, not a tumor suppressor.
Academic Article To affinity and beyond: harnessing the T cell receptor for cancer immunotherapy.
Academic Article Cell therapy must be regulated as medicine.
Academic Article Surface Expression of TGF? Docking Receptor GARP Promotes Oncogenesis and Immune Tolerance in Breast Cancer.
Academic Article Targeting inflammasome/IL-1 pathways for cancer immunotherapy.
Academic Article CD24 blunts oral squamous cancer development and dampens the functional expansion of myeloid-derived suppressor cells.
Academic Article Mapping the Interactome of a Major Mammalian Endoplasmic Reticulum Heat Shock Protein 90.
Academic Article Drosophila canopy b is a cochaperone of glycoprotein 93.
Academic Article Murine Th17 cells utilize IL-2 receptor gamma chain cytokines but are resistant to cytokine withdrawal-induced apoptosis.
Academic Article Vaccination with poly(IC:LC) and peptide-pulsed autologous dendritic cells in patients with pancreatic cancer.
Academic Article Gut homeostasis and regulatory T cell induction depend on molecular chaperone gp96 in CD11c+ cells.
Academic Article Platelets subvert T cell immunity against cancer via GARP-TGF? axis.
Academic Article CNPY2 is a key initiator of the PERK-CHOP pathway of the unfolded protein response.
Academic Article Glycoprotein A repetitions predominant (GARP) positively regulates transforming growth factor (TGF) ?3 and is essential for mouse palatogenesis.
Academic Article GRP94 Is an Essential Regulator of Pancreatic ?-Cell Development, Mass, and Function in Male Mice.
Academic Article IL-2 and Beyond in Cancer Immunotherapy.
Academic Article Immunoregulatory functions and the therapeutic implications of GARP-TGF-? in inflammation and cancer.
Academic Article Modulation of Endoplasmic Reticulum Stress Controls CD4+ T-cell Activation and Antitumor Function.
Academic Article Sex Differences in Using Systemic Inflammatory Markers to Prognosticate Patients with Head and Neck Squamous Cell Carcinoma.
Academic Article Recent updates in cancer immunotherapy: a comprehensive review and perspective of the 2018 China Cancer Immunotherapy Workshop in Beijing.
Academic Article GARP Dampens Cancer Immunity by Sustaining Function and Accumulation of Regulatory T Cells in the Colon.
Academic Article Systemic translocation of Staphylococcus drives autoantibody production in HIV disease.
Academic Article Fueling Cancer Immunotherapy With Common Gamma Chain Cytokines.
Academic Article Cutting Edge: Targeting Thrombocytes to Rewire Anticancer Immunity in the Tumor Microenvironment and Potentiate Efficacy of PD-1 Blockade.
Academic Article Moesin, an Ezrin/Radixin/Moesin Family Member, Regulates Hepatic Fibrosis.
Academic Article Thrombin contributes to cancer immune evasion via proteolysis of platelet-bound GARP to activate LTGF-?.
Academic Article Platelet and hemoglobin count at diagnosis are associated with survival in African American and Caucasian patients with colorectal cancer.
Academic Article Rigorous Plasma Microbiome Analysis Method Enables Disease Association Discovery in Clinic.
Academic Article Differential immune signatures in the tumor microenvironment are associated with colon cancer racial disparities.
Academic Article IL6 Fuels Durable Memory for Th17 Cell-Mediated Responses to Tumors.
Concept Proteolysis
Concept Endoplasmic Reticulum Stress
Concept Wnt Signaling Pathway
Concept Th17 Cells
Concept Inflammasomes
Concept Low Density Lipoprotein Receptor-Related Protein-6
Concept CTLA-4 Antigen
Concept Programmed Cell Death 1 Receptor
Concept NLR Proteins
Concept MCF-7 Cells
Concept Molecular Docking Simulation
Concept Carcinogenesis
Concept Beijing
Concept NLR Family, Pyrin Domain-Containing 3 Protein
Concept X-Box Binding Protein 1
Concept Antineoplastic Agents, Immunological
Concept HEK293 Cells
Academic Article Type 2 dendritic cells mediate control of cytotoxic T cell resistant tumors.
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