A5009760322- Genomics and Chromatin Dynamics
- Epigenetics and DNA Methylation
- RNA modifications and cancer
- RNA Research and Splicing
- DNA Repair Mechanisms
- Single-cell and spatial transcriptomics
- Cancer Genomics and Diagnostics
- RNA and protein synthesis mechanisms
- Bioinformatics and Genomic Networks
- Gene expression and cancer classification
- Cancer-related gene regulation
- DNA and Nucleic Acid Chemistry
- Immune Cell Function and Interaction
- Cancer Cells and Metastasis
- Genomics and Phylogenetic Studies
- Cancer-related molecular mechanisms research
- Salivary Gland Tumors Diagnosis and Treatment
- Advanced Breast Cancer Therapies
- Protein Degradation and Inhibitors
- T-cell and B-cell Immunology
- Atherosclerosis and Cardiovascular Diseases
- Ferroptosis and cancer prognosis
- Genetics, Bioinformatics, and Biomedical Research
- Neonatal Respiratory Health Research
- Metabolism, Diabetes, and Cancer
University of Virginia
2017-2025
Office of Public Health Genomics
2017-2024
University of Virginia Cancer Center
2017-2024
Shandong Academy of Sciences
2024
Qilu University of Technology
2024
University of Alabama at Birmingham
2023
Dana-Farber Cancer Institute
2012-2022
Urology of Virginia
2021
Harvard University
2013-2018
Charlottesville Medical Research
2018
Chromatin states are the key to gene regulation and cell identity. immunoprecipitation (ChIP) coupled with high-throughput sequencing (ChIP-Seq) is increasingly being used map epigenetic across genomes of diverse species. modification profiles frequently noisy diffuse, spanning regions ranging from several nucleosomes large domains multiple genes. Much early work on identification ChIP-enriched for ChIP-Seq data has focused identifying localized regions, such as transcription factor binding...
Chromatin immunoprecipitation, DNase I hypersensitivity and transposase-accessibility assays combined with high-throughput sequencing enable the genome-wide study of chromatin dynamics, transcription factor binding gene regulation. Although rapidly accumulating publicly available ChIP-seq, DNase-seq ATAC-seq data are a valuable resource for systematic investigation regulation processes, lack standardized curation, quality control analysis procedures have hindered extensive reuse these data....
The main oncogenic driver in T-lymphoblastic leukemia is NOTCH1, which activates genes by forming chromatin-associated Notch transcription complexes. Gamma-secretase-inhibitor treatment prevents NOTCH1 nuclear localization, but most with NOTCH1-binding sites are insensitive to gamma-secretase inhibitors. Here, we demonstrate that fewer than 10% of show dynamic changes occupancy when cells toggled between the Notch-on and -off states inhibiters. Dynamic functional, being highly associated...
Abstract ENCODE comprises thousands of functional genomics datasets, and the encyclopedia covers hundreds cell types, providing a universal annotation for genome interpretation. However, particular applications, it may be advantageous to use customized annotation. Here, we develop such custom by leveraging advanced assays, as eCLIP, Hi-C, whole-genome STARR-seq on number data-rich types. A key aspect this is comprehensive experimentally derived networks both transcription factors RNA-binding...
Significance The protooncogene c-Myc (Myc) is an oncogenic driver in many cancers, but difficult to target directly with drugs. An alternative strategy use drugs that inhibit factors regulate Myc expression. Notch drives expression most T-cell leukemias, clinical trials of inhibitors have been disappointing, possibly because cells emerge express a Notch-independent fashion. Here we identify the genomic switches Notch-inhibitor–sensitive and –resistant states. Our findings suggest inhibitor...
Programmed genetic rearrangements in lymphocytes require transcription at antigen receptor genes to promote accessibility for initiating double-strand break (DSB) formation critical DNA recombination and repair. Here, we showed that activated B cells deficient the PTIP component of MLL3 (mixed-lineage leukemia 3)-MLL4 complex display impaired trimethylation histone 3 lysine 4 (H3K4me3) initiation downstream switch regions immunoglobulin heavy-chain (Igh) locus, leading defective class...
Abstract Next-generation sequencing was used to identify Notch mutations in a large collection of diverse solid tumors. NOTCH1 and NOTCH2 rearrangements leading constitutive receptor activation were confined triple-negative breast cancers (TNBC; 6 66 tumors). TNBC cell lines with associated high levels activated (N1-ICD) sensitive the gamma-secretase inhibitor (GSI) MRK-003, both alone combination paclitaxel, vitro vivo, whereas resistant GSI. Immunohistochemical staining N1-ICD xenografts...
Abstract Cancer results from a breakdown of normal gene expression control, so the study regulation is critical to cancer research. To gain insight into transcriptional and epigenetic factors regulating abnormal patterns in cancers, we developed Cistrome web resource (http://cistrome.org/CistromeCancer/). We conducted systematic integration modeling over 10,000 tumor molecular profiles The Genome Atlas (TCGA) with 23,000 ChIP-seq chromatin accessibility our collection. include reconstruction...
Abstract Background Transcription factor binding, histone modification, and chromatin accessibility studies are important approaches to understanding the biology of gene regulation. ChIP-seq DNase-seq have become standard techniques for studying protein-DNA interactions respectively, comprehensive quality control (QC) analysis tools critical extracting most value from these assay types. Although many QC been reported, few combine data in a unified framework with unbiased reference metrics....
A stringent control of homeostasis is critical for functional maintenance and survival neurons. In the mammalian retina, basic motif leucine zipper transcription factor NRL determines rod versus cone photoreceptor cell fate activates expression many rod-specific genes. Here, we report an integrated analysis NRL-centered gene regulatory network by coupling chromatin immunoprecipitation followed high-throughput sequencing (ChIP–Seq) data from Illumina ABI platforms with global profiling in...
Abstract Summary Identification of functional transcription factors that regulate a given gene set is an important problem in regulation studies. Conventional approaches for identifying factors, such as DNA sequence motif analysis, are unable to predict binding specific and not sensitive enough detect at distal enhancers. Here, we present analysis (BART), novel computational method software package predicting query or associate with genomic profile, based on more than 6000 existing ChIP-seq...