Changuk Chung
A5075986960- Genetics and Neurodevelopmental Disorders
- Autism Spectrum Disorder Research
- Genomic variations and chromosomal abnormalities
- Neuroscience and Neuropharmacology Research
- Genomics and Rare Diseases
- Single-cell and spatial transcriptomics
- Cancer Genomics and Diagnostics
- Epigenetics and DNA Methylation
- Neurogenesis and neuroplasticity mechanisms
- Neural dynamics and brain function
