A5053690577- Genomics and Chromatin Dynamics
- Parkinson's Disease Mechanisms and Treatments
- Gene expression and cancer classification
- RNA Research and Splicing
- RNA and protein synthesis mechanisms
- Bioinformatics and Genomic Networks
- Cancer-related molecular mechanisms research
- Genetic Associations and Epidemiology
- Alzheimer's disease research and treatments
- Single-cell and spatial transcriptomics
- Epigenetics and DNA Methylation
- Nuclear Receptors and Signaling
- RNA modifications and cancer
- Chromosomal and Genetic Variations
- Circular RNAs in diseases
- Molecular Biology Techniques and Applications
- CRISPR and Genetic Engineering
- Genetics, Aging, and Longevity in Model Organisms
- Genomics and Phylogenetic Studies
- Genetic Neurodegenerative Diseases
- Genetic Mapping and Diversity in Plants and Animals
- Extracellular vesicles in disease
- Cancer Genomics and Diagnostics
- MicroRNA in disease regulation
- Genomic variations and chromosomal abnormalities
Yale University
2024-2025
Brigham and Women's Hospital
2015-2024
Harvard University
2015-2024
Research Network (United States)
2021-2024
University of Massachusetts Chan Medical School
2011-2020
National Institute of Standards and Technology
2020
University of Bergen
2008-2014
Uni Research (Norway)
2014
Friedrich Miescher Institute
2014
Southeast University
2007
Chromatin immunoprecipitation coupled with high-throughput sequencing (ChIP-seq) has become the dominant technique for mapping transcription factor (TF) binding regions genome-wide. We performed an integrative analysis centered around 457 ChIP-seq data sets on 119 human TFs generated by ENCODE Consortium. identified highly enriched sequence motifs in most sets, revealing new and validating known ones. The motif sites (TF sites) are conserved evolutionarily show distinct footprints upon DNase...
Copy number mutations implicate excess production of α-synuclein as a possibly causative factor in Parkinson's disease (PD). Using an unbiased screen targeting endogenous gene expression, we discovered that the β2-adrenoreceptor (β2AR) is regulator (SNCA). β2AR ligands modulate SNCA transcription through histone 3 lysine 27 acetylation its promoter and enhancers. Over 11 years follow-up 4 million Norwegians, agonist salbutamol, brain-penetrant asthma medication, was associated with reduced...
The Encyclopedia of DNA Elements (ENCODE) consortium aims to identify all functional elements in the human genome including transcripts, transcriptional regulatory regions, along with their chromatin states and methylation patterns. ENCODE project generates data utilizing a variety techniques that can enrich for such as immunoprecipitation (ChIP), micrococcal nuclease (MNase) digestion DNase I digestion, followed by deeply sequencing resulting DNA. As part project, we have developed...
Previous work has demonstrated that chromatin feature levels correlate with gene expression. The ENCODE project enables us to further explore this relationship using an unprecedented volume of data. Expression from more than 100,000 promoters were measured a variety high-throughput techniques applied RNA extracted by different protocols cellular compartments several human cell lines. also generated the genome-wide mapping eleven histone marks, one variant, and DNase I hypersensitivity sites...
Alpha-synuclein (αS) is a conformationally plastic protein that reversibly binds to cellular membranes. It aggregates and genetically linked Parkinson's disease (PD). Here, we show αS directly modulates processing bodies (P-bodies), membraneless organelles function in mRNA turnover storage. The N terminus of αS, but not other synucleins, dictates mutually exclusive binding either membranes or P-bodies the cytosol. associates with multiple decapping proteins close proximity on Edc4 scaffold....
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...
Abstract Glaucoma, a leading cause of irreversible blindness, is highly heritable human disease. Previous genome-wide association studies have identified over 100 loci for the most common form, primary open-angle glaucoma. Two key glaucoma-associated traits also show high heritability: intraocular pressure and optic nerve head excavation damage quantified as vertical cup-to-disc ratio. Here, since much glaucoma heritability remains unexplained, we conducted large-scale multitrait study in...
