A5070459086- Systemic Lupus Erythematosus Research
- RNA Research and Splicing
- RNA modifications and cancer
- T-cell and B-cell Immunology
- IL-33, ST2, and ILC Pathways
- Viral-associated cancers and disorders
- Dermatology and Skin Diseases
- Eosinophilic Esophagitis
- Lymphoma Diagnosis and Treatment
- Immune Cell Function and Interaction
- Genomics and Chromatin Dynamics
- Cancer-related gene regulation
- interferon and immune responses
- Muscle Physiology and Disorders
- Inflammatory Bowel Disease
- Hippo pathway signaling and YAP/TAZ
- Celiac Disease Research and Management
- Microtubule and mitosis dynamics
- Wnt/β-catenin signaling in development and cancer
- Genetic Associations and Epidemiology
- Renal Diseases and Glomerulopathies
- CRISPR and Genetic Engineering
- Eosinophilic Disorders and Syndromes
- Antimicrobial Peptides and Activities
- Cellular transport and secretion
Cincinnati Children's Hospital Medical Center
2019-2025
University of Cincinnati
2023-2024
University of California, Davis
2023
University of California System
2023
Autoimmune Technologies (United States)
2020-2022
University of Cincinnati Medical Center
2020-2021
Louisiana State University Health Sciences Center New Orleans
2010-2020
Non-alcoholic fatty liver disease (NAFLD) is a common chronic illness with genetically heterogeneous background that can be accompanied by considerable morbidity and attendant health care costs. The pathogenesis progression of NAFLD complex many unanswered questions. We conducted genome-wide association studies (GWASs) using both adult pediatric participants from the Electronic Medical Records Genomics (eMERGE) Network to identify novel genetic contributors this condition.First, natural...
Abstract Genome-wide association studies of Systemic Lupus Erythematosus (SLE) nominate 3073 genetic variants at 91 risk loci. To systematically screen these for allelic transcriptional enhancer activity, we construct a massively parallel reporter assay (MPRA) library comprising 12,396 DNA oligonucleotides containing the genomic context around every allele each SLE variant. Transfection into Epstein-Barr virus-transformed B cell line GM12878 reveals 482 with 51 showing genotype-dependent...
Myeloid lineage cells use TLRs to recognize and respond diverse microbial ligands. Although unique transcription factors dictate the outcome of specific TLR signaling, whether lineage-specific differences exist further modulate quality TLR-induced inflammation remains unclear. Comprehensive analysis global gene in human monocytes, monocyte-derived macrophages, dendritic stimulated with various ligands identifies multiple lineage-specific, TLR-responsive programs. Monocytes are...
Transcription factors read the genome, fundamentally connecting DNA sequence to gene expression across diverse cell types. Determining how, where, and when TFs bind chromatin will advance our understanding of regulatory networks cellular behavior. The 2017 ENCODE-DREAM in vivo Transcription-Factor Binding Site ( TFBS ) Prediction Challenge highlighted value accessibility data prediction, establishing state-of-the-art methods for prediction from DNase-seq. However, more recent...
The lipogenic enzyme stearoyl CoA desaturase (SCD) plays a key role in tumor lipid metabolism and membrane architecture. SCD is often up-regulated therapeutic target cancer. Here, we report the unexpected finding that median expression of low glioblastoma relative to normal brain due hypermethylation unintentional monoallelic co-deletion with phosphatase tensin homolog (PTEN) subset patients. Cell lines from this expressed undetectable SCD, yet retained residual enzymatic activity....
Eosinophilic esophagitis (EoE) is a rare atopic disorder associated with esophageal dysfunction, including difficulty swallowing, food impaction, and inflammation, that develops in small subset of people allergies. Genome-wide association studies (GWASs) have identified 9 independent EoE risk loci reaching genome-wide significance (p < 5 × 10
The interplay between environmental and genetic factors plays a key role in the development of many autoimmune diseases. In particular, Epstein-Barr virus (EBV) is an established contributor to multiple sclerosis, lupus, other disorders. Previously, we showed that EBV nuclear antigen 2 (EBNA2) transactivating protein occupies up half risk loci for set seven To further examine mechanistic roles played by EBNA2 at these on genome-wide scale, globally examined gene expression, chromatin...
