Xylena Reed
A5055082420- Parkinson's Disease Mechanisms and Treatments
- Neurological diseases and metabolism
- Lysosomal Storage Disorders Research
- RNA regulation and disease
- Genomics and Chromatin Dynamics
- CRISPR and Genetic Engineering
- Neuroinflammation and Neurodegeneration Mechanisms
- Nuclear Receptors and Signaling
- RNA modifications and cancer
- Amyotrophic Lateral Sclerosis Research
- Alzheimer's disease research and treatments
- Genetic Associations and Epidemiology
- Genomic variations and chromosomal abnormalities
- Plant Gene Expression Analysis
- Genomics and Rare Diseases
- Cellular transport and secretion
- Pluripotent Stem Cells Research
- S100 Proteins and Annexins
- Plant biochemistry and biosynthesis
- RNA Research and Splicing
- Autism Spectrum Disorder Research
- Genetics and Neurodevelopmental Disorders
- Cancer-related molecular mechanisms research
- Genomics and Phylogenetic Studies
- Carbohydrate Chemistry and Synthesis
National Institutes of Health
2018-2024
National Institute on Aging
2016-2024
National Institute of Neurological Disorders and Stroke
2023-2024
Institute on Aging
2023-2024
Genomics England
2021
Johns Hopkins Medicine
2011-2018
Johns Hopkins University
2011-2018
University of Washington
2011
National Institute of Dental and Craniofacial Research
2010
The maintenance of a progenitor cell population as reservoir undifferentiated cells is required for organ development and regeneration. However, the mechanisms by which epithelial are maintained during organogenesis poorly understood. We report that removal parasympathetic ganglion in mouse explant culture decreased number morphogenesis keratin 5-positive cells. These effects were rescued with an acetylcholine analog. demonstrate signaling, via muscarinic M1 receptor epidermal growth factor...
Parkinson's disease is a genetically complex disorder. Multiple genes have been shown to contribute the risk of disease, and currently 90 independent variants identified by genome-wide association studies. Thus far, number (including SNCA, LRRK2, GBA) contain variability across spectrum frequency effect, from rare, highly penetrant common alleles with small effect sizes. Variants in GBA, encoding enzyme glucocerebrosidase, are associated Lewy body diseases such as dementia. These variants,...
<h3>Importance</h3> Substantial genome-wide association study (GWAS) work in Parkinson disease (PD) has led to the discovery of an increasing number loci shown reliably be associated with increased risk disease. Improved understanding underlying genes and mechanisms at these will key pathogenesis PD. <h3>Objective</h3> To investigate what genomic processes underlie sporadic <h3>Design Setting</h3> This genetic used bioinformatic tools Coloc transcriptome-wide (TWAS) integrate PD case-control...
Parkinson's disease is a neurodegenerative movement disorder that currently has no disease-modifying treatment, partly owing to inefficiencies in drug target identification and validation. We use Mendelian randomization investigate over 3,000 genes encode druggable proteins predict their efficacy as targets for disease. expression protein quantitative trait loci mimic exposure medications, we examine the causal effect on risk (in two large cohorts), age at onset progression. propose 23...
Studies of multiple neurodegenerative disorders have identified many genetic variants that are associated with risk disease throughout a lifetime. For example, Parkinson’s (PD) is attributed in part to both coding mutations the leucine-rich repeat kinase 2 ( LRRK2 ) gene and common noncoding variation 5′ region locus, as by genome-wide association studies (GWAS). However, mechanisms linking GWAS pathogenicity largely unknown. Here, we found influence PD-associated on expression specifically...
Abstract Mitochondrial dysfunction has been implicated in the etiology of monogenic Parkinson’s disease (PD). Yet role that mitochondrial processes play most common form disease; sporadic PD, is yet to be fully established. Here, we comprehensively assessed function-associated genes PD by leveraging improvements scale and analysis GWAS data with recent advances our understanding genetics disease. We calculated a mitochondrial-specific polygenic risk score (PRS) showed cumulative small effect...
Abstract Parkinson’s disease (PD), with its characteristic loss of nigrostriatal dopaminergic neurons and deposition α-synuclein in neurons, is often considered a neuronal disorder. However, recent years substantial evidence has emerged to implicate glial cell types, such as astrocytes microglia. In this study, we used stratified LD score regression expression-weighted cell-type enrichment together several brain-related cell-type-specific genomic annotations connect human PD findings...
Abstract Background Parkinson's disease (PD) is a neurodegenerative with an often complex component identifiable by genome‐wide association studies. The most recent large‐scale PD studies have identified more than 90 independent risk variants for and progression across 80 genomic regions. One major challenge in current genomics the identification of causal gene(s) variant(s) at each study locus. objective was to create tool that would display data relevant loci provide guidance...
