Peter EA Ash

Peter EA Ash
Boston University | BU · Department of Pharmacology and Experimental Therapeutics

PhD

About

87
Publications
12,130
Reads
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3,905
Citations
Additional affiliations
August 2007 - March 2013
Mayo Foundation for Medical Education and Research
Position
  • PhD Student
Education
August 2007 - March 2013
Mayo Graduate School, Mayo Clinic College of Medicine
Field of study
  • Molecular Neuroscience
September 2003 - July 2007
The University of Manchester
Field of study
  • Biology with Industrial Experience

Publications

Publications (87)
Article
Full-text available
Frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) are devastating neurodegenerative disorders with clinical, genetic, and neuropathological overlap. Hexanucleotide (GGGGCC) repeat expansions in a noncoding region of C9ORF72 are the major genetic cause of FTD and ALS (c9FTD/ALS). The RNA structure of GGGGCC repeats renders these...
Article
RNA-binding protein TDP-43 has been associated with multiple neurodegenerative diseases, including amyotrophic lateral sclerosis and frontotemporal lobar dementia. We have engineered pan-neuronal expression of human TDP-43 protein in Caenorhabditis elegans, with the goal of generating a convenient in vivo model of TDP-43 function and neurotoxicity....
Article
Graphical abstract Highlights d Tau oligomerization exhibits rapid aggregation of proteins linked to RNA metabolism d Oligomeric tau complexes with HNRNPA2B1 and m 6 A-RNA to regulate RNA translation d Knockdown of HNRNPA2B1 reduces the response to pathological tau d m 6 A progressively increases with disease severity in human AD brains In brief Ol...
Preprint
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We previously identified Hnrnph1 (heterogeneous nuclear ribonucleoprotein H1) as a quantitative trait gene underlying reduced methamphetamine behavioral sensitivity. Mice with a heterozygous frameshift deletion in the first coding exon of Hnrnph1 showed reduced methamphetamine-induced dopamine release and behaviors. To inform the mechanism linking...
Article
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Tau protein plays an important role in the biology of stress granules and in the stress response of neurons, but the nature of these biochemical interactions is not known. Here we show that the interaction of tau with RNA and the RNA binding protein TIA1 is sufficient to drive phase separation of tau at physiological concentrations, without the req...
Preprint
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The microtubule associated protein tau oligomerizes in response to stress and disease, but the function of oligomeric tau (oTau) and the ultimate mechanisms of toxicity are unknown. To gain insights, we have now used Cry2-based optogenetics to induce tau oligomers (oTau-c) in neuronal cultures. oTau-c can seed tau aggregation and biochemical fracti...
Article
Human transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), causative pathogen of the COVID-19 pandemic, exerts a massive health and socioeconomic crisis. The virus infects alveolar epithelial type 2 cells (AT2s), leading to lung injury and impaired gas exchange, but the mechanisms driving infection and pathology are unclear...
Article
We previously identified a 210 kb region on chromosome 11 (50.37-50.58 Mb, mm10) containing two protein-coding genes (Hnrnph1, Rufy1) that was necessary for reduced methamphetamine-induced locomotor activity in C57BL/6J congenic mice harboring DBA/2J polymorphisms. Gene editing of a small deletion in the first coding exon supported Hnrnph1 as a qua...
Preprint
Full-text available
We previously identified a 210 kb region on chromosome 11 (50.37-50.58 Mb, mm10) containing two protein-coding genes (Hnrnph1, Rufy1) that was necessary for reduced methamphetamine-induced locomotor activity in C57BL/6J congenic mice harboring DBA/2J polymorphisms. Gene editing of a deletion in the first coding exon of each gene supported Hnrnph1 a...
Article
Full-text available
Individual variation in the addiction liability of amphetamines has a heritable genetic component. We previously identified Hnrnph1 (heterogeneous nuclear ribonucleoprotein H1) as a quantitative trait gene underlying decreased methamphetamine-induced locomotor activity in mice. Here, we showed that mice (both females and males) with a heterozygous...
Preprint
Full-text available
Individual variation in the addiction liability of amphetamines has a heritable genetic component. We previously identified Hnrnph1 (heterogeneous nuclear ribonucleoprotein H1) as a quantitative trait gene underlying decreased methamphetamine-induced locomotor activity in mice. Here, mice (both male and female) with a heterozygous mutation in the f...
Article
Full-text available
RNA binding proteins (RBPs) are strongly linked to the pathophysiology of motor neuron diseases. Recent studies show that RBPs, such as TIA1, also contribute to the pathophysiology of tauopathy. RBPs co-localize with tau pathology, and reduction of TIA1 protects against tau-mediated neurodegeneration. The mechanism through which TIA1 reduction prot...
Article
Heavy metals, such as lead, mercury and selenium, have been epidemiologically linked with a risk of ALS, but a molecular mechanism proving the connection has not been shown. A screen of putative developmental neurotoxins demonstrated that heavy metals (lead, mercury and tin) trigger accumulation of TDP-43 into nuclear granules with concomitant loss...
