A5001964307- Neuroinflammation and Neurodegeneration Mechanisms
- Bioinformatics and Genomic Networks
- Alzheimer's disease research and treatments
- Genetic Associations and Epidemiology
- Inflammation biomarkers and pathways
- RNA Research and Splicing
- Mitochondrial Function and Pathology
- Epigenetics and DNA Methylation
- Neurological Disease Mechanisms and Treatments
- MicroRNA in disease regulation
- Peroxisome Proliferator-Activated Receptors
- Single-cell and spatial transcriptomics
- Biological Research and Disease Studies
- Nuclear Structure and Function
- Circular RNAs in diseases
- Genomics and Rare Diseases
- Biotin and Related Studies
- Distributed Control Multi-Agent Systems
- Moyamoya disease diagnosis and treatment
- Genetic Syndromes and Imprinting
- melanin and skin pigmentation
- Genetic Mapping and Diversity in Plants and Animals
- Zebrafish Biomedical Research Applications
- Ophthalmology and Visual Impairment Studies
- Corneal surgery and disorders
Washington University in St. Louis
2012-2023
Hope Center for Neurological Disorders
2018-2020
Weihai Science and Technology Bureau
2017
State Street (United States)
2013
Purdue University West Lafayette
2012
Common variants in the microglia-specific MS4A gene cluster modify risk for late-onset Alzheimer’s disease and modulate extracellular soluble TREM2.
Alzheimer’s disease (AD) is the most common form of dementia. This neurodegenerative disorder associated with neuronal death and gliosis heavily impacting cerebral cortex. AD has a substantial but heterogeneous genetic component, presenting both Mendelian complex architectures. Using bulk RNA-seq from parietal lobes deconvolution methods, we previously reported that brains exhibiting different architecture exhibit cellular proportions. Here, sought to directly investigate brain changes in...
Alcohol exposure triggers changes in gene expression and biological pathways human brain. We explored alterations the Pre-Frontal Cortex (PFC) of 65 alcoholics 73 controls European descent, identified 129 genes that showed altered (FDR < 0.05) subjects with alcohol dependence. Differentially expressed were enriched for related to interferon signaling Growth Arrest DNA Damage-inducible 45 (GADD45) signaling. A coexpression module (thistle2) by weighted co-expression network analysis (WGCNA)...
Low frequency coding variants in TREM2 are associated with Alzheimer disease (AD) risk and cerebrospinal fluid (CSF) protein levels different between AD cases controls. Similarly, variant carriers also exhibit differential CSF levels. has three alternative transcripts, but most of the functional studies only model longest transcript. No have analyzed expression or splicing brains from cognitively normal individuals. We wanted to determine whether there was sporadic-AD versus AD-TREM2 vs sex-...
Phenylthiourea (PTU) is commonly used for inhibiting melanization of zebrafish embryos. In this study, the standard treatment with 0.2 mM PTU was demonstrated to specifically reduce eye size in larval fish starting at three days post-fertilization. This effect likely result a reduction retinal and lens PTU-treated eyes not related inhibition. because tyr, genetic mutant tyrosinase whose activity inhibited treatment, reduced. As contains thiocarbamide group which presented many goitrogens,...
Abstract Mutations in the microtubule-associated protein tau ( MAPT ) gene cause autosomal dominant frontotemporal lobar degeneration with inclusions (FTLD-tau). p.R406W carriers present clinically progressive memory loss and neuropathologically neuronal glial tauopathy. However, pathogenic events triggered by expression of mutant remain poorly understood. To identify genes pathways that are dysregulated FTLD-tau, we performed transcriptomic analyses induced pluripotent stem cell...
Alzheimer's disease (AD) is characterized by neuronal loss and astrocytosis in the cerebral cortex. However, specific effects that pathological mutations coding variants associated with AD have on cellular composition of brain are often ignored. We developed optimized a cell-type-specific expression reference panel employed digital deconvolution methods to determine distribution three independent transcriptomic studies. found astrocyte relative proportions differ between healthy diseased...
