A5091008247- Amyotrophic Lateral Sclerosis Research
- Neurogenetic and Muscular Disorders Research
- RNA Research and Splicing
- Cell Image Analysis Techniques
- Cancer Cells and Metastasis
- Neuroscience and Neuropharmacology Research
- Cancer-related gene regulation
- Neurogenesis and neuroplasticity mechanisms
- Retinal Development and Disorders
- Cellular Mechanics and Interactions
- Prion Diseases and Protein Misfolding
- Mitochondrial Function and Pathology
- Pluripotent Stem Cells Research
- MicroRNA in disease regulation
- Genetic Neurodegenerative Diseases
- Neuroscience and Neural Engineering
- Skin and Cellular Biology Research
- Epigenetics and DNA Methylation
- Image Processing Techniques and Applications
- Spectroscopy Techniques in Biomedical and Chemical Research
- Silk-based biomaterials and applications
- CRISPR and Genetic Engineering
- RNA modifications and cancer
- Microbial Inactivation Methods
- Histone Deacetylase Inhibitors Research
Gladstone Institutes
2016-2025
Taube Koret Center
2016-2021
University of California, San Francisco
2009-2014
Translational Genomics Research Institute
2013
Broad Center
2009
Cold Spring Harbor Laboratory
2001-2005
Stony Brook University
2001-2005
Stony Brook School
1998-2003
State University of New York
2001
There has been a growing interest in using next-generation sequencing (NGS) to profile extracellular small RNAs from the blood and cerebrospinal fluid (CSF) of patients with neurological diseases, CNS tumors, or traumatic brain injury for biomarker discovery. Small sample volumes samples low RNA abundance create challenges downstream assays. Plasma, serum, CSF contain amounts total RNA, which make up fraction. The purpose this study was maximize isolation RNA-limited apply these methods...
The excitatory neurons of the mammalian cerebral cortex arise from asymmetric divisions radial glial cells in ventricular zone and symmetric division intermediate progenitor (IPCs) subventricular (SVZ) embryonic cortex. Little is known about microenvironment which IPCs divide or whether a stem cell niche exists SVZ Recent evidence suggests that vasculature may provide for adult but its role development less clear. We have investigated during neurogenesis find are spatially temporally...
Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disorder typically characterized by insoluble inclusions of hyperphosphorylated TDP-43. The mechanisms underlying toxic TDP-43 accumulation are not understood. Persistent activation p38 mitogen-activated protein kinase (MAPK) implicated in ALS. However, it unclear how MAPK affects proteinopathy. Here, we show that p38α inhibition reduces pathological phosphorylation, aggregation, cytoplasmic mislocalization, and...
Abstract Current approaches for dynamic profiling of single cells rely on dissociated cultures, which lack important biological features existing in tissues. Organotypic slice cultures preserve aspects structural and synaptic organisation within the brain are amenable to microscopy, but established techniques not well adapted high throughput or longitudinal cell analysis. Here we developed a custom-built, automated confocal imaging platform, with improved organotypic culture maintenance. The...
Abstract Cell death is a critical process that occurs normally in health and disease. However, its study limited due to available technologies only detect very late stages the or specific mechanisms. Here, we report development of family fluorescent biosensors called genetically encoded indicators (GEDIs). GEDIs specifically an intracellular Ca 2+ level cells achieve early cell marks stage at which are irreversibly committed die. The time-resolved nature GEDI delineates binary demarcation...
Persistent cytoplasmic aggregates containing RNA binding proteins (RBPs) are central to the pathogenesis of late-onset neurodegenerative disorders such as amyotrophic lateral sclerosis (ALS). These share components, molecular mechanisms, and cellular protein quality control pathways with stress-induced granules (SGs). Here, we assess impact stress on global mRNA localization landscape human pluripotent stem cell-derived motor neurons (PSC-MNs) using subcellular fractionation sequencing...
Abstract Mechanisms controlling dendritic arbor formation affect the establishment of neuronal circuits. Candidate plasticity gene 15 (CPG15) is a glycosylphosphatidyl inositol (GPI)‐linked activity‐induced protein that has been shown to function as an intercellular signaling molecule can promote morphological and physiological development Xenopus retinotectal system. A thorough understanding CPG15 requires knowledge spatiotemporal expression endogenous protein. We therefore cloned cpg15...
High-throughput microscopy has outpaced analysis; biomarker-optimized CNNs are a generalizable, fast, and interpretable solution.
Abstract Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder typically characterized by insoluble inclusions of hyperphosphorylated TDP-43. The mechanisms underlying toxic TDP-43 accumulation are not understood. Persistent activation p38 mitogen-activated protein kinase (MAPK) implicated in ALS. However, it unclear how MAPK affects proteinopathy. Here, we demonstrate that inhibition p38α reduces pathological phosphorylation, aggregation, cytoplasmic mislocalization, and...
Re-epithelialization is defined as the reconstitution of cells into an organized, stratified squamous epithelium that permanently covers a wound defect and restores function (). Following wounding, keratinocytes are activated to undergo series phenotypic changes have been well-characterized in vivo (, , ). However, vitro studies re-epithelialization often limited by their inability simulate tissue. Wound models using skin explants ) or submerged keratinocyte cultures (,) demonstrate only...
Abstract Cell death is a critical process that occurs normally in health and disease. However, its study limited due to available technologies only detect very late stages the or specific mechanisms. Here, we report development of new fluorescent biosensor called genetically encoded indicator (GEDI). GEDI specifically detects an intracellular Ca 2+ level cells achieve early cell marks stage at which are irreversibly committed die. The time-resolved nature delineates binary demarcation life...
Abstract Cell death is an essential process in biology that must be accounted for live microscopy experiments. Nevertheless, cell difficult to detect without perturbing experiments with stains, dyes or biosensors can bias experimental outcomes, lead inconsistent results, and reduce the number of processes simultaneously labelled. These additional steps also make scale high-throughput screening because cost, labor, analysis they entail. We address this fundamental limitation...