Abstract Background There are two major genetic types of Epstein-Barr Virus (EBV): type 1 (EBV-1) and 2 (EBV-2). EBV functions by manipulating gene expression in host B cells, using virus-encoded regulatory proteins including Nuclear Antigen (EBNA2). While EBNA2 is known to interact with human transcription factors (hTFs) such as RBPJ, EBF1, SPI1 (PU.1), shares only ~ 50% amino acid identity thus may have distinct binding partners, genome locations, functions. Results In this study, we...
Intercellular transmission of messenger RNA (mRNA) is being explored in mammalian species using immortal cell lines. Here, we uncover an intercellular mRNA transfer phenomenon that allows for the adaptation and reprogramming human primed pluripotent stem cells (hPSCs). This process induced by direct contact-mediated coculture with mouse embryonic under condition impermissible hPSC culture. Mouse-derived contents are transmitted into adapted hPSCs only coculture. Transfer-specific analysis...
Inter-cellular transmission of mRNA is being explored in mammalian species using immortal cell lines (1-3). Here, we uncover an inter-cellular transfer phenomenon that allows for the adaptation and reprogramming human primed pluripotent stem cells (hPSCs). This process induced by direct contact-mediated coculture with mouse embryonic (mESCs) under condition impermissible PSC culture. Mouse-derived contents are transmitted into adapted hPSCs only coculture. Transfer-specific analysis show...
Runt-related transcription factor 1 (Runx1) can act as both an activator and a repressor. Here we show that CRISPR-mediated deletion of Runx1 in mouse metanephric mesenchyme-derived mK4 cells results large-scale genome-wide changes to chromatin accessibility gene expression. Open regions near down-regulated loci enriched for Runx sites lose knockout cells, despite remaining Runx2-bound. Unexpectedly, upregulated genes are depleted instead Zeb binding sites. Re-expressing Zeb2 restores...
Abstract Inflammatory Bowel Disease ( IBD ) is a chronic and often debilitating autoinflammatory condition, with an increasing incidence in children. Standard-of-care therapies lead to sustained transmural healing clinical remission fewer than one-third of patients. For children, TNFα inhibition remains the only FDA-approved biologic therapy, providing even greater urgency understanding mechanisms response. Genome-wide association studies GWAS have identified 418 independent genetic risk...
Non-coding DNA variants (NCVs) impact gene expression by altering binding sites for regulatory complexes. New high-throughput methods are needed to characterize the of NCVs on We developed CASCADE (Customizable Approach Survey Complex Assembly at Elements), an array-based method profile cofactor (COF) recruitment. identifies DNA-bound transcription factor-cofactor (TF-COF) complexes in nuclear extracts and quantifies their binding. demonstrate sensitivity characterizing condition-specific...
Atopic dermatitis (AD) is one of the most common skin disorders among children. Disease etiology involves genetic and environmental factors, with 29 independent AD risk loci enriched for allele-dependent gene expression in CD4+ T cell compartments. We investigated potential epigenetic mechanisms responsible susceptibility cells. To understand differences regulatory activity peripheral blood cells AD, we measured chromatin accessibility (an assay based on transposase-accessible sequencing,...
Human cytomegalovirus (HCMV) infects up to 80% of the world's population. Here, we show that HCMV infection leads widespread changes in human chromatin accessibility and looping, with hundreds thousands genomic regions affected 48 hours after infection. Integrative analyses reveal HCMV-induced perturbation Hippo signaling through drastic reduction TEAD1 transcription factor activity. We confirm extensive concordant loss binding, active H3K27ac histone marks, looping interactions upon Our...