A5061711255- DNA Repair Mechanisms
- Neuroinflammation and Neurodegeneration Mechanisms
- Cell Image Analysis Techniques
- Single-cell and spatial transcriptomics
- CRISPR and Genetic Engineering
- DNA and Nucleic Acid Chemistry
- Enzyme Structure and Function
- Virus-based gene therapy research
- Amyotrophic Lateral Sclerosis Research
- Neurogenesis and neuroplasticity mechanisms
- RNA and protein synthesis mechanisms
- Virology and Viral Diseases
- Bacteriophages and microbial interactions
- Bacterial Genetics and Biotechnology
- Food Allergy and Anaphylaxis Research
- Biochemical and Molecular Research
- Neurological diseases and metabolism
- RNA regulation and disease
- PARP inhibition in cancer therapy
- Advanced Fluorescence Microscopy Techniques
- Parkinson's Disease Mechanisms and Treatments
- HIV Research and Treatment
- Mitochondrial Function and Pathology
- Alzheimer's disease research and treatments
- RNA Interference and Gene Delivery
University of California, San Francisco
2019-2024
Broad Center
2020-2024
DRG Undersea Consulting (United States)
2024
Neurological Surgery
2022-2024
Lawrence Berkeley National Laboratory
2010-2022
Washington University in St. Louis
2022
Massachusetts General Hospital
2016-2018
Harvard University
2016-2018
Joint BioEnergy Institute
2017
Scripps Research Institute
2000-2015
Abstract During mammalian development, differences in chromatin state coincide with cellular differentiation and reflect changes the gene regulatory landscape 1 . In developing brain, cell fate specification topographic identity are important for defining 2 confer selective vulnerabilities to neurodevelopmental disorders 3 Here, identify cell-type-specific accessibility patterns human we used a single-cell assay transposase by sequencing (scATAC-seq) primary tissue samples from forebrain. We...
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) readily infects a variety of cell types impacting the function vital organ systems, with particularly impact on function. Neurological symptoms, which range in severity, accompany as many one-third COVID-19 cases, indicating potential vulnerability neural types. To assess whether human cortical cells can be directly infected by SARS-CoV-2, we utilized stem-cell-derived organoids well primary tissue, both from developmental and...
Adeno-associated viruses (AAVs) hold tremendous promise as delivery vectors for gene therapies. AAVs have been successfully engineered—for instance, more efficient and/or cell-specific to numerous tissues—by creating large, diverse starting libraries and selecting desired properties. However, these often contain a high proportion of variants unable assemble or package their genomes, prerequisite any goal. Here, we present showcase machine learning (ML) method designing AAV peptide insertion...
Peanut allergy is a significant health problem because of the prevelance and potential severity allergic reaction. Serum IgE from patients with documented peanut hypersensitivity reactions overlapping peptides were used to identify IgE‐binding epitopes on major allergen, Ara h 1. At least twenty‐three different linear epitopes, located throughout length 1 protein, identified. All 6–10 amino acids in length, but there was no obvious sequence motif shared by all peptides. Four appeared be...
Abstract In the past decade, there has been an increase in allergic reactions to peanut proteins, sometimes resulting fatal anaphylaxis. The development of improved methods for diagnosis and treatment allergies requires a better understanding structure allergens. Ara h 1, major allergen belonging vicilin family seed storage is recognized by serum IgE from >90% peanut-allergic patients. this communication, 1 was shown form highly stable homotrimer. Hydrophobic interactions were...
Allergy to peanut is a significant IgE-mediated health problem because of the high prevalence, potential severity, and chronicity reaction. Ara h1, an abundant protein, recognized by serum IgE from >90% peanut-sensitive individuals. It has been shown belong vicilin family seed storage proteins contain 23 linear binding epitopes. In this communication, we have determined critical amino acids within each epitopes h1 that are important for immunoglobulin binding. Surprisingly, substitution...
Significance The genetic basis of X-Linked dystonia-parkinsonism (XDP) has been difficult to unravel, in part because all patients inherit the same haplotype seven sequence variants, none which ever identified control individuals. This study revealed that one markers, a retrotransposon insertion within an intron TAF1 , variable number hexameric repeats among affected individuals with increase repeat strongly correlated earlier age at disease onset. These data support contributing role for...
We report quantitative label-free imaging with phase and polarization (QLIPP) for simultaneous measurement of density, anisotropy, orientation structures in unlabeled live cells tissue slices. combine QLIPP deep neural networks to predict fluorescence images diverse cell structures. reveal anatomical regions axon tract prenatal human brain sections that are not visible using brightfield imaging. a variant U-Net architecture, multi-channel 2.5D U-Net, computationally efficient prediction...
Progenitors of the developing human neocortex reside in ventricular and outer subventricular zones (VZ OSVZ, respectively). However, whether cells derived from these niches have similar developmental fates is unknown. By performing fate mapping primary tissue, we demonstrate that astrocytes populate anatomically distinct layers. Cortical plate emerge VZ progenitors proliferate locally, while putative white matter are morphologically heterogeneous both OSVZ progenitors. Furthermore, via...
The thalamus plays a central coordinating role in the brain. Thalamic neurons are organized into spatially distinct nuclei, but molecular architecture of thalamic development is poorly understood, especially humans. To begin to delineate trajectories cell fate specification and organization developing human thalamus, we used single-cell multiplexed spatial transcriptomics. We show that molecularly defined differentiate second trimester these organize nuclei. identified major subtypes...
Significance Mutations in human Cu, Zn superoxide dismutase (SOD) cause the motor neuron disease ALS. To better understand why, we compared aggregation, metal binding, and conformational dynamics of normal mutant SOD proteins by using biophysical techniques X-ray scattering, inductively coupled plasma MS, ESR spectroscopy. For with defects at a mutational hotspot, found that copper deficiency, flexibility, aggregation paralleled clinical severity ALS patients. These data support unifying...
ABSTRACT The processing of DNA double-strand breaks is a critical event in nucleic acid metabolism. This evidenced by the severity phenotypes associated with deficiencies this process multiple organisms. core component involved break repair eukaryotic cells Mre11-Rad50 protein complex, which includes third protein, p95, humans and Xrs2 yeasts. Homologues Mre11 Rad50 have been identified all kingdoms life, while Nbs1 family found only eukaryotes. In eukaryotes complex has nuclease activity...