Abstract Expression quantitative trait loci (eQTL) mapping has successfully resolved some genome-wide association study (GWAS) for complex traits 1–6 . However, there is a need implementing additional “omic” approaches to untangle and provide biological context GWAS signals. We generated detailed landscape of the genomic architecture protein levels in multiple neurologically relevant tissues (brain, cerebrospinal fluid (CSF) plasma), by profiling thousands proteins large well-characterized...
Rare variants in PLCG2 (p.P522R), ABI3 (p.S209F), and TREM2 (p.R47H, p.R62H) have been associated with late onset Alzheimer's disease (LOAD) risk Caucasians. After the initial report, several studies found positive results cohorts of different ethnic background phenotype.
Abstract Alzheimer Disease (AD) is the most common form of dementia. This neurodegenerative disorder associated with neuronal death and gliosis heavily impacting cerebral cortex. AD has a substantial but heterogeneous genetic component, presenting both Mendelian complex architectures. Using bulk RNA-seq from parietal lobes deconvolution methods, we previously reported that brains exhibiting different architecture exhibit cellular proportions. Here, sought to directly investigate brain...
Abstract Soluble triggering receptor expressed on myeloid cells 2 (sTREM2) levels in the cerebrospinal fluid (CSF) have been associated with Alzheimer disease (AD) status. TREM2 plays a critical role microglial activation, survival, and phagocytosis; however, pathophysiological of sTREM2 AD is not well understood. Understanding may help reveal biological mechanisms underlying identify novel therapeutic targets. We performed genome-wide association study (GWAS) to genetic modifiers CSF...
Abstract Understanding the tissue-specific genetic architecture of protein levels is instrumental to understand biology health and disease. We generated a genomic atlas in multiple neurologically relevant tissues (380 brain, 835 cerebrospinal fluid (CSF) 529 plasma), by profiling thousands proteins (713 CSF, 931 plasma 1079 brain) large well-characterized cohort. identified 274, 127 32 quantitative loci (pQTL) for brain respectively. cis-pQTL were more likely be shared across but trans-pQTL...
Abstract Alzheimer’s disease (AD) is characterized by neuronal loss and astrocytosis in the cerebral cortex. However, effects of brain cellular composition are often ignored high-throughput molecular studies. We developed optimized a cell-type specific expression reference panel employed digital deconvolution methods to determine distribution three independent transcriptomic found that astrocyte proportions differ between healthy diseased brains also among AD cases carry genetic risk...
ABSTRACT Alcohol exposure triggers changes in gene expression and biological pathways human brain. We explored alterations the Pre-Frontal Cortex (PFC) of 65 alcoholics 73 controls European descent, identified 129 genes that showed altered (FDR < 0.05) subjects with alcohol dependence. Differentially expressed were enriched for related to interferon signaling Growth Arrest DNA Damage-inducible 45 (GADD45) signaling. A coexpression module (thistle2) by weighted co-expression network...
Abstract Background In previous studies, we observed decreased neuronal and increased astrocyte proportions in AD cases parietal brain cortex by using a deconvolution method for bulk RNA-seq. These findings suggested that genetic risk factors associated with etiology have specific effect the cellular composition of brains. The goal this study is to investigate if there are determinants cell compositions. Methods Using type inferred from transcriptome as disease status proxy, performed...
Abstract Alzheimer’s disease (AD) is characterized by the accumulation of amyloid-β (Aβ) plaques and neurofibrillary tangles in brain. AD also result complex genetic architecture that can be leveraged to understand pathways central processes. We have previously identified coding variants phospholipase D3 ( PLD3 ) gene double late-onset risk. However, mechanism which impacts risk unknown. One variant, p.A442A, disrupts a splicing enhancer-binding site reduces human brains. Using...
Abstract Background Amyloid‐beta (Aβ) plaque formation is a well‐established hallmark for Alzheimer’s disease (AD). However, the processes behind are not understood. Previous work from our group identified rare coding variants PLD3, with one variant in particular, p.A442A, disrupting splicing enhancer binding site within mRNA transcript. In this study, we present findings that PLD3 regulates Aβ clearance brain through both cell autonomous and non‐autonomous means. Method To replicate effect...