- Immunotherapy and Immune Responses
- Growth Hormone and Insulin-like Growth Factors
- Extracellular vesicles in disease
- Diabetes and associated disorders
- vaccines and immunoinformatics approaches
- Diabetes Management and Research
- Pancreatic function and diabetes
- Ubiquitin and proteasome pathways
- Cancer-related Molecular Pathways
- RNA modifications and cancer
- Monoclonal and Polyclonal Antibodies Research
- Estrogen and related hormone effects
- CAR-T cell therapy research
- RNA Research and Splicing
- Advanced Proteomics Techniques and Applications
- Peptidase Inhibition and Analysis
- Bone Metabolism and Diseases
- Glycosylation and Glycoproteins Research
- Vitamin D Research Studies
- Diabetes Treatment and Management
- MicroRNA in disease regulation
- T-cell and B-cell Immunology
- Endoplasmic Reticulum Stress and Disease
- Colorectal and Anal Carcinomas
- Cancer Immunotherapy and Biomarkers
National Taiwan University Hospital
2025
A*STAR Graduate Academy
2025
Southern Medical University
2023-2025
Nanfang Hospital
2023-2025
Tongji Hospital
2012-2024
Huazhong University of Science and Technology
2012-2024
Singapore Immunology Network
2022-2024
National University of Singapore
2005-2024
Utrecht University
2016-2024
Wuhan No.1 Hospital
2023-2024
Clinical and experimental evidence has shown that tumor-associated macrophages promote cancer initiation progression. However, the macrophage-derived molecular determinants regulate colorectal metastasis have not been fully characterized. Here, we demonstrate M2 macrophage-regulated cells' migration invasion is dependent upon exosomes (MDE). MDE displayed a high expression level of miR-21-5p miR-155-5p, MDE-mediated depended on these two miRNAs. Mechanistically, miR-155-5p were transferred...
Extracellular vesicles (EVs) are a potential source of disease-associated biomarkers for diagnosis. In breast cancer, comprehensive analyses EVs could yield robust and reliable subtype-specific that still critically needed to improve diagnostic routines clinical outcome. Here, we show proteome profiles secreted by different cancer cell lines highly indicative their respective molecular subtypes, even more so than the changes within cells. Moreover, detected evidence biological processes...
Pediatric patients with high-risk neuroblastoma have poor survival rates and urgently need more effective treatment options less side effects. Since novel improved immunotherapies may fill this need, we dissect the immunoregulatory interactions in by single-cell RNA-sequencing of 24 tumors (10 pre- 14 post-chemotherapy, including 5 pairs) to identify strategies for optimizing immunotherapy efficacy. Neuroblastomas are infiltrated natural killer (NK), T B cells, immunosuppressive myeloid...
Abstract Cardiac progenitor cell (CPC)‐derived small extracellular vesicles (sEVs) exhibit great potential to stimulate cardiac repair. However, the multifaceted nature of sEV heterogeneity presents a challenge in understanding distinct mechanisms underlying their regenerative abilities. Here, dual‐step multimodal flowthrough and size‐exclusion chromatography method was applied isolate separate CPC‐derived subpopulations study functional differences related repair responses. Three were...
Significance Nearly all proteins are posttranslationally modified, a phenomenon known to alter protein function. Recently, multiple posttranslational modifications (PTMs) have been documented exist on the same proteins, revealing an additional level of complexity (named “PTM crosstalk”) that, due its dynamic nature, is challenging predict. Here, we propose motif for PTM crosstalk between two most common PTMs: phosphorylation and O-GlcNAcylation. Through use kinetic-based high-resolution mass...
The proteasome inhibitor bortezomib (BTZ) is successfully applied in the treatment of multiple myeloma, but its efficacy restricted by wide-spread occurrence resistance. Metabolic alterations play an important role cancer development and aid cellular adaptation to pharmacologically changed environments. changes could therefore essential drug However, specific metabolic pathways that can be targeted improve therapy remain unidentified.We elucidated mechanisms underlying resistance using mass...
Because of the low stoichiometry protein phosphorylation, targeted enrichment prior to LC–MS/MS analysis is still essential. The trend in phosphoproteome shifting toward an increasing number biological replicates per experiment, ideally starting from very sample amounts, placing new demands on protocols make them less labor-intensive, more sensitive, and prone variability. Here we assessed automated protocol using Fe(III)-IMAC cartridges AssayMAP Bravo platform meet these demands....
HER2/ERBB2-overexpressing breast cancers targeted effectively by the small-molecule kinase inhibitor lapatinib frequently acquire resistance to this drug. In study, we employed explorative mass spectrometry profile proteome, kinome, and phosphoproteome changes in an established model of systematically investigate initial response subsequent reprogramming resistance. The resulting dataset, which collectively contains quantitative data for >7,800 proteins, >300 protein kinases, >15,000...
Abstract SGLT2 (sodium-glucose cotransporter 2) is an important mediator of epithelial glucose transport and has been reported that SGLT2, robustly diffusely expressed in malignant cancer cells, was overexpressed various tumors, inhibiting the expression significantly inhibited tumor progression. By blocking functional activity inhibitors have shown anticancer effects several cancers, including breast cancer, cervical hepatocellular prostate lung cancer. However, effect osteosarcoma specific...
