A5074739065- RNA regulation and disease
- RNA Research and Splicing
- RNA modifications and cancer
- Cerebrovascular and genetic disorders
- CRISPR and Genetic Engineering
- Pancreatic function and diabetes
- Neuroinflammation and Neurodegeneration Mechanisms
- Neurological Disease Mechanisms and Treatments
- Genetics and Neurodevelopmental Disorders
- Systemic Lupus Erythematosus Research
- Neurological diseases and metabolism
- Endoplasmic Reticulum Stress and Disease
- Pluripotent Stem Cells Research
- Diet, Metabolism, and Disease
- Sleep and Wakefulness Research
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Multiple Sclerosis Research Studies
- Autophagy in Disease and Therapy
- Alzheimer's disease research and treatments
Albert Einstein College of Medicine
2018-2024
Icahn School of Medicine at Mount Sinai
2023
Significance Pathogenic mutations in subunits of RNA polymerase (Pol) III cause a prevalent autosomal recessive form leukodystrophy. However, understanding the mechanisms pathogenesis, including how ubiquitously expressed Pol affect primarily central nervous system, has been limited by absence an animal model disease. We show that conditional knockin pathogenic Polr3a Olig2 lineage mice results growth, neurobehavioral, and hypomyelination phenotypes, reflecting subset clinical features...
Pathogenic variants in subunits of RNA polymerase (Pol) III cause a spectrum Polr3 -related neurodegenerative diseases including 4H leukodystrophy. Disease onset occurs from infancy to early adulthood and is associated with variable range severity neurological non-neurological features. The molecular basis disease pathogenesis unknown. We developed postnatal whole-body mouse model expressing pathogenic Polr3a mutations examine the mechanisms by which reduced Pol transcription results...
Pathogenic variants in subunits of RNA polymerase (Pol) III cause a spectrum Polr3 -related neurodegenerative diseases including 4H leukodystrophy. Disease onset occurs from infancy to early adulthood and is associated with variable range severity neurological non-neurological features. The molecular basis disease pathogenesis unknown. We developed postnatal whole-body mouse model expressing pathogenic Polr3a mutations examine the mechanisms by which reduced Pol transcription results...
During inflammatory, demyelinating diseases such as multiple sclerosis (MS), inflammation and axonal damage are prevalent early in the course. Axonal includes swelling, defects transport, failure to clear damaged intracellular proteins, all of which affect recovery compromise neuronal integrity. The clearance cell components is important maintain normal turnover restore homeostasis. In this study, we used mass spectrometry identify insoluble proteins within...
Pathogenic variants in subunits of RNA polymerase (Pol) III cause a spectrum neurodegenerative diseases including 4H leukodystrophy. Disease onset occurs from infancy to early adulthood and is associated with variable range severity neurological non-neurological features. The molecular basis disease pathogenesis unknown. We developed postnatal whole-body mouse model expressing pathogenic Polr3a mutations examine the mechanisms by which reduced Pol transcription results primarily central...
Pathogenic variants in subunits of RNA polymerase (Pol) III cause a spectrum Polr3 -related neurodegenerative diseases including 4H leukodystrophy. Disease onset occurs from infancy to early adulthood and is associated with variable range severity neurological non-neurological features. The molecular basis disease pathogenesis unknown. We developed postnatal whole-body mouse model expressing pathogenic Polr3a mutations examine the mechanisms by which reduced Pol transcription results...
Abstract RNA polymerase (Pol) III synthesizes abundant short non-coding RNAs that have essential functions in protein synthesis, secretion and other processes. Despite the ubiquitous of these RNAs, mutations Pol subunits cause III-related leukodystrophy, an early-onset neurodegenerative disease. The basis this neural sensitivity mechanisms disease pathogenesis are unknown. Here we show mice expressing pathogenic largest subunit, Polr3a , specifically Olig2-expressing cells, impaired growth...
Successful genome editing in primary human islets could reveal features of the genetic regulatory landscape underlying β cell function and diabetes risk. Here, we describe a CRISPR-based strategy to interrogate functions predicted DNA elements using electroporation complex Cas9 ribonucleoprotein (Cas9 RNP) guide RNAs into islet cells. We successfully targeted coding regions including
Summary Successful genome editing in primary human islets could reveal features of the genetic regulatory landscape underlying β cell function and diabetes risk. Here, we describe a CRISPR-based strategy to interrogate functions predicted DNA elements using electroporation complex Cas9 ribonucleoprotein (Cas9 RNP) guide RNAs into islet cells. We successfully targeted coding regions including PDX1 exon 1, non-coding linked susceptibility. CRISPR/Cas9 RNP approaches revealed targets regulation...
Pathogenic variants in subunits of RNA polymerase (Pol) III cause a spectrum