A5033581206- Genetic Associations and Epidemiology
- Genomics and Chromatin Dynamics
- interferon and immune responses
- Epigenetics and DNA Methylation
- SARS-CoV-2 and COVID-19 Research
- RNA Research and Splicing
- Immune responses and vaccinations
- Bioinformatics and Genomic Networks
- RNA modifications and cancer
- Immune Cell Function and Interaction
- Cancer-related molecular mechanisms research
- T-cell and B-cell Immunology
- Cancer-related gene regulation
- Gene expression and cancer classification
- Neuroinflammation and Neurodegeneration Mechanisms
- Alzheimer's disease research and treatments
- RNA regulation and disease
- Peroxisome Proliferator-Activated Receptors
- Bone health and osteoporosis research
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Curcumin's Biomedical Applications
- Circadian rhythm and melatonin
- Adipose Tissue and Metabolism
- Birth, Development, and Health
- Kruppel-like factors research
Children's Hospital of Philadelphia
2016-2024
Shandong First Medical University
2024
Weifang Medical University
2024
Affiliated Hospital of Shandong University of Traditional Chinese Medicine
2024
Shandong University
2010-2023
Shandong Provincial QianFoShan Hospital
2022-2023
University of Pennsylvania
2003-2020
Philadelphia University
2018-2019
Shandong Eye Hospital
2011
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...
Bone accrual impacts lifelong skeletal health, but genetic discovery has been primarily limited to cross-sectional study designs and hampered by uncertainty about target effector genes. Here, we capture this dynamic phenotype modeling longitudinal bone across 11,000 scans in a cohort of healthy children adolescents, followed genome-wide association studies (GWAS) variant-to-gene mapping with functional follow-up.
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...
The central clock is generally thought to provide timing information for rest/activity but not otherwise participate in regulation of these states. To test the hypothesis that genes are components molecular also regulate rest, authors quantified duration and intensity consolidated rest activity four viable Drosophila mutations lead arrhythmic locomotor behavior pdf mutant lacks pigment dispersing factor, an output neuropeptide. Only cycle ( cyc 0 ¹) Clock Clk Jrk ) mutants had abnormalities...
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...
The ch12q13 locus is among the most significant childhood obesity loci identified in genome-wide association studies. This resides a non-coding region within FAIM2; thus, underlying causal variant(s) presumably influence disease susceptibility via cis-regulation. We implicated rs7132908 as putative variant by leveraging our in-house 3D genomic data and public domain datasets. Using luciferase reporter assay, we observed allele-specific cis-regulatory activity of immediate harboring...
Abstract Osteoblast differentiation of bone marrow-derived human mesenchymal stem cells (hMSC) can be induced by stimulation with canonical Notch ligand, Jagged1, or morphogenetic proteins (BMPs). However, it remains elusive how these two pathways lead to the same phenotypic outcome. Since Runx2 is regarded as a master regulator osteoblastic differentiation, we targeted siRNA in hMSC. This abrogated both Jagged1 and BMP2 mediated confirming fundamental role for Runx2. while BMP 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...
To accommodate the large cells following zygote formation, early blastomeres employ modified cell divisions. Karyomeres are one such modification, mitotic intermediates wherein individual chromatin masses surrounded by nuclear envelope; karyomeres then fuse to form a single mononucleus. We identified brambleberry, maternal-effect zebrafish mutant that disrupts karyomere fusion, resulting in formation of multiple micronuclei. As form, Brambleberry protein localizes envelope, with prominent...
Abstract Background Insulin resistance (IR) in hepatocytes endangers human health, and frequently results the development of non-alcoholic fatty liver disease (NAFLD). Research on m 6 A methylation RNA molecules has gained popularity recent years; however, molecular mechanisms regulating processes modification IR are not known. The cytochrome P450 (CYP450) enzyme system, which is mainly found liver, associated with pathogenesis NAFLD. However, few studies have been conducted CYP450 related...
Background & AimsInflammatory bowel disease (IBD) is a polygenic disorder characterized principally by dysregulated inflammation impacting the gastrointestinal tract. However, there also increasing evidence for clinical association with stress and depression. Given role of hypothalamus in responses pathogenesis depression, useful insights could be gleaned from understanding its genetic IBD.MethodsWe conducted correlation analyses on publicly available genome-wide study summary statistics...
Forward genetic screens remain at the forefront of biology as an unbiased approach for discovering and elucidating gene function organismal molecular level. Past mutagenesis targeting maternal-effect genes identified a broad spectrum phenotypes ranging from defects in oocyte development to embryonic patterning. However, earlier vertebrate did not reach saturation, anticipated classes were uncovered, technological limitations made it difficult pinpoint causal gene. In this study, we performed...
TSH/TSHR signaling plays a role in the regulation of lipid metabolism adipocytes. However, precise mechanisms are not known. In present study, we determined effect TSH on fatty acid synthase (FASN) expression, and explored underlying mechanisms. vitro, reduced FASN expression both mRNA protein levels mature adipocytes was accompanied by kinase A (PKA) activation, cAMP‐response element binding (CREB) phosphorylation, as well extracellular signal‐regulated 1/2 (ERK1/2) c‐Jun NH 2 ‐terminal...
Abstract The IL1A and IL1B genes lie in close proximity on chromosome 2 near the gene for their natural inhibitor, IL1RN. Despite diverse functions, they are all three inducible through TLR4 signaling but with distinct kinetics. This study analyzed transcriptional induction kinetics, looping, enhancer RNA production to understand regulation of these human cells. IL1A, IL1B, IL1RN were rapidly induced after stimulation LPS; however, mRNA was less inhibitable by iBET151, suggesting it does not...
<i>TCF7L2</i> is located at one of the most strongly associated type 2 diabetes loci reported to date. We previously that abundant member a specific protein complex bind across presumed causal variant this locus, rs7903146, was poly [ADP-ribose] polymerase 1 (PARP-1). analyzed impact PARP-1 inhibition on <i>C. elegans</i> health in setting hyperglycemia and glucose-stimulated GLP-1 secretion human intestinal cells. Given high glucose concentrations progressively shorten lifespan elegans</i>,...
<i>Aim:</i> Vestibular hair cell loss in response to different stimuli may be attributable the occurrence of apoptosis, which apoptosis-inducing factor (AIF) is an important regulator mediating apoptotic process independent caspases. This study was designed investigate possible involvement AIF gentamicin (GM)-induced vestibular death. <i>Methods:</i> organs from postnatal day 3 or 4 rats were maintained tissue culture and exposed 2 mg/ml GM for up 72 h. viability...