A5090826799- RNA and protein synthesis mechanisms
- Genomics and Chromatin Dynamics
- RNA Research and Splicing
- Genetics and Neurodevelopmental Disorders
- Tryptophan and brain disorders
- Chromatin Remodeling and Cancer
- Single-cell and spatial transcriptomics
- Neurogenesis and neuroplasticity mechanisms
- Neuroinflammation and Neurodegeneration Mechanisms
- CRISPR and Genetic Engineering
- MicroRNA in disease regulation
- RNA modifications and cancer
- Fungal and yeast genetics research
- Genomics and Rare Diseases
- Bioinformatics and Genomic Networks
- SARS-CoV-2 detection and testing
- Advanced biosensing and bioanalysis techniques
- Genetic Associations and Epidemiology
- Cell Image Analysis Techniques
- Gut microbiota and health
- Genetic Neurodegenerative Diseases
University of California, San Francisco
2022-2024
Rutgers, The State University of New Jersey
2020-2023
Johnson University
2020-2023
University of Oxford
2023
University of California, Los Angeles
2020
Center for Autism and Related Disorders
2020
McGill University
2001
In Saccharomyces cerevisiae , more than 80% of the ∼6200 predicted genes are nonessential, implying that genome is buffered from phenotypic consequences genetic perturbation. To evaluate function, we developed a method for systematic construction double mutants, termed synthetic array (SGA) analysis, in which query mutation crossed to an ∼4700 deletion mutants. Inviable double-mutant meiotic progeny identify functional relationships between genes. SGA analysis with roles cytoskeletal...
Many autism spectrum disorder (ASD)-associated genes act as transcriptional regulators (TRs). Chromatin immunoprecipitation sequencing (ChIP-seq) was used to identify the regulatory targets of ARID1B, BCL11A, FOXP1, TBR1, and TCF7L2, ASD-associated TRs in developing human mouse cortex. These shared substantial overlap binding sites, especially within open chromatin. The a promoter region, 1–2,000 bp upstream transcription start site, highly predictive brain-expressed genes. This signature...
Neurodevelopment requires precise regulation of gene expression, including post-transcriptional regulatory events such as alternative splicing and mRNA translation. However, translational specific isoforms during neurodevelopment the mechanisms behind it remain unknown. Using RNA-seq analysis mouse neocortical polysomes, here we report translationally repressed derepressed neurogenesis whose orthologs include risk genes for neurodevelopmental disorders. We demonstrate that translation...
Abstract Abnormalities in neocortical and synaptic development are linked to neurodevelopmental disorders. However, the molecular cellular mechanisms governing initial synapse formation prenatal neocortex remain poorly understood. Using polysome profiling coupled with snRNAseq on human cortical samples at various fetal phases, we identify mRNAs, including those encoding proteins, finely controlled translation distinct cell populations of developing frontal neocortices. Examination murine...
CRISPR-based gene activation (CRISPRa) is a promising therapeutic approach for therapy, upregulating expression by targeting promoters or enhancers in tissue/cell-type specific manner. Here, we describe an experimental framework that combines highly multiplexed perturbations with single-cell RNA sequencing (sc-RNA-seq) to identify cell-type-specific, CRISPRa-responsive
Genetic studies find hundreds of thousands noncoding variants associated with psychiatric disorders. Massively parallel reporter assays (MPRAs) and
Missense variants that alter a single amino acid in the encoded protein contribute to many human disorders but pose substantial challenge interpretation. Though these can be reliably identified through sequencing, distinguishing clinically significant ones remains difficult, such "Variants of Unknown Significance" outnumber those classified as "Pathogenic" or "Likely Pathogenic." Numerous
Abstract Background Maternal immune activation (MIA) is a proposed risk factor for multiple neurodevelopmental and psychiatric disorders, including schizophrenia. However, the molecular neurobiological mechanisms through which MIA imparts these disorders remain poorly understood. A recently developed nonhuman primate model of exposure to viral mimic poly:ICLC during pregnancy shows abnormal social repetitive behaviors elevated striatal dopamine, hallmark human psychosis, providing an...
Abstract Many autism spectrum disorder (ASD)-associated genes act as transcriptional regulators (TRs). ChIP-seq was used to identify the regulatory targets of ARID1B, BCL11A, FOXP1, TBR1, and TCF7L2, ASD-associated TRs in developing human mouse cortex. These shared substantial overlap binding sites, especially within open chromatin. The a promoter region, 1-2,000bp upstream transcription start site, highly predictive brain expressed genes. This signature observed at 96 out 102 In vitro...