A5057792439- Cancer-related molecular mechanisms research
- RNA modifications and cancer
- Mycobacterium research and diagnosis
- Cancer-related gene regulation
- Microbial Natural Products and Biosynthesis
- Genomics and Phylogenetic Studies
- T-cell and B-cell Immunology
- RNA and protein synthesis mechanisms
- Immune Cell Function and Interaction
- Genetic Associations and Epidemiology
- interferon and immune responses
- Plant and Fungal Species Descriptions
- Genomics and Chromatin Dynamics
- Transplantation: Methods and Outcomes
- Adipose Tissue and Metabolism
- Epigenetics and DNA Methylation
- RNA Research and Splicing
- Single-cell and spatial transcriptomics
- SARS-CoV-2 and COVID-19 Research
- Immune responses and vaccinations
- Bioinformatics and Genomic Networks
- Synthesis and Catalytic Reactions
- Plant Diversity and Evolution
- Lymphoma Diagnosis and Treatment
- CRISPR and Genetic Engineering
Children's Hospital of Philadelphia
2018-2025
Shaanxi Normal University
2016-2025
Myongji University
2020-2025
Center for Excellence in Molecular Cell Science
2024
Chinese Academy of Sciences
2024
New York University
2024
Amgen (United States)
2024
Xishuangbanna Tropical Botanical Garden
2023
Northwest A&F University
2018-2022
Smithsonian Institution
2019-2020
Abstract Osteoporosis is a devastating disease with an essential genetic component. GWAS have discovered signals robustly associated bone mineral density (BMD), but not the precise localization of effector genes. Here, we carry out physical and direct variant to gene mapping in human mesenchymal progenitor cell-derived osteoblasts employing massively parallel, high resolution Capture C based method order simultaneously characterize genome-wide interactions all promoters. By intersecting our...
Horizontal gene transfer (HGT) is the of genetic material across species boundaries and has been a driving force in prokaryotic evolution. HGT involving eukaryotes appears to be much less frequent, functional implications are poorly understood. We test hypothesis that parasitic plants, because their intimate feeding contacts with host plant tissues, especially prone horizontal acquisition. sought evidence HGTs transcriptomes three members Orobanchaceae, family containing spanning full...
Abstract Systemic lupus erythematosus (SLE) is mediated by autoreactive antibodies that damage multiple tissues. Genome-wide association studies (GWAS) link >60 loci with SLE risk, but the causal variants and effector genes are largely unknown. We generated high-resolution spatial maps of variant accessibility gene connectivity in human follicular helper T cells (TFH), a cell type required for anti-nuclear characteristic SLE. Of ~400 potential regulatory identified, 90% exhibit proximity...
One of the most robust synthetic lethal interactions observed in multiple functional genomic screens has been dependency on PRMT5 cancer cells with MTAP deletion. We report discovery clinical stage MTA-cooperative inhibitor AMG 193, which preferentially binds presence MTA and potent biochemical cellular activity MTAP-deleted across lineages. In vitro, inhibition induces DNA damage, cell cycle arrest, aberrant alternative mRNA splicing cells. human line patient-derived xenograft models, 193...
Gram-negative bacteria of the genus Serratia are potential producers many useful secondary metabolites, such as prodigiosin and serrawettins, which have applications in environmental bioremediation or pharmaceutical industry. Several strains produce serrawettin W1 main bioactive compounds, biosynthetic pathways co-regulated by quorum sensing (QS). In contrast, strain, can simultaneously W2, has not been reported. This study focused on analyzing genomic sequence sp. strain YD25T isolated from...
The pioneer transcription factor (TF) PU.1 controls hematopoietic cell fate by decompacting stem heterochromatin and allowing nonpioneer TFs to enter otherwise inaccessible genomic sites. deficiency fatally arrests lymphopoiesis myelopoiesis in mice, but human congenital disorders have not previously been described. We studied six unrelated agammaglobulinemic patients, each harboring a heterozygous mutation (four de novo, two unphased) of SPI1, the gene encoding PU.1. Affected patients...
To uncover novel significant association signals (p<5×10 −8 ), genome-wide studies (GWAS) requires increasingly larger sample sizes to overcome statistical correction for multiple testing. As an alternative, we aimed identify associations among suggestive (5 × 10 ≤p<5×10 −4 ) in powered GWAS efforts using chromatin accessibility and direct contact with gene promoters as biological constraints. We conducted retrospective analyses of three GIANT BMI ATAC-seq promoter-focused Capture C...
Abstract Background SARS-CoV-2 infection results in a broad spectrum of COVID-19 disease, from mild or no symptoms to hospitalization and death. disease severity has been associated with some pre-existing conditions the magnitude adaptive immune response SARS-CoV-2, recent genome-wide association study (GWAS) risk critical illness revealed significant genetic component. To gain insight into how human variation attenuates exacerbates following infection, we implicated putatively functional...
Cowpea (Vigna unguiculata) cultivar B301 is resistant to races SG4 and SG3 of the root parasitic weed Striga gesnerioides, developing a hypersensitive response (HR) at site parasite attachment. By contrast, race SG4z overcomes resistance successfully parasitises plant. Comparative transcriptomics in silico analysis identified small secreted effector protein dubbed Suppressor Host Resistance 4z (SHR4z) haustorium that upon transfer host roots causes loss immunity (i.e. decreased HR increased...
Neurodevelopmental disorders are thought to arise from interrupted development of the brain at an early age. Genome-wide association studies (GWAS) have identified hundreds loci associated with susceptibility neurodevelopmental disorders; however, which noncoding variants regulate genes these is often unclear. To implicate neuronal GWAS effector genes, we performed integrated analysis transcriptomics, epigenomics and chromatin conformation changes during Induced pluripotent stem cell-derived...
Abstract The hypothalamus regulates metabolic homeostasis by influencing behavior and endocrine systems. Given its role governing key traits, such as body weight reproductive timing, understanding the genetic regulation of hypothalamic development function could yield insights into disease pathogenesis. However, given inaccessibility, studying human gene has proven challenging. To address this gap, we generate a high-resolution chromatin architecture atlas an established embryonic stem cell...
Genes act in concert with each other specific contexts to perform their functions. Determining how these genes influence complex traits requires a mechanistic understanding of expression regulation across different conditions. It has been shown that this insight is critical for developing new therapies. Transcriptome-wide association studies have helped uncover the role individual disease-relevant mechanisms. However, modern models architecture predict gene-gene interactions play crucial...
<p>Supplementary Methods: SDMA Imaging Assay, ELISA, Immunohistochemistry</p>
<p>Supplementary Figure S6. AM-9747 treatment results in increased DNA damage and cellular senescence BxPC-3 cells</p>
<p>Supplementary Figure S8. AMG 193 treatment in BxPC-3 tumors does not affect circulating blood cells</p>
<p>Supplementary Figure S5. <i>In vitro</i> target validation, RNA-seq, and additional cell cycle data in WT MTAP-deleted tumor cells</p>
<p>Supplementary Figure S2. SPR AMG 193 competitive chaser experiment</p>
<p>Supplementary Figure S3. HCT116 isogenic pair validation</p>
<p>Supplementary Figure S1. SPR chaser characterization</p>
<p>Supplementary Figure S7. Time course SDMA analysis, CDX models versus AMG 193, and AM-9747 PDX trial</p>