- Adenosine and Purinergic Signaling
- Bioinformatics and Genomic Networks
- Cancer Immunotherapy and Biomarkers
- Genetic Associations and Epidemiology
- Single-cell and spatial transcriptomics
- Pancreatic and Hepatic Oncology Research
- Adolescent and Pediatric Healthcare
- Cancer Cells and Metastasis
- Fungal and yeast genetics research
- Gene expression and cancer classification
- Epigenetics and DNA Methylation
- Cancer Genomics and Diagnostics
- Alzheimer's disease research and treatments
- Lung Cancer Research Studies
- Peptidase Inhibition and Analysis
- Tryptophan and brain disorders
- RNA modifications and cancer
- interferon and immune responses
- Ferroptosis and cancer prognosis
- Cancer-related molecular mechanisms research
- RNA Research and Splicing
- Genetics, Bioinformatics, and Biomedical Research
- Peroxisome Proliferator-Activated Receptors
- Genomics and Rare Diseases
- Phagocytosis and Immune Regulation
The University of Texas Health Science Center at Houston
2017-2024
Traditional Chinese Medicine Hospital of Kunshan
2023
Shanghai University of Traditional Chinese Medicine
2023
Changchun University of Chinese Medicine
2022
Shanghai Institutes for Biological Sciences
2013-2018
Chinese Academy of Sciences
2013-2018
Vanderbilt University
2017
Center for Excellence in Molecular Cell Science
2016
Shanghai Entry-Exit Inspection and Quarantine Bureau
2000
Abstract Human complex traits and common diseases show tissue- cell-type- specificity. Recently, single-cell RNA sequencing (scRNA-seq) technology has successfully depicted cellular heterogeneity in human tissue, providing an unprecedented opportunity to understand the context-specific expression of trait-associated genes tissue-cell types (TCs). Here, we present first web-based application quickly assess cell-type-specificity genes, named Web-based Cell-type Specific Enrichment Analysis...
Existing functional description of genes are categorical, discrete, and mostly through manual process. In this work, we explore the idea gene embedding, distributed representation genes, in spirit word embedding.From a pure data-driven fashion, trained 200-dimension vector all human using co-expression patterns 984 data sets from GEO databases. These vectors capture relatedness terms recovering known pathways - average inner product (similarity) within pathway is 1.52X greater than that...
Abstract Drug response differs substantially in cancer patients due to inter- and intra-tumor heterogeneity. Particularly, transcriptome context, especially tumor microenvironment, has been shown playing a significant role shaping the actual treatment outcome. In this study, we develop deep variational autoencoder (VAE) model compress thousands of genes into latent vectors low-dimensional space. We then demonstrate that these encoded could accurately impute drug response, outperform standard...
Diseases and traits are under dynamic tissue-specific regulation. However, heterogeneous tissues often collected in biomedical studies, which reduce the power identification of disease-associated variants gene expression profiles.We present deTS, an R package, to conduct enrichment analysis with two built-in reference panels. Statistical methods developed implemented for detecting genes test different forms query data. Our applications using multi-trait genome-wide association studies data...
The coronavirus disease 2019 (COVID-19) is an infectious that mainly affects the host respiratory system with ~ 80% asymptomatic or mild cases and 5% severe cases. Recent genome-wide association studies (GWAS) have identified several genetic loci associated COVID-19 symptoms. Delineating variants genes important for better understanding its biological mechanisms. We implemented integrative approaches, including transcriptome-wide (TWAS), colocalization analysis, functional element prediction...
Abstract The microenvironment that surrounds pancreatic ductal adenocarcinoma (PDAC) is profoundly desmoplastic and immunosuppressive. Understanding triggers of immunosuppression during the process tumorigenesis would aid in establishing targets for effective prevention therapy. Here, we interrogated differential molecular mechanisms dependent on cell origin subtype promote PDAC initiation established tumors. Transcriptomic analysis cell-of-origin–dependent epithelial gene signatures...
Exhaustion of T cells limits their ability to clear chronic infections or eradicate tumors. Here, in the context transplant, we investigated whether cell exhaustion occurs and has a role determining transplant outcome. A peptide/MHC tetramer-based approach was used track exhausted CD8+ male-to-female skin model. Transplant large whole-tail skins, but not small tail skins (0.8 cm × 0.8 cm), led anti-male tetramer+ subsequently acceptance grafts. To study CD4+ exhaustion, TCR-transgenic B6 TEa...
Abstract Background Opioid use disorder (OUD) affects millions of people, causing nearly 50 000 deaths annually in the United States. While opioid exposure and OUD are known to cause widespread transcriptomic epigenetic changes, few studies human samples have been conducted. Understanding how brain at molecular level could help decipher disease pathogenesis shed light on treatment. Methods We generated genome-wide DNA methylation profiles 22 subjects 19 non-psychiatric controls. applied...
