A5080351243- Autism Spectrum Disorder Research
- Genetics and Neurodevelopmental Disorders
- Dementia and Cognitive Impairment Research
- Genetic Associations and Epidemiology
- Alzheimer's disease research and treatments
- RNA Research and Splicing
- RNA modifications and cancer
- Genetics, Bioinformatics, and Biomedical Research
- Bioinformatics and Genomic Networks
- Genomic variations and chromosomal abnormalities
- RNA regulation and disease
- Genomics and Chromatin Dynamics
- Advanced Neuroimaging Techniques and Applications
- Medical Image Segmentation Techniques
- Genomics and Rare Diseases
- Epigenetics and DNA Methylation
- Gene expression and cancer classification
- Acute Myeloid Leukemia Research
- Single-cell and spatial transcriptomics
- Neuroinflammation and Neurodegeneration Mechanisms
- Neurogenesis and neuroplasticity mechanisms
- RNA and protein synthesis mechanisms
- Neurological Disease Mechanisms and Treatments
- Congenital heart defects research
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
Regeneron (United States)
2022-2025
University of California, San Francisco
2019-2023
Broad Center
2022-2023
Center for Autism and Related Disorders
2013-2022
University of California, Los Angeles
2009-2020
UCLA Health
2008-2013
Max Planck Research Unit for Neurogenetics
2012
Cognitive Neuroimaging Lab
2008
Genes overlap across psychiatric disease Many genome-wide studies have examined genes associated with a range of neuropsychiatric disorders. However, the degree to which genetic underpinnings these diseases differ or is unknown. Gandal et al. performed meta-analyses transcriptomic covering five major disorders and compared cases controls identify coexpressed gene modules. From this, they found that some share global expression patterns. This in polygenic traits may allow for better diagnosis...
Abstract Obesity is associated with increased risk for cardiovascular health problems including diabetes, hypertension, and stroke. These afflictions increase cognitive decline dementia, but it unknown whether these factors, specifically obesity Type II are specific patterns of brain atrophy. We used tensor‐based morphometry (TBM) to examine gray matter (GM) white (WM) volume differences in 94 elderly subjects who remained cognitively normal at least 5 years after their scan. Bivariate...
The association of histone modification changes with autism spectrum disorder (ASD) has not been systematically examined. We conducted a acetylome-wide study (HAWAS) by performing H3K27ac chromatin immunoprecipitation sequencing (ChIP-seq) on 257 postmortem samples from ASD and matched control brains. Despite etiological heterogeneity, ≥68% syndromic idiopathic cases shared common acetylome signature at >5,000 cis-regulatory elements in prefrontal temporal cortex. Similarly, multiple genes...
Abstract Autism spectrum disorder (ASD) is more prevalent in males, and the mechanisms behind this sex-differential risk are not fully understood. Two competing, but mutually exclusive, hypotheses that ASD genes sex-differentially regulated, or alternatively, they interact with characteristic sexually dimorphic pathways. Here we characterized gene expression multiple data sets from neurotypical adult prenatal human neocortical tissue, evaluated for evidence of sex-biased expression. We find...
The predisposition to neuropsychiatric disease involves a complex, polygenic, and pleiotropic genetic architecture. However, little is known about how variants impart brain dysfunction or pathology. We used transcriptomic profiling as quantitative readout of molecular brain-based phenotypes across five major psychiatric disorders—autism, schizophrenia, bipolar disorder, depression, alcoholism—compared with matched controls. identified patterns shared distinct gene-expression perturbations...
Abstract Neuropsychiatric disorders classically lack defining brain pathologies, but recent work has demonstrated dysregulation at the molecular level, characterized by transcriptomic and epigenetic alterations 1–3 . In autism spectrum disorder (ASD), this pathology involves upregulation of microglial, astrocyte neural–immune genes, downregulation synaptic attenuation gene-expression gradients in cortex 1,2,4–6 However, whether these changes are limited to cortical association regions or...
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...
RNA splicing plays a critical role in the programming of neuronal differentiation and, consequently, normal human neurodevelopment, and its disruption may underlie neurodevelopmental neuropsychiatric disorders. The RNA-binding protein, fox-1 homolog (RBFOX1; also termed A2BP1 or FOX1), is neuron-specific factor predicted to regulate networks clinically implicated disease, including autism spectrum disorder (ASD), but only few targets have been experimentally identified. We used sequencing...
Abstract We used a new method we developed for automated hippocampal segmentation, called the auto context model, to analyze brain MRI scans of 400 subjects from Alzheimer's disease neuroimaging initiative. After training classifier on 21 hand‐labeled expert segmentations, created binary maps hippocampus three age‐ and sex‐matched groups: 100 with (AD), 200 mild cognitive impairment (MCI) elderly controls (mean age: 75.84; SD: 6.64). Hippocampal traces were converted parametric surface...