The dysregulated expression of immune checkpoint molecules enables cancer cells to evade destruction. While blockade inhibitory checkpoints like PD-L1 forms the basis current immunotherapies, a deficiency in costimulatory signals can render these therapies futile. CD58, ligand, plays crucial role antitumor responses, but mechanisms controlling its remain unclear. Using two systematic approaches, we reveal that CMTM6 positively regulates CD58 expression. Notably, interacts with both and...
Abstract Osteoclasts consume an amount of adenosine triphosphate (ATP) to perform their bone resorption function in the development osteoporosis. However, mechanism underlying osteoclast energy metabolism has not been fully elucidated. In addition glucose, glutamine (Glu) is another major carrier produce ATP. role Glu osteoclasts and related molecular mechanisms poorly Here we show that required for differentiation function, deprivation or pharmacological inhibition transporter ASCT2 by...
Glycosylated mucin proteins contribute to the essential barrier function of intestinal epithelium. The transmembrane MUC13 is an abundant glycoprotein with important functions for mucosal maintenance that are not yet completely understood. We demonstrate in human epithelial monolayers, localized both apical surface and tight junction (TJ) region on lateral membrane. deletion resulted increased transepithelial resistance (TEER) reduced translocation small solutes. TEER buildup ΔMUC13 cells...
Background and Aims A novel bioactive peptide, mitochondrial-derived peptide (MOTS-c), has recently attracted attention as a potential prevention or therapeutic option for obesity type 2 diabetes mellitus (T2DM). MOTS-c profiles have not yet been reported in human T2DM. We aimed to determine circulating levels explore the association between various metabolic parameters. Methods In this case-control study, 40 obese children adolescents (27 males) 57 controls (40 were recruited Hubei Province...
Tumor heterogeneity is a major cause of therapeutic resistance. Immunotherapy may exploit alternative vulnerabilities drug-resistant cells, where tumor-specific human leukocyte antigen (HLA) peptide ligands are promising leads to invoke targeted anti-tumor responses. Here, we investigate the variability in HLA class I presentation between different clonal cells same colorectal cancer patient, using an organoid system. While clone-specific differences were observed, broad inter-clone was even...
Osteosarcoma (OS) is a malignant solid tumor prone to lung metastasis that occurs in adolescents aged 15-19 years. Neoadjuvant chemotherapy and surgical treatment aimed at curing OS have gained limited progress over the last 30 Exploring new effective second-line therapies for patients serious challenge researchers. Quercetin, multiple biologically active polyphenolic flavonoid, has been used therapy. However, exact mechanism of quercetin still unknown, which limits application quercetin. In...
Abstract Extracellular vesicles (EVs) are cell-derived lipid bilayer-enclosed particles that play a role in intercellular communication. Cardiac progenitor cell (CPC)-derived EVs have been shown to protect the myocardium against ischemia-reperfusion injury via pro-angiogenic effects. However, mechanisms underlying CPC-EV-induced angiogenesis remain elusive. Here, we discovered ability of CPC-EVs induce vitro and stimulate pro-survival pathways was lost upon EV donor exposure calcium...
A major scientific drive is to characterize the protein-coding genome as it provides primary basis for study of human health. But fundamental question remains: what has been missed in prior genomic analyses? Over past decade, translation non-canonical open reading frames (ncORFs) observed across cell types and disease states, with implications proteomics, genomics, clinical science. However, impact ncORFs limited by absence a large-scale understanding their contribution proteome. Here, we...
ABSTRACT ATP-citrate lyase (ACLY), generating most of the nucleocytosolic acetyl coenzyme A (acetyl-CoA) for histone acetylation, links cell metabolism to epigenetic regulation. Recent investigations demonstrated that ACLY activated by metabolic reprogramming played an essential role in both M1 and M2 macrophage activation via acetylation. Previous studies also revealed methylation acetylation were critical transcriptional regulation osteoclast-specific genes. Considering osteoclast...
FBXW7 is an E3 ubiquitin ligase that targets proteins for proteasome-mediated degradation and mutated in various cancer types. Here, we use CRISPR base editors to introduce different hotspot mutations human colon organoids. Functionally, mutation reduces EGF dependency of organoid growth by ~10,000-fold. Combined transcriptomic proteomic analyses revealed increased EGFR protein stability mutants. Two distinct phosphodegron motifs reside the cytoplasmic tail EGFR. Mutations these occur...
Chronic bacterial infection increased the risk of many solid malignancies and underlying mechanism is usually ascribed to bacterial-caused inflammation. However, direct interaction infectious bacteria with cancer cells has been largely overlooked. We identified that highly metastatic breast MDA-MB-231 expressed high level Toll-like receptor 2 (TLR2) in contrast poorly homogenous untransformed cells. TLR2 were actively triggered by peptidoglycan (PGN) from bacterium Staphylococcus aureus...
Metastasis accounts largely for the high mortality rate of colorectal cancer (CRC) patients. In this study, we performed comparative proteome analysis primary CRC cell lines HCT-116 and its metastatic derivative E1 using 2-D DIGE. We identified 74 differentially expressed proteins, many which function in transcription, translation, angiogenesis signal transduction, or cytoskeletal remodeling pathways, are indispensable cellular processes involved cascade. Among these stathmin-1 (STMN1) was...