Statistical models have been used to quantify the relationship between gene expression and transcription factor (TF) binding signals. Here we apply large-scale data generated by ENCODE project study transcriptional regulation TFs. Our results reveal a notable difference in prediction accuracy of levels start sites (TSSs) captured different technologies RNA extraction protocols. In general, TSSs with high CpG content are more predictable than those low content. For genes alternative TSSs,...
Transcriptional dysregulation has long been recognized as central to the pathogenesis of Huntington's disease (HD). MicroRNAs (miRNAs) represent a major system post-transcriptional regulation, by either preventing translational initiation or targeting transcripts for storage degradation. Using next-generation miRNA sequencing in prefrontal cortex (Brodmann Area 9) twelve HD and nine controls, we identified five miRNAs (miR-10b-5p, miR-196a-5p, miR-196b-5p, miR-615-3p miR-1247-5p)...
Abstract Background Whole‐genome sequencing data are available from several large studies across a variety of diseases and traits. However, massive storage computation resources required to use these data, achieve sufficient power for discoveries, harmonization multiple cohorts is critical. Objectives The Accelerating Medicines Partnership Parkinson's Disease program has developed research platform disease (PD) that integrates the analysis whole‐genome RNA expression clinical harmonized...
The genetic origins of nanoscale extracellular vesicles in our body fluids remains unclear. Here, we perform a tracking analysis urinary exosomes via RNA sequencing, revealing that urine mostly express tissue-specific genes for the bladder and have close cell-genetic relationships to endothelial cell, basal monocyte, dendritic cell. Tracking differentially expressed cancers corresponding enrichment show are intensively involved immune activities, indicating they may be harnessed as reliable...
Little is known about circular RNAs (circRNAs) in specific brain cells and human neuropsychiatric disease. Here, we systematically identify over 11,039 circRNAs expressed vulnerable dopamine pyramidal neurons laser-captured from 190 brains non-neuronal using ultra-deep, total RNA sequencing. 1526 3308 are custom-tailored to the cell identity of enriched synapse pathways. 29% Parkinson's 12% Alzheimer's disease-associated genes produced validated circRNAs. circDNAJC6, which transcribed a...
Genomic regulatory blocks (GRBs) are chromosomal regions spanned by highly conserved non-coding elements (HCNEs), most of which serve as inputs one target gene in the region. The genes often transcription factors involved embryonic development and differentiation. GRBs contain extensive deserts, well additional 'bystander' intertwined with HCNEs but whose expression function unrelated to those gene. tight regulation genes, complex arrangement inputs, differential responsiveness region call...
There are no cures for neurodegenerative diseases and this is partially due to the difficulty of monitoring pathogenic molecules in patients during life. The Parkinson's disease gene α-synuclein (SNCA) selectively expressed blood cells neurons. Here we show that SNCA transcripts circulating paradoxically reduced early stage, untreated dopamine transporter neuroimaging-supported three independent regional, national, international populations representing 500 cases 363 controls on analogue...
To investigate epigenetic contributions to Huntington's disease (HD) pathogenesis, we carried out genome-wide mapping of the transcriptional mark, trimethyl-histone H3-lysine 4 (H3K4me3) in neuronal nuclei extracted from prefrontal cortex HD cases and controls using chromatin immunoprecipitation followed by deep-sequencing. Neuron-specific distribution H3K4me3 revealed 136 differentially enriched loci associated with genes implicated development neurodegeneration, including GPR3, TMEM106B,...
Hox cluster organization represents a valuable marker to study the effects of recent genome duplication in salmonid fish (25–100 Mya). Using polymerase chain reaction amplification cDNAs, BAC library screening, and walking, we reconstructed 13 clusters Atlantic salmon containing 118 genes including 8 pseudogenes. paralogs resulting from preceding radiation ray-finned have been much better preserved than other model teleosts. The last lineage has followed by loss 1 4 HoxA clusters. Four...