A5058775810- CAR-T cell therapy research
- Virus-based gene therapy research
- Mesenchymal stem cell research
- Immune Cell Function and Interaction
- Biosimilars and Bioanalytical Methods
- T-cell and B-cell Immunology
- RNA Interference and Gene Delivery
- Monoclonal and Polyclonal Antibodies Research
- Immune cells in cancer
- Nanowire Synthesis and Applications
- Extracellular vesicles in disease
- Advancements in Semiconductor Devices and Circuit Design
- Cancer Cells and Metastasis
- Viral Infectious Diseases and Gene Expression in Insects
- Adipokines, Inflammation, and Metabolic Diseases
- Genetics, Bioinformatics, and Biomedical Research
- CRISPR and Genetic Engineering
- Electrostatic Discharge in Electronics
- Sarcoma Diagnosis and Treatment
- Protein Tyrosine Phosphatases
- Bone and Dental Protein Studies
- Statistical and Computational Modeling
- MicroRNA in disease regulation
- Pesticide and Herbicide Environmental Studies
- Pesticide Exposure and Toxicity
UNC Lineberger Comprehensive Cancer Center
2020-2024
University of North Carolina at Chapel Hill
2020-2024
University of Chinese Academy of Sciences
2021-2023
Shanghai Institute of Nutrition and Health
2020-2023
Shanghai Institutes for Biological Sciences
2012-2020
Shanghai Jiao Tong University
2010-2016
Chinese Academy of Sciences
2012-2016
Institute of Endocrinology
2014
Ruijin Hospital
2014
University of Science and Technology Beijing
2007
Mesenchymal stem cells (MSCs) have been employed successfully to treat various immune disorders in animal models and clinical settings. Our previous studies shown that MSCs can become highly immunosuppressive upon stimulation by inflammatory cytokines, an effect exerted through the concerted action of chemokines nitric oxide (NO). Here, we show also enhance responses. This immune-promoting occurred when proinflammatory cytokines were inadequate elicit sufficient NO production. When inducible...
An imbalance between normal adipogenesis and osteogenesis by mesenchymal stem cells (MSCs) has been shown to be related various human metabolic diseases, such as obesity osteoporosis; however, the underlying mechanisms remain elusive. We found that interaction osteopontin (OPN), an arginine-glycine-aspartate-containing glycoprotein, integrin αv/β1 plays a critical role in lineage determination of MSCs. Although OPN is well-established marker during osteogenesis, its MSC differentiation still...
Multiple sclerosis (MS) is a chronic and debilitating autoimmune disease, characterized by inflammatory demyelination in the nervous tissue subsequent neurological dysfunction. Spermidine, natural polyamine, has been shown to affect inflammation some experimental models. We show here that spermidine could alleviate encephalomyelitis (EAE), model for MS, through regulating infiltration of CD4+ T cells macrophages central system. Unexpectedly, we found treatment MOG-specific did not their...
Abstract Obesity-associated chronic inflammation is characterized by an accumulation of adipose tissue macrophages (ATMs). It generally believed that those are derived from peripheral blood monocytes. However, recent studies suggest local proliferation responsible for ATM accumulation. In the present study, we revealed both migration and contribute to during obesity development. We show there a significant increase in ATMs at early stage obesity, which largely due enhanced situ macrophage...
CAR T therapy targeting solid tumors is restrained by limited infiltration and persistence of those cells in the tumor microenvironment (TME). Here, we developed approaches to enhance activity using an orthotopic model locally advanced breast cancer. generated from Th/Tc17 given with STING agonists DMXAA or cGAMP greatly enhanced control, which was associated cell TME. Using single-cell RNA sequencing, demonstrate that promoted trafficking persistence, supported generation a chemokine milieu...
Obesity-associated inflammation is accompanied by the accumulation of adipose tissue macrophages (ATMs), which believed to predispose obese individuals insulin resistance. CD11b (integrin αM) highly expressed on monocytes and critical for their migration function. We found here that high-fat diet-induced resistance was significantly reduced in CD11b-deficient mice. Interestingly, recruitment impaired when deficient, although cellularity ATMs mice higher than wild-type further increase caused...