Article
Full-text available
The development of insoluble, intracellular neurofibrillary tangles composed of the microtubule-associated protein tau is a defining feature of tauopathies, including Alzheimer’s disease (AD). Accumulating evidence suggests that tau pathology co-localizes with RNA binding proteins (RBPs) that are known markers for stress granules (SGs). Here we use...
Preprint
Full-text available
Highlights • We investigated immunofluorescence and localization of hnRNP H following dopamine receptor activation in primary rat cortical neurons. • Activation of D1 dopamine receptor increased nuclear immunofluorescence of C-terminal but not the N-terminal domain of hnRNP H with no change in either nuclear or cytoplasmic levels of hnRNP H prote...
Article
Full-text available
Emerging studies suggest a role for tau in regulating the biology of RNA binding proteins (RBPs). We now show that reducing the RBP T-cell intracellular antigen 1 (TIA1) in vivo protects against neurodegeneration and prolongs survival in transgenic P301S Tau mice. Biochemical fractionation shows co-enrichment and co-localization of tau oligomers an...
Article
Full-text available
Background Amyotrophic lateral sclerosis (ALS) is a debilitating neurodegenerative condition that is characterized by progressive loss of motor neurons and the accumulation of aggregated TAR DNA Binding Protein-43 (TDP-43, gene: TARDBP). Increasing evidence indicates that environmental factors contribute to the risk of ALS. Dioxins, related planar...
Article
Full-text available
Dendritic mislocalization of microtubule associated protein tau is a hallmark of tauopathies, but the role of dendritic tau is unknown. We now report that tau interacts with the RNA-binding protein (RBP) TIA1 in brain tissue, and we present the brain-protein interactome network for TIA1. Analysis of the TIA1 interactome in brain tissue from wild-ty...
Article
Full-text available
Autophagy is thought to play a pivotal role in the pathophysiology of Parkinson's disease, but little is known about how genes linked to PD affect autophagy in the context of aging. We generated lines of C. elegans expressing reporters for the autophagosome and lysosome expressed only in dopaminergic neurons, and examined autophagy throughout the l...
Article
Full-text available
Caenorhabditis elegans mutants deleted for TDP-1, an ortholog of the neurodegeneration-associated RNA-binding protein TDP-43, display only mild phenotypes. Nevertheless, transcriptome sequencing revealed that many RNAs were altered in accumulation and/or processing in the mutant. Analysis of these transcriptional abnormalities demonstrates that a p...
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Supplementary Table S15
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Source Data for Figure 8
Article
A feature of neurodegenerative disease is the accumulation of insoluble protein aggregates in the brain. In some conditions, including Amyotrophic Lateral Sclerosis and Frontotemporal lobar degeneration, the primary aggregating entities are RNA binding proteins. Through regulated prion-like assembly, RNA binding proteins serve many functions in RNA...
Article
Full-text available
The occurrence of repeat-associated non-ATG (RAN) translation, an atypical form of translation of expanded repeats that results in the synthesis of homopolymeric expansion proteins, is becoming more widely appreciated among microsatellite expansion disorders. Such disorders include amyotrophic lateral sclerosis and frontotemporal dementia caused by...
Article
Full-text available
Frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) are devastating neurodegenerative disorders with clinical, genetic, and neuropathological overlap. A hexanucleotide (GGGGCC) repeat expansion in a non-coding region of C9ORF72 is the major genetic cause of both diseases. The mechanisms by which this repeat expansion causes “c9FTD...
Article
To identify potential genetic modifiers contributing to the phenotypic variability that is detected in patients with repeat expansions in chromosome 9 open reading frame 72 (C9ORF72), we investigated the frequency of these expansions in a cohort of 334 subjects previously found to carry mutations in genes known to be associated with a spectrum of n...
Article
Full-text available
The most common cause of familial frontotemporal lobar degeneration with TAR DNA-binding protein-43 pathology (FTLD-TDP) has been found to be an expansion of a hexanucleotide repeat (GGGGCC) in a noncoding region of the gene C9ORF72. Hippocampal sclerosis (HpScl) is a common finding in FTLD-TDP. Our objective was to screen for the presence of C9ORF...
Data
Characterization of the TDP-1 antibody. Western blotting of protein extracts from wild type N2, tdp-1(ok803) and tdp-1(ok781) strains with a polyclonal anti TDP-1 antibody revealed a signal in N2 worms but no signals from the deletion mutants ok803 or ok781. (TIF)
Data
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Stress assays. Related to Figure 2 and Figure S2. Animals were examined every two hours for survival against the specified stress. (PDF)
Data
tdp-1 is not required for dauer formation or resistance to heat, hypoxia or radiation. (A) tdp-1(ok803) did not interfere with the constitutive dauer-formation phenotype of daf-2(e1370) animals grown at 25°C. (B) tdp-1(ok803) worms were more sensitive to osmotic stress from sorbitol than wild type N2 worms (P<0.001). daf-2(e1370) and daf-2(e1370);t...