A5103273662- Immune cells in cancer
- Cardiac Fibrosis and Remodeling
- Cancer, Hypoxia, and Metabolism
- Cancer Cells and Metastasis
- Angiogenesis and VEGF in Cancer
- Mesenchymal stem cell research
- Protease and Inhibitor Mechanisms
- Cancer Immunotherapy and Biomarkers
- Glioma Diagnosis and Treatment
- Single-cell and spatial transcriptomics
- Cancer Research and Treatments
- Blood Coagulation and Thrombosis Mechanisms
- Cellular Mechanics and Interactions
- Connective Tissue Growth Factor Research
- Aortic aneurysm repair treatments
- Cancer-related molecular mechanisms research
- Immunotherapy and Immune Responses
- Phagocytosis and Immune Regulation
- RNA modifications and cancer
- Hematopoietic Stem Cell Transplantation
- Signaling Pathways in Disease
- Lipoproteins and Cardiovascular Health
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Antiplatelet Therapy and Cardiovascular Diseases
- Congenital heart defects research
University of Pennsylvania
2016-2025
Cardiovascular Institute of the South
2022-2024
Guangzhou University of Chinese Medicine
2024
Peking University First Hospital
2020-2023
Peking University
2020-2023
Philadelphia University
2018-2022
China Pharmaceutical University
2017
Cleveland Clinic Lerner College of Medicine
2008-2015
Jacobs (United States)
2008-2014
Cleveland Clinic
2011-2012
Inflammation plays a critical role in the development of cardiovascular diseases. Infiltration leukocytes to sites injury requires their exit from blood and migration across basement membrane; this process has been postulated require remodeling ECM. Plasminogen (Plg) is protease that binds ECM and, upon conversion plasmin, degrades multiple proteins. In addition, plasmin directly activates MMPs. Here, we used Plg(-/-) mice investigate Plg inflammatory leukocyte migration. After induction...
Bone marrow mesenchymal lineage cells are a heterogeneous cell population involved in bone homeostasis and diseases such as osteoporosis. While it is long postulated that they originate from stem cells, the true identity of progenitors their vivo bifurcated differentiation routes into osteoblasts adipocytes remain poorly understood. Here, by employing large scale single transcriptome analysis, we computationally defined at different stages delineated bi-lineage paths young, adult aging mice....
Abstract Spatiotemporal regulation of tumor immunity remains largely unexplored. Here we identify a vascular niche that controls alternative macrophage activation in glioblastoma (GBM). We show tumor-promoting macrophages are spatially proximate to GBM-associated endothelial cells (ECs), permissive for angiocrine-induced polarization. ECs as one the major sources interleukin-6 (IL-6) expression GBM microenvironment. Furthermore, reveal colony-stimulating factor-1 and angiocrine IL-6 induce...
Immunologically-cold tumors including glioblastoma (GBM) are refractory to checkpoint blockade therapy, largely due extensive infiltration of immunosuppressive macrophages (Mϕs). Consistent with a pro-tumor role IL-6 in alternative Mϕs polarization, we here show that targeting by genetic ablation or pharmacological inhibition moderately improves T-cell into GBM and enhances mouse survival; however, does not synergize PD-1 CTLA-4 blockade. Interestingly, anti-IL-6 therapy reduces CD40...
Abstract Angiogenesis is a hallmark of cancer. However, most malignant solid tumors exhibit robust resistance to current anti-angiogenic therapies that primarily target VEGF pathways. Here we report endothelial-mesenchymal transformation induces glioblastoma (GBM) therapy by downregulating VEGFR-2 expression in tumor-associated endothelial cells (ECs). We show markedly reduced human and mouse GBM ECs. Transcriptome analysis verifies ECs under conditions shows increased mesenchymal gene these...
Therapeutic resistance remains a persistent challenge for patients with malignant tumors. Here, we reveal that endothelial cells (ECs) acquire transformation into mesenchymal stem cell (MSC)-like in glioblastoma (GBM), driving tumor to cytotoxic treatment. Transcriptome analysis by RNA sequencing (RNA-seq) revealed ECs undergo and stemness-like activation GBM microenvironment. Furthermore, identified c-Met-mediated axis induces β-catenin phosphorylation at Ser675 Wnt signaling activation,...