Abstract Purpose: The development of safe and effective chimeric antigen receptor (CAR) T-cell therapy for acute myeloid leukemia (AML) has largely been limited by the concomitant expression most AML-associated surface antigens on normal progenitors potential prolonged disruption hematopoiesis immunotargeting these antigens. purpose this study was to evaluate B7-homolog 3 (B7-H3) as a target AML-directed CAR therapy. B7-H3, coreceptor belonging B7 family immune checkpoint molecules, is...
MSCs possess potent immunosuppressive capacity. We have reported that mouse inhibit T cell proliferation and function via nitric oxide. This immune regulatory capacity of is induced by the inflammatory cytokines IFNγ together with either TNFα or IL-1β. effect on extraordinary; logarithmic increases in expression iNOS chemokines are often observed. To investigate molecular mechanisms underlying this robust cytokines, we examined microRNAs before after cytokine treatment. found miR-155 most...
Abstract Chimeric antigen receptor (CAR) tonic signaling, defined as spontaneous activation and release of proinflammatory cytokines by CAR-T cells, is considered a negative attribute because it leads to impaired antitumor effects. Here, we report that CAR signaling caused the intrinsic instability mAb single-chain variable fragment (scFv) promote self-aggregation via CD3ζ chain incorporated into construct. This phenomenon was detected in encoding either CD28 or 4-1BB costimulatory...
Abstract p53 plays a pivotal role in controlling the differentiation of mesenchymal stem cells (MSCs) by regulating genes involved cell cycle and early steps process. In context osteogenic MSCs bone homeostasis, osteoprotegerin/receptor activator NF-κB ligand/receptor (OPG/RANKL/RANK) axis is critical signaling pathway. The absence or loss function has been implicated aberrant that results higher formation versus erosion, leading to an unbalanced remodeling. Here, we show microCT mice with...
Recent reports have highlighted the roles of free fatty acid receptor 2 (FFAR2) in regulation metabolic and inflammatory processes. However, potential function FFAR2 type 1 diabetes (T1D) remains unexplored. Our results indicated that mRNA level was upregulated peripheral blood mononuclear cells T1D patients. The human promoter regions were cloned, luciferase reporter assays revealed NFκB activation induced expression. Furthermore, we showed by overexpression cell apoptosis through ERK...
Mesenchymal stromal cells (MSCs) are strongly immunosuppressive via producing nitric oxide (NO) and known to migrate into tumor sites promote growth, but the underlying mechanisms remain largely elusive. Here, we found that interferon alpha (IFNα)-secreting MSCs showed more dramatic inhibition effect on progression than of IFNα alone. Interestingly, IFNα-primed could also effectively suppress growth. Mechanistically, demonstrated both IFNβ (type I IFNs) reversed splenocyte proliferation....
Abstract CD28 and 4-1BB costimulatory endodomains included in chimeric antigen receptor (CAR) molecules play a critical role promoting sustained antitumor activity of CAR-T cells. However, the molecular events associated with ectopic constitutive display either or cells have been only partially explored. In current study, we demonstrated that incorporated within CAR leads to cell cluster formation death forms both apoptosis necroptosis absence tonic signaling. Mechanistic studies illustrate...
Osteoblasts and adipocytes are derived from a common precursor, mesenchymal stem cells (MSCs). Alterations in the normal fate of differentiating MSCs involved development obesity osteoporosis. Here, we report that viable motheaten (me(v)) mice, which deficient SH2-domain-containing phosphatase-1 (SHP1), develop osteoporosis spontaneously. Consistently, me(v)/me(v) mice exhibit significantly reduced osteogenic potential greatly increased adipogenic potential. When were transplanted into nude...
CD19-redirected chimeric antigen receptor (CAR.CD19) T cells promote clinical responses in patients with relapsed/refractory B-cell non-Hodgkin lymphomas and chronic lymphocytic leukemia (CLL). However, showing sustained after CAR.CD19-T treatment show increased infection risk due to compromised B-lymphocyte recovery. Mature B cell-derived malignancies express monoclonal immunoglobulins bearing either κ- or λ-light chains. We initially constructed CAR-T targeting the κ-light-chain (CAR.κ)...