A5013486666- RNA modifications and cancer
- Single-cell and spatial transcriptomics
- Histone Deacetylase Inhibitors Research
- Pancreatic and Hepatic Oncology Research
- Cancer, Hypoxia, and Metabolism
- Cancer Genomics and Diagnostics
- Gene Regulatory Network Analysis
- Protein Degradation and Inhibitors
- Immune cells in cancer
- Bioinformatics and Genomic Networks
- Liver physiology and pathology
- RNA Research and Splicing
- Cholangiocarcinoma and Gallbladder Cancer Studies
- Anesthesia and Neurotoxicity Research
- Microtubule and mitosis dynamics
- Metabolism, Diabetes, and Cancer
- Metal-Catalyzed Oxygenation Mechanisms
- Acute Lymphoblastic Leukemia research
- Colorectal Cancer Treatments and Studies
- Immunotherapy and Immune Responses
- Cell Adhesion Molecules Research
- Advanced Breast Cancer Therapies
- Peptidase Inhibition and Analysis
- PI3K/AKT/mTOR signaling in cancer
- Supramolecular Self-Assembly in Materials
St. Jude Children's Research Hospital
2018-2025
University of Chinese Academy of Sciences
2015-2019
Beijing Institute of Genomics
2015-2019
Chinese Academy of Sciences
2015-2019
BGI Group (China)
2019
Chongqing Medical University
2017
Third Xiangya Hospital
2012
Central South University
2012
Chinese Academy of Medical Sciences & Peking Union Medical College
2001
University of Tennessee at Knoxville
1999
N 6 -methyladenosine (m6A) modification in mRNAs was recently shown to be dynamically regulated, indicating a pivotal role multiple developmental processes. Most recently, it that the Mettl3-Mettl14 writer complex of this mark is required for temporal control cortical neurogenesis. The m6A reader protein Ythdf2 promotes mRNA degradation by recognizing and recruiting decay machinery.We show conditional depletion mice causes lethality at late embryonic stages, with embryos characterized...
Abstract Spatial transcriptomics (ST) has advanced our understanding of tissue regionalization by enabling the visualization gene expression within whole-tissue sections, but current approaches remain plagued challenge achieving single-cell resolution without sacrificing whole-genome coverage. Here we present Spotiphy (spot imager with pseudo-single-cell-resolution histology), a computational toolkit that transforms sequencing-based ST data into single-cell-resolved whole-transcriptome...
Exosomes are 30-120 nm-sized membrane vesicles of endocytic origin that released into the extracellular environment and play roles in cell-cell communication. Tumor-associated macrophages (TAMs) important constituents tumor microenvironment; thus, it is critical to study features complex biological functions TAM-derived exosomes. Here, we constructed a TAM cell model from mouse macrophage line, Ana-1, performed comparative proteomics on exosomes, exosome-free media, cells between TAMs Ana-1....
Mouse model induced by azoxymethane (AOM) and dextran sodium sulfate (DSS) is generally accepted as an ideal object to study on the carcinogenesis mechanisms of human colorectal cancer (CRC). The genomic responses AOM/DSS treatment in mouse that possibly lead elucidation CRC pathological mechanism are still poorly understood. For first time, we investigated genome landscape exome sequencing, testify its molecular faithfulness CRC. Of 14 neoplastic samples, 7575 somatic variants were...
Many signaling and other genes known as "hidden" drivers may not be genetically or epigenetically altered differentially expressed at the mRNA protein levels, but, rather, drive a phenotype such tumorigenesis via post-translational modification mechanisms. However, conventional approaches based on genomics differential expression are limited in exposing hidden drivers. Here, we present comprehensive algorithm toolkit NetBID2 (data-driven network-based Bayesian inference of drivers, version...
Abstract Benzophenones are widely supplemented in personal care products, but little is known about its neurodevelopmental toxicity. The previous epidemiological study discovered a negative correlation between maternal exposure to benzophenone metabolite 4‐hydroxybenzophenone (4HBP) and child's neurodevelopment, yet the causal relationship detailed mechanism remain be defined. Here, it reported that prenatal, not postnatal, environmentally relevant level of 4HBP impairs hippocampus...
Background: The PI3K/Akt/mTOR pathway in part impacts tumorigenesis through modulation of host immune activity. To assess the effects Akt inhibition on tumor micro-environment (TME), we analyzed tissue from patients with operable hormone receptor positive, HER2 negative breast cancer (BC) treated a presurgical trial inhibitor MK-2206. Methods: Quantitative multiplex immunofluorescence (qmIF) was performed using CD3, CD8, CD4, FOXP3, CD68, and pancytokeratin biopsy surgical specimens MK-2206...
A priority in solving the problem of drug resistance is to understand molecular mechanism how a induces response within cells. Because many cancer cells exhibit chromosome aneuploidy, we explored whether changes aneuploidy status result resistance. Two typical colorectal cells, HCT116 and LoVo, were cultured with chemotherapeutic drugs irinotecan (SN38) or oxaliplatin (QxPt), non- drug-resistant cell lines selected. Whole exome sequencing (WES) was employed evaluate these RNAseq LC-MS/MS...
Hepatoblastoma (HB) is the most common pediatric liver cancer. Its predominant occurrence in very young children led us to investigate whether neonatal provides a protumorigenic niche HB development.HB development was compared between orthotopic transplantation models established postnatal day 5 (P5) and 60 (P60) mice (P5Tx P60Tx models). Single-cell RNA-sequencing (sc-RNAseq) performed using tumor tissues from both top candidate cell types genes identified are investigated for their roles...
The sparse nature of single-cell omics data makes it challenging to dissect the wiring and rewiring transcriptional signaling drivers that regulate cellular states. Many drivers, referred as "hidden drivers", are difficult identify via conventional expression analysis due low inconsistency between RNA protein activity caused by post-translational other modifications. To address this issue, we developed scMINER, a mutual information (MI)-based computational framework for unsupervised...
Prognosis of children with high-risk hepatoblastoma (HB), the most common pediatric liver cancer, remains poor. In this study, we found ribonucleotide reductase (RNR) subunit M2 (RRM2) was one key genes supporting cell proliferation in HB. While standard chemotherapies could effectively suppress RRM2 HB cells, they induced a significant upregulation other RNR subunit, RRM2B. Computational analysis revealed distinct signaling networks and RRM2B were involved patient tumors, participating...
Somatic mitochondrial DNA (mtDNA) mutations are prevalent in tumors, yet defining their biological significance remains challenging due to the intricate interplay between selective pressure, heteroplasmy, and cell state. Utilizing bulk whole-genome sequencing data from matched tumor normal samples two cohorts of pediatric cancer patients, we uncover differences accumulation synonymous nonsynonymous mtDNA leukemias, indicating distinct pressures. By integrating single-cell (SCS) with...
Transforming growth factor β (TGF-β) family ligands are key regulators of dendritic cell (DC) differentiation and activation. Epidermal Langerhans cells (LCs) require TGF-β signaling for their differentiation, canonical TGF-β1 secures a non-activated LC state. LCs reportedly control skin inflammation replenished from peripheral blood monocytes, which also give rise to pro-inflammatory monocyte-derived DCs (moDCs). By studying mechanisms in inflammation, we previously screened versus moDCs...
Database searches of MS/MS spectra are the main approach to peptide/protein identification in proteomics. Since most database search engines only utilize a small portion original signals for peptide detection, how improve quality is primary concern enhancement rate. A fundamental issue that some noise MS signals, informative or uninformative, have be filtered out prior searching. Herein, an integrative preprocessing algorithm was designed, termed pClean, which incorporates three modules...
Abstract Intrahepatic cholangiocarcinoma (iCCA) is characterized by its highly desmoplastic stroma. Myofibroblasts (MFs) are present both within the tumor mass (intratumoral MFs, iMFs) and at border (peritumoral pMFs). Using a spheroid-based coculture system, we show that initial iCCA-pMF contact growth suppressive to cells. However, prolonged interaction elicits significant cell invasion dissemination. We find vascular adhesion molecule-1 ( Vcam1 ) level elevated in cells with pMFs but low...
ABSTRACT Despite the anticancer activity of pan-histone deacetylase (HDAC) inhibitors, their clinical use has been limited due to toxicity. However, development more specific inhibitors that selectively inhibit individual HDACs is emerging as a novel and well-tolerated alternative. Here, we present results first trial evaluating ricolinostat (the leading HDAC6 inhibitor) in breast cancer (BC) patients. We have developed computational network-based algorithm evaluate protein, based on...
Despite the anticancer activity of pan-histone deacetylase (HDAC) inhibitors, their clinical use has been limited due to toxicity. However, development more specific inhibitors that selectively inhibit individual HDACs is emerging as a novel and well-tolerated alternative. Here, we present results first trial evaluating ricolinostat (the leading HDAC6 inhibitor) in breast cancer (BC) patients.We have developed computational network-based algorithm evaluate protein, based on enrichment its...
CYP3A5 is a cytochrome P450 (CYP) enzyme that metabolizes drugs and contributes to drug resistance in cancer. However, it remains unclear whether directly influences cancer progression. In this report, we demonstrate regulates glucose metabolism pancreatic ductal adenocarcinoma. Multi-omics analysis showed knockdown results decrease various glucose-related metabolites through its effect on transport. A mechanistic study revealed enriches the transporter GLUT1 at plasma membrane by...