Abstract Background Parkinson’s disease (PD) is a neurodegenerative movement disorder affecting 1–5% of the general population for which neither effective cure nor early diagnostic tools are available that could tackle pathology in phase. Here we report multi-stage procedure to identify candidate genes likely involved etiopathogenesis PD. Methods The study includes discovery stage based on analysis whole exome data from 26 dominant late onset PD families, validation performed 1542...
The Foundational Data Initiative for Parkinson Disease (FOUNDIN-PD) is an international collaboration producing fundamental resources disease (PD). FOUNDIN-PD generated a multi-layered molecular dataset in cohort of induced pluripotent stem cell (iPSC) lines differentiated to dopaminergic (DA) neurons, major affected type PD. were derived from the Parkinson's Progression Markers study, which included participants with PD carrying monogenic variants, variants intermediate effects, and...
Identification of genetic risk factors for Parkinson disease (PD) has to date been primarily limited the study single nucleotide variants, which only represent a small fraction variation in human genome. Consequently, causal variants most PD are not known. Here we focused on structural (SVs), major source We aimed discover SVs associated with by performing first large-scale characterization PD.
<h3>Importance</h3> Pathogenic variants in<i>LRRK2</i>are a relatively common genetic cause of Parkinson disease (PD). Currently, the molecular mechanism underlying is unknown, and gain loss function (LOF) models pathogenesis have been postulated.<i>LRRK2</i>variants are reported to result in enhanced phosphorylation substrates increased cell death. However, double knockout of<i>Lrrk2</i>and its homologue<i>Lrrk1</i>results neurodegeneration mouse model, suggesting that may occur by LOF....
Alterations in the p38 mitogen-activated protein kinases (MAPKs) play an important role pathogenesis of dementia with Lewy bodies (DLB) and Parkinson's disease (PD). Activation p38α MAPK isoform mislocalization p38γ are associated neuroinflammation synaptic degeneration DLB PD. Therefore, we hypothesized that might be neuronal distribution dysfunction these diseases. To test this hypothesis, treated vitro cellular vivo mouse models DLB/PD SKF-86002, a compound attenuates inflammation by...
Long-read sequencing technologies substantially overcome the limitations of short-reads but to date have not been considered as feasible replacement at scale due a combination being too expensive, scalable enough, or error-prone. Here, we develop an efficient and wet lab computational protocol for Oxford Nanopore Technologies (ONT) long-read that seeks provide genuine alternative large-scale genomics projects. We applied our cell lines brain tissue samples part pilot project NIH Center...
We take a comprehensive approach to the study of regulatory control gene expression in melanocytes that proceeds from large-scale enhancer discovery facilitated by ChIP-seq; rigorous validation silico, vitro, and vivo; finally use machine learning elucidate vocabulary with genome-wide predictive power. identify 2489 putative melanocyte loci mouse genome ChIP-seq for EP300 H3K4me1. demonstrate these enhancers are evolutionarily constrained, enriched sequence motifs predicted bind key...
Abstract Background The ERBB3 gene is essential for the proper development of neural crest (NC) and its derivative populations such as Schwann cells. As with all cell fate decisions, transcriptional regulatory control plays a significant role in progressive restriction specification NC derived lineages during development. However, little known about sequences mediating regulation or factors that bind them. Results In this study we identified three enhancers at locus evaluated their potential...
Abstract Genome-wide association studies have generated an increasing number of common genetic variants associated with neurological and psychiatric disease risk. An improved understanding the control gene expression in human brain is vital considering this likely modus operandum for many causal variants. However, sampling complexities limit explanatory power brain-related quantitative trait loci (eQTL) allele-specific (ASE) signals. We address this, using paired genomic transcriptomic data...
Understanding the genetic mechanisms underlying diseases in ancestrally diverse populations is a critical step towards realization of global application precision medicine. The African and admixed enable mapping complex traits given their greater levels diversity, extensive population substructure, distinct linkage disequilibrium patterns.Here we perform comprehensive genome-wide assessment Parkinson's disease (PD) 197,918 individuals (1,488 cases; 196,430 controls) ancestry, characterizing...
Abstract INTRODUCTION Variants of uncertain significance (VUS) surged with affordable genetic testing, posing challenges for determining pathogenicity. We examine the pathogenicity a novel VUS P93S in Annexin A11 (ANXA11) – an amyotrophic lateral sclerosis/frontotemporal dementia‐associated gene corticobasal syndrome kindred. Established ANXA11 mutations cause aggregation, altered lysosomal‐RNA granule co‐trafficking, and transactive response DNA binding protein 43 kDa (TDP‐43)...