Aberrant vascularization is a hallmark of cancer progression and treatment resistance. Here, we have shown that endothelial cell (EC) plasticity drives aberrant chemoresistance in glioblastoma multiforme (GBM). By utilizing human patient specimens, as well allograft genetic murine GBM models, revealed robust allows acquisition fibroblast transformation (also known mesenchymal transition [Endo-MT]), which characterized by EC expression markers, determined prominent population GBM-associated...
: Circulating tumor cells (CTC) are known to be present in the blood of patients with glioblastoma (GBM). Here we report that GBM-derived CTC possess a cancer stem cell (CSC)-like phenotype and contribute local tumorigenesis recurrence by process self-seeding. Genetic probes showed mouse exhibited Sox2/ETn transcriptional activation expressed glioma CSC markers, consistent robust expression stemness-associated genes including SOX2, OCT4, NANOG human GBM patient-derived samples containing...
T cell–based immunotherapy holds promise for treating solid tumors, but its therapeutic efficacy is limited by intratumoral immune suppression. This suppressive tumor microenvironment largely driven tumor-associated myeloid cells, including macrophages. Here, we report that toosendanin (TSN), a small-molecule compound, reprograms macrophages to enforce antitumor immunity in glioblastoma (GBM) mouse models. Our functional screen of genetically probed with chemical library identifies TSN...
Abstract A lipidome comprises thousands of lipid species, many which are isomers and isobars. Liquid chromatography-tandem mass spectrometry (LC-MS/MS), although widely used for lipidomic profiling, faces challenges in differentiating isomers. Herein, we address this issue by leveraging the orthogonal separation capabilities hydrophilic interaction liquid chromatography (HILIC) trapped ion mobility (TIMS). We further integrate isomer-resolved MS/MS methods onto HILIC-TIMS, enable pinpointing...
Cancer immunity is subjected to spatiotemporal regulation by leukocyte interaction with neoplastic and stromal cells, contributing immune evasion immunotherapy resistance. Here, we identify a distinct mesenchymal-like population of endothelial cells (ECs) that form an immunosuppressive vascular niche in glioblastoma (GBM). We reveal spatially restricted, Twist1/SATB1-mediated sequential transcriptional activation mechanism, through which tumor ECs produce osteopontin promote macrophage (Mφ)...
Cancer stem cells (CSCs) - known to be resistant genotoxic radiation and chemotherapy are fundamental therapy failure cancer relapse. Here, we reveal that glioma CSCs hypersensitive radiation, but a temporal DNA repair mechanism converts the intrinsic sensitivity genomic instability treatment resistance. Transcriptome analysis identifies DNA-dependent protein kinase (DNA-PK) as predominant enzyme in CSCs. Notably, DNA-PK activity is suppressed after irradiation when ROS induce dissociation...
Idiopathic pulmonary fibrosis is a progressive fibrotic lung disease, and eventually most patients develop respiratory failure with median survival rate of 2 to 3 years after diagnosis due the lack clinically effective therapies. Mogroside IIIE (MGIIIE), cucurbitane-type compound, was isolated from Siraitia grosvenorii MGIIIE has shown strongest inhibition nitric oxide release, crucial inflammatory factor, lipopolysaccharide (LPS)-treated RAW264.7 cells compared other mogrosides. In mouse...
Granulocyte colony-stimulating factor (G-CSF) is a widespread therapeutic agent for stimulation of hematopoietic progenitor and stem cell (HPSC) mobilization from bone marrow (BM). Plasminogen (Plg) has been shown to be critical HPSC mobilization. Here, we investigated the role Plg in G-CSF-induced underlying mechanism.By using gene-targeted mice, our data show that required egress sinusoidal capillaries BM subsequent peripheral circulation. G-CSF induced Plg-dependent activation matrix...