A5074244879- Amyotrophic Lateral Sclerosis Research
- RNA and protein synthesis mechanisms
- CRISPR and Genetic Engineering
- Genetic Neurodegenerative Diseases
- Mitochondrial Function and Pathology
- Cell Image Analysis Techniques
- RNA Research and Splicing
- Diet and metabolism studies
- Diabetes, Cardiovascular Risks, and Lipoproteins
- Epigenetics and DNA Methylation
- Autism Spectrum Disorder Research
- Genetics and Neurodevelopmental Disorders
- Single-cell and spatial transcriptomics
- Peroxisome Proliferator-Activated Receptors
- Gene Regulatory Network Analysis
- Alzheimer's disease research and treatments
Washington University in St. Louis
2024
National Institute of Neurological Disorders and Stroke
2019
National Institutes of Health
2019
Georgetown University
2016
Long-distance RNA transport enables local protein synthesis at metabolically-active sites distant from the nucleus. This process ensures an appropriate spatial organization of proteins, vital to polarized cells such as neurons. Here, we present a mechanism for in which granules "hitchhike" on moving lysosomes. In vitro biophysical modeling, live-cell microscopy, and unbiased proximity labeling proteomics reveal that annexin A11 (ANXA11), granule-associated phosphoinositide-binding protein,...
Highlights•A CRISPR interference platform for genetic screens in human iPSC-derived neurons•Survival uncover genes essential neurons, but not iPSCs or cancer cells•Single-cell RNA-seq reveal distinct neuronal roles ubiquitous genes•Arrayed high-content controlling morphologySummaryCRISPR/Cas9-based functional genomics have transformed our ability to elucidate mammalian cell biology. However, most previous CRISPR-based were conducted lines rather than healthy, differentiated cells. Here, we...
How dipeptide repeats cause pathology A repeat expansion in the chromosome 9 open reading frame 72 ( C9orf72 ) gene is most common known of two neurodegenerative diseases: frontotemporal dementia and amyotrophic lateral sclerosis. This leads to abnormal production proteins repeating dipeptides, but their contribution disease pathogenesis remains unclear. Zhang et al. engineered a mouse model study consequences one these dipeptides—prolinearginine protein, poly(PR)—in brain. They found that...
Apolipoprotein E (apoE) is associated with lipoproteins in the cerebrospinal fluid (CSF). APOE4 increases and APOE2 decreases risk for Alzheimer disease (AD) compared to APOE3 Because apoE4 less efficient at cholesterol efflux than apoE2 or apoE3 vitro, we hypothesized that APOE genotype may affect apoE particle size vivo these differences be related AD risk. We used nondenaturing gel electrophoresis test of complexes human CSF samples various genotypes created profiles each sample compare...
Wide variation of responses to identical stimuli presented genetically inbred mice suggests the hypothesis that stochastic epigenetic during neurodevelopment can mediate such phenotypic differences. However , this is largely untested since capturing pre-existing molecular states requires non-destructive, longitudinal recording. Therefore, we tested potential Calling Cards (CC) record transient neuronal enhancer activity postnatal development, and thereby associate with a subsequent...
SUMMARY CRISPR/Cas9-based functional genomics have transformed our ability to elucidate mammalian cell biology. However, most previous CRISPR-based screens were conducted in cancer lines, rather than healthy, differentiated cells. Here, we describe a CRISPR interference (CRISPRi)-based platform for genetic human neurons derived from induced pluripotent stem cells (iPSCs). We demonstrate robust and durable knockdown of endogenous genes such neurons, present results three complementary...