A5057737998- Amyotrophic Lateral Sclerosis Research
- Neurogenetic and Muscular Disorders Research
- Genetic Neurodegenerative Diseases
- RNA Research and Splicing
- Mitochondrial Function and Pathology
- Gene Regulatory Network Analysis
- Neuroscience and Neuropharmacology Research
- Full-Duplex Wireless Communications
- Tryptophan and brain disorders
- Neuroinflammation and Neurodegeneration Mechanisms
- Spinal Cord Injury Research
- Educational Robotics and Engineering
- Traumatic Brain Injury Research
- biodegradable polymer synthesis and properties
- Viral Infections and Immunology Research
- Polyomavirus and related diseases
- Genomics and Chromatin Dynamics
- RNA and protein synthesis mechanisms
- Plant Virus Research Studies
- Gene expression and cancer classification
- Prion Diseases and Protein Misfolding
Northwestern University
2018-2022
Johns Hopkins Medicine
2012-2015
Johns Hopkins University
2012-2015
National Institute of Neurological Disorders and Stroke
2014
National Institutes of Health
2014
Abstract A G4C2 hexanucleotide repeat expansion in the C9orf72 gene is most common genetic cause of ALS and FTLD (C9-ALS/FTLD) with cytoplasmic TDP-43 inclusions observed regions neurodegeneration. The accumulation repetitive RNAs dipeptide protein (DPR) are two proposed mechanisms toxicity C9-ALS/FTLD linked to impaired nucleocytoplasmic transport. Nucleocytoplasmic transport regulated by phenylalanine-glycine nucleoporins (FG nups) that comprise nuclear pore complex (NPC) permeability...
Progressive multifocal leukoencephalopathy (PML)-derived noncoding control region (NCCR) sequences permitted greater early viral gene expression than kidney-associated NCCR sequences. This was driven in part by binding of the transcription factor Spi-B to unique PML-associated sites. is upregulated developing B cells response natalizumab therapy, a known risk for PML. Naturally occurring JCV sequence variation, together with drug treatment-induced cellular changes, may synergize create an...
Abstract The most common genetic cause of amyotrophic lateral sclerosis (ALS) is a GGGGCC (G4C2) hexanucleotide repeat expansions in first intron the C9orf72 gene. accumulation repetitive RNA sequences can mediate toxicity potentially through formation intranuclear foci that sequester key RNA-binding proteins (RBPs), and non-ATG mediated translation into toxic dipeptide protein repeats. However, contribution RBP sequestration to mechanisms underlying RNA-mediated remain unknown. Here we show...
ABSTRACT Amyotrophic lateral sclerosis and frontotemporal dementia patients with a hexanucleotide repeat expansion in C9ORF72 (C9-HRE) accumulate poly-GR poly-PR aggregates. The pathogenicity of these arginine-rich dipeptide repeats (R-DPRs) is thought to be driven by their propensity bind low complexity domains multivalent proteins. However, the ability R-DPRs native RNA significance this interaction remains unclear. We used computational experimental approaches characterize physicochemical...
Abstract Amyotrophic lateral sclerosis (ALS) and Frontotemporal Lobar Degeneration (FTLD) share clinical, neuropathological, genetic features. This includes common disease-causing mutations such as the expanded G4C2 repeat in C9orf72 gene (C9-ALS/FTLD) cytoplasmic insoluble protein depositions of TDP-43 degenerating regions brain spinal cord. Proposed mechanisms toxicity C9-ALS/FTLD are production expansion transcripts their dipeptide proteins (DPRs) products which hypothesized to drive...
Abstract Cellular differentiation occurs through the regulation of lineage-specific gene expression networks that are facilitated by spatial organization genome. Although techniques based on chromatin conformation capture (3C) approach have yielded intrachromosomal genome-wide interaction maps, strategies to identify non-random interchromosomal associations is lacking. Therefore, we modeled genomic chromosomes regulatory involved in pluripotent human embryonic stem cells (hESCs) committed...
SUMMARY The most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) is a hexanucleotide repeat expansion in C9orf72 (C9-HRE). While RNA dipeptide repeats produced by the C9-HRE disrupt nucleocytoplasmic transport, proteins that become redistributed remain unknown. Here, we utilized subcellular fractionation coupled with tandem mass spectrometry identified 126 proteins, enriched for protein translation metabolism pathways, which collectively drive...