A5026639772- Amyotrophic Lateral Sclerosis Research
- Neurogenetic and Muscular Disorders Research
- RNA Research and Splicing
- Parkinson's Disease Mechanisms and Treatments
- Genetic Neurodegenerative Diseases
- Pneumocystis jirovecii pneumonia detection and treatment
- Genetic and Kidney Cyst Diseases
- Fibroblast Growth Factor Research
- Neurological diseases and metabolism
- Renal and related cancers
- Wnt/β-catenin signaling in development and cancer
- Prion Diseases and Protein Misfolding
- Peptidase Inhibition and Analysis
- Protease and Inhibitor Mechanisms
- Organ Donation and Transplantation
- Cancer-related gene regulation
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
MaineGeneral Medical Center
2024
Harvard University
2020-2024
Massachusetts General Hospital
2020-2024
Broad Institute
2020-2022
Association pour la Recherche de Thérapeutiques Innovantes en Cancérologie
2022
University of Zurich
2022
University of California, San Francisco
2016
National Tsing Hua University
1999
Abstract Nuclear clearance and cytoplasmic accumulations of the RNA-binding protein TDP-43 are pathological hallmarks in almost all patients with amyotrophic lateral sclerosis (ALS) up to 50% frontotemporal dementia (FTD) Alzheimer’s disease. In disease, pathology is predominantly observed limbic system correlates cognitive decline reduced hippocampal volume. Disruption nuclear function leads abnormal RNA splicing incorporation erroneous cryptic exons numerous transcripts including...
Most current microfluidic cell culture systems are integrated single use devices. This can limit throughput and experimental design options, particularly for epithelial cells, which require significant time in to obtain a fully differentiated phenotype. In addition, cells porous growth substrate order polarize their distinct apical basolateral membranes. We have developed modular system using commercially available inserts evaluate polarized under physiologically relevant fluid flow...
Abstract Mutations in FUS, an RNA-binding protein involved multiple steps of RNA metabolism, are associated with the most severe forms amyotrophic lateral sclerosis (ALS). Accumulation cytoplasmic FUS is likely to be a major culprit toxicity mutations. Thus, preventing mislocalization may represent valuable therapeutic strategy. binds its own pre-mRNA creating autoregulatory loop efficiently buffering excess through proposed mechanisms including retention introns 6 and/or 7. Here, we...
ABSTRACT Amino acid residues in the metal-binding and putative substrate-binding sites of Escherichia coli methionine aminopeptidase (MAP) were mutated, their effects on function enzyme investigated. Substitution any amino residue at site resulted complete loss two cobalt ions bound to protein diminished activity. However, only Cys70 Trp221 are involved catalytic activity MAP. Changing either them caused partial activity, while mutations both positions abolished MAP function. Both found be...
Hexanucleotide G 4 C 2 repeat expansions in the C9orf72 gene are most common genetic cause of amyotrophic lateral sclerosis and frontotemporal dementia. Dipeptide proteins (DPRs) generated by translation repeat-containing RNAs show toxic effects vivo as well vitro key targets for therapeutic intervention. We human antibodies that bind DPRs with high affinity specificity. Anti-GA engaged extra- intra-cellular poly-GA reduced aggregate formation a overexpressing cell line. However, antibody...
Although mutations in dozens of genes have been implicated familial forms amyotrophic lateral sclerosis (fALS) and frontotemporal degeneration (fFTD), most cases these conditions are sporadic (sALS sFTD), with no family history, their etiology remains obscure. We tested the hypothesis that somatic mosaic mutations, present some but not all cells, might contribute cases, by performing ultra-deep, targeted sequencing 88 associated neurodegenerative diseases postmortem brain spinal cord samples...
Abstract Mutations in FUS, an RNA-binding protein involved multiple steps of RNA metabolism, are associated with the most severe forms amyotrophic lateral sclerosis (ALS). Accumulation cytoplasmic FUS is likely to be a major culprit toxicity mutations. Thus, preventing mislocalization may represent valuable therapeutic strategy. binds its own pre-mRNA creating autoregulatory loop efficiently buffering excess through proposed mechanisms including retention introns 6 and/or 7. Here, we...
Abstract Hexanucleotide G 4 C 2 repeat expansions in the C9ORF72 gene are most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Dipeptide proteins (DPRs) generated by translation repeat-containing RNAs show toxic effects vivo as well vitro key targets for therapeutic intervention. We human antibodies that bind DPRs with high affinity specificity. Anti-GA engaged extra- intracellular poly-GA reduced aggregate formation a over-expressing cell line....