A5089710780- RNA Research and Splicing
- Amyotrophic Lateral Sclerosis Research
- Neurogenetic and Muscular Disorders Research
- Nuclear Structure and Function
- RNA and protein synthesis mechanisms
- RNA modifications and cancer
- RNA regulation and disease
- Viral Infections and Immunology Research
- Neurological diseases and metabolism
- Prion Diseases and Protein Misfolding
- Neuroinflammation and Neurodegeneration Mechanisms
- Hybrid Renewable Energy Systems
- Muscle Physiology and Disorders
- S100 Proteins and Annexins
- Endoplasmic Reticulum Stress and Disease
- Histone Deacetylase Inhibitors Research
- RNA Interference and Gene Delivery
- Peptidase Inhibition and Analysis
- Cell Adhesion Molecules Research
University of Pennsylvania
2018-2025
Johns Hopkins University
2023-2024
Johns Hopkins Medicine
2024
Institute of Molecular Biology and Biophysics
2021
Nuclear import receptors, also called importins, mediate nuclear of proteins and chaperone aggregation-prone cargoes (e.g., neurodegeneration-linked RNA-binding [RBPs]) in the cytoplasm. Importins were identified as modulators cellular toxicity elicited by arginine-rich dipeptide repeat (DPRs), an aberrant protein species found C9orf72-linked amyotrophic lateral sclerosis (ALS) frontotemporal dementia (FTD). Mechanistically, link between importins DPRs remains unclear. Here, we show that...
The separation of genetic material from bulk cytoplasm has enabled the evolution increasingly complex organisms, allowing for development sophisticated forms life. However, this complexity created new categories dysfunction, including those related to movement between cellular compartments. In eukaryotic cells, nucleocytoplasmic trafficking is a fundamental biological process, and cumulative disruptions nuclear integrity transport are detrimental cell survival. This particularly true in...
Mutations in HNRNPA1 encoding heterogeneous nuclear ribonucleoprotein (hnRNP) A1 are a rare cause of amyotrophic lateral sclerosis (ALS) and multisystem proteinopathy (MSP). hnRNPA1 is part the group RNA-binding proteins (RBPs) that assemble with RNA to form RNPs. hnRNPs concentrated nucleus function pre-mRNA splicing, mRNA stability, regulation transcription translation. During stress, hnRNPs, mRNA, other RBPs condense cytoplasm stress granules (SGs). SGs implicated pathogenesis...
Missense variants in RNA-binding proteins (RBPs) underlie a spectrum of disease phenotypes, including amyotrophic lateral sclerosis, frontotemporal dementia, and inclusion body myopathy. Here, we present ten independent families with severe, progressive muscular dystrophy, reminiscent oculopharyngeal dystrophy (OPMD) but much earlier onset, caused by heterozygous frameshift the RBP hnRNPA2/B1. All disease-causing mutations abolish native stop codon extend reading frame, creating novel...
TMEM106B is a lysosomal/late endosome protein that potent genetic modifier of multiple neurodegenerative diseases as well general aging. Recently, was shown to form insoluble aggregates in postmortem human brain tissue, drawing attention pathology and the potential role aggregation disease. In context diseases, has been studied
TMEM106B is a lysosomal/late endosome protein that potent genetic modifier of multiple neurodegenerative diseases as well general aging. Recently, was shown to form insoluble aggregates in postmortem human brain tissue, drawing attention pathology and the potential role aggregation disease. In context diseases, has been studied
Summary RNA-binding proteins (RBPs) are essential for post-transcriptional regulation and processing of RNAs. Pathogenic missense variants in RBPs underlie a spectrum disease phenotypes, including amyotrophic lateral sclerosis, frontotemporal dementia, inclusion body myopathy, distal Paget’s the bone. Here, we present ten independent families with severe, progressive, early-onset muscular dystrophy, reminiscent oculopharyngeal dystrophy (OPMD), caused by heterozygous frameshift prion-like...
Poly(ADP-ribose) (PAR) is an RNA-like polymer that regulates increasing number of biological processes. Dysregulation PAR implicated in neurodegenerative diseases characterized by abnormal protein aggregation, including Amyotrophic Lateral Sclerosis (ALS). forms condensates with FUS, RNA-binding linked ALS, through unknown mechanism. Here, we demonstrate a strikingly low concentration (1 nM) sufficient to trigger condensation FUS near its physiological µM), which three orders magnitude lower...