A5026240520- Alzheimer's disease research and treatments
- Epigenetics and DNA Methylation
- Dementia and Cognitive Impairment Research
- RNA modifications and cancer
- Medical Imaging and Pathology Studies
- Thyroid and Parathyroid Surgery
- Genomics and Chromatin Dynamics
- Genomics and Rare Diseases
- Histone Deacetylase Inhibitors Research
- Protein Degradation and Inhibitors
- Cancer Genomics and Diagnostics
- Parkinson's Disease Mechanisms and Treatments
- Bioinformatics and Genomic Networks
- Parathyroid Disorders and Treatments
- Neurological diseases and metabolism
- Amyotrophic Lateral Sclerosis Research
- Prion Diseases and Protein Misfolding
- Neurogenetic and Muscular Disorders Research
- Peptidase Inhibition and Analysis
- Peroxisome Proliferator-Activated Receptors
- Pregnancy and preeclampsia studies
- Nutrition, Genetics, and Disease
- Trace Elements in Health
- Genetic Syndromes and Imprinting
- RNA Research and Splicing
Washington University in St. Louis
2014-2021
University of California, Los Angeles
2012-2019
UCLA Health
2013-2015
The WashU Epigenome Browser (https://epigenomegateway.wustl.edu/) provides visualization, integration and analysis tools for epigenomic datasets. Since 2010, it has provided the scientific community with data from large consortia including Roadmap Epigenomics ENCODE projects. Recently, we refactored codebase, redesigned user interface, developed various novel features. New features include: (i) visualization using virtual reality (VR), which implications in biology education study of 3D...
Rare mutations in the gene encoding for tau (MAPT, microtubule-associated protein tau) cause frontotemporal dementia-spectrum (FTD-s) disorders, including FTD, progressive supranuclear palsy (PSP) and corticobasal syndrome, a common extended haplotype spanning across MAPT locus is associated with increased risk of PSP Parkinson's disease.We identified rare variant (p.A152T) patient clinical diagnosis assessed its frequency multiple independent series patients neurodegenerative conditions...
Uncovering mechanisms of epigenome evolution is an essential step towards understanding the different cellular phenotypes. While studies have confirmed DNA methylation as a conserved epigenetic mechanism in mammalian development, little known about conservation tissue-specific genome-wide patterns.Using comparative epigenomics approach, we identified and compared patterns rat against those mouse human across three shared tissue types. We that differentially methylated regions are strongly...
Little is known about how changes in DNA methylation mediate risk for human diseases including dementia. Analysis of genome-wide patterns patients with two forms tau-related dementia--progressive supranuclear palsy (PSP) and frontotemporal dementia (FTD)--revealed significant differentially methylated probes (DMPs) versus unaffected controls. Remarkably, DMPs PSP were clustered within the 17q21.31 region, previously to harbor major genetic factor PSP. We identified replicated a...
Previous studies have indicated a heritable component of the etiology neurodegenerative diseases such as Alzheimer disease (AD), frontotemporal dementia (FTD), and progressive supranuclear palsy (PSP). However, few examined contribution low-frequency coding variants on genome-wide level.To identify that affect susceptibility to AD, FTD, PSP.We used Illumina HumanExome BeadChip array genotype large number (most which are variants) in cohort patients with (224 168 48 PSP) 224 control...
Transcriptional changes in Friedreich's ataxia (FRDA), a rare and debilitating recessive Mendelian neurodegenerative disorder, have been studied affected but inaccessible tissues-such as dorsal root ganglia, sensory neurons cerebellum-in animal models or small patient series. However, transcriptional induced by FRDA peripheral blood, readily accessible tissue, not characterized large sample. We used differential expression, association with disability stage, network analysis enrichment to...
Abstract Accurate indel calling plays an important role in precision medicine. A benchmarking set is essential for thoroughly evaluating the performance of bioinformatics pipelines. reference sample with a known-positive variants was developed FDA-led Sequencing Quality Control Phase 2 (SEQC2) project, but known indels were limited. This project sought to provide enriched that would be more translationally relevant by focusing on additional cancer related regions. thorough manual review...
Heritability of Alzheimer's disease (AD) is estimated at 74% and genetic contributors have been widely sought. The ε4 allele apolipoprotein E (APOE) remains the strongest common risk factor for AD, with numerous other variants contributing only modest disease. Variability in clinical presentation which typically amnestic (AmnAD) but can less commonly involve visuospatial, language and/or dysexecutive syndromes (atypical or AtAD), further complicates analyses. Taking a multi-locus approach...
Patients with frontotemporal lobar degeneration (FTLD) can show superimposed amyloid pathology, though the impact of on clinical presentation FTLD is not well characterized. This cross-sectional case–control study compared features, fluorodeoxyglucose-positron emission tomography metabolism and gray matter volume loss in 30 patients familial whom status was confirmed autopsy or Pittsburgh compound B-PET. Compared to amyloid-negative patients, amyloid-positive performed significantly worse...
Abstract The role of peripheral inflammation in dementia is an important but complex topic. We present here the largest cohort blood gene expression data ever assembled from patients with and matching controls. Importantly, this includes individuals a diverse set disorders, including Alzheimer’s Disease (AD), mild cognitive impairment (MCI), multiple disorders within frontotemporal (FTD) spectrum. found strong transcriptional evidence innate immune inflammatory response, mediated by...
Abstract Introduction: To help guide treatment decisions and enable clinical trial matching for cancer patients, tissue-based comprehensive genomic profiling (CGP) is an essential precision oncology tool. Liquid biopsy may be used as a complementary approach to assess tumor-specific DNA alterations circulating in the blood when tissue limited or unavailable. PGDx’s elio™ plasma complete next-generation-sequencing (NGS), cell-free (cfDNA) CGP assay that identifies clinically significant...
Alzheimer's disease (AD) is characterized by the accumulation of amyloid- β (Aβ) in brain. The mechanism which amyloid precursor protein (APP) proteolyzed to generate Aβ well understood; however, role that other genes play APP trafficking and production, clearance, aggregation are poorly understood.APOE4 a major risk factor for late onset AD produces genotype-specific differences clearance rates. However, APOE4 only accounts 50% genetic associated with AD. We have recently identified several...
The heritability of late-onset Alzheimer's disease (LOAD) is estimated to be as high 80%. Large-scale genome-wide studies have identified a small subset genes that explains only fraction LOAD heritability. Alternative approaches investigating intermediate phenotypes may necessary advance our understanding Studies in peripheral blood might prove useful, ∼80% brain-expressed are also expressed cells, and gene expression changes already been described AD. ImaGene study single-site longitudinal...
OBJECTIVE: To test the hypothesis that PCH1-causing mutations in EXOSC3 disrupts normal exosome function RNA processing and turnover. BACKGROUND: dysregulation is emerging as an important etiology of neurodegeneration a broad range neurological disorders including spinal muscular atrophy, amyotrophic lateral sclerosis, spinocerebellar ataxia type 36 affect motor neurons cerebellar neurons. Pervasive genomewide transcription further underscores importance regulation metabolism. We recently...
OBJECTIVE: To investigate the associations between cortical atrophy and top 10 susceptibility genes for late onset AD.