Abstract Background The rapid accumulation of single-cell RNA sequencing (scRNA-seq) data presents unique opportunities to decode the genetically mediated cell-type specificity in complex diseases. Here, we develop a new method, scGWAS, which effectively leverages scRNA-seq achieve two goals: (1) infer cell types disease-associated genes manifest and (2) construct cellular modules imply disease-specific activation different processes. Results scGWAS only utilizes average gene expression for...
<p>The effects of Pdgfrb+ CAF vs ASC-like depletion on the TME. A, tumor section immunofluorescence for CD3 (Red) expression to measure T-cell infiltration and nuclei (blue) (left), CD3+ cell quantification (right). B, endomucin (green) quantify endothelial density In A-B, each tumor, a minimum 15 fields (10X) were taken quantified using Image J. Images converted 8-bit threshold was applied only highlight percent area measured. An average calculated all images per tumor. Scale...
<p>The effects of <i>Pdgfrb</i>+ CAF vs. ASC-like depletion on the TME. Shown are representative analyses tumors from <a href="#fig1" target="_blank">Figs. 1</a> and href="#fig2" target="_blank">2</a>. <b>A,</b> t-distributed stochastic neighbor embedding clusters with cell populations identified based heatmap analysis (not shown) show changes in labeled populations. <b>B,</b> Changes frequencies cells corresponding to...
<div>Abstract<p>Immune checkpoint blockade therapy, transformative in some cancer types, has remained ineffective for patients with pancreatic cancer. The effects of subpopulations cancer-associated fibroblasts (CAF) on progression and therapy resistance are incompletely understood. In this study, the roles CAFs expressing platelet-derived growth factor receptor β (<i>Pdgfrb</i>) markers adipose stromal cells (ASC) were analyzed mice ductal adenocarcinoma. Ablation...
<p>A, Fig. 1 schematic of testing the effect Pdgfrb+ CAF depletion on PDAC progression. B, initial body weight in experiment A. C, A tumor section H&E staining showing inflammation (i), necrosis (n), and well-differentiated cells (arrows). D, Pdgfrb + pre-depletion E, D. F, weights G, 2 ASC-like H, G. I, G indicating (n) Scale Bars = 500μm. *=p<0.05.</p>
<p>ASC-like CAF depletion synergizes with immune checkpoint blockade. Following orthotopic grafting of KPC-Luc cells, female (<i>N</i> = 3 per group) and male mice received PBS, D-CAN, aPDL1, or the combination D-CAN + aPDL1. <b>A,</b> IVIS images two representative at day 22 showing location pancreatic primary tumor graft (arrow) extrapancreatic area invasion metastases (punctate). <b>B,</b> KPC size upon resection from females males....
<p>The effect of ASC-like CAF depletion on orthotopic PDAC progression. Tissues resected from male mice after 25 days D-CAN (<i>N</i> = 3) or control PBS treatment were analyzed. <b>A,</b> KPC tumor size upon resection. <b>B,</b> Representative tumors. <b>C,</b> Paraffin sections tumors in <b>B</b> stained with hematoxylin/eosin, trichrome blue, subjected to αSMA and endomucin immunofluorescence. Arrows indicate examples...
<p>The effect of <i>Pdgfrb</i>+ CAF depletion on orthotopic PDAC progression. Tissues resected from <i>Pdgfrb-TK</i> male mice after 25 days GCV (<i>N</i> = 3) or control PBS 4) treatment were analyzed. <b>A,</b> KPC tumor size upon resection. <b>B,</b> Representative tumors. <b>C,</b> Paraffin sections tumors in <b>B</b> stained with hematoxylin/eosin, trichrome blue, subjected to αSMA and endomucin...
<p>A, Fig. 4 schematic testing if D-CAN synergizes with immune checkpoint blockade (aPDL1) in male and female mice. B, Initial body weights experimental C, Tumor weight from an experiment mice investigating the effects of / aPDL1 non-immune IgG + data combined 4B 4D data. *=p<0.05, **=p<0.001, ***=p<0.0001. D, Metastatic liver tumor colony assay C.</p>
The gene Polymorphic derived intron-containing, known as Pldi, is a long non-coding RNA (lncRNA) first discovered in mouse. Although parts of its sequence were reported to be conserved rat and human, it can only expressed mouse testis with mouse-specific transcription start site. consensus Pldi also part an antisense transcript AK158810 wide range tissues.
Abstract Aggressiveness of carcinomas is linked with tumor recruitment adipose stromal cells (ASC), which increased in obesity. ASC promote cancer through molecular pathways not fully understood. Here, we demonstrate that epithelial–mesenchymal transition (EMT) prostate tumors promoted by obesity and suppressed upon pharmacological depletion HiMyc mice, a spontaneous genetic model cancer. CXCL12 expression was associated localized to expressing platelet-derived growth factor receptors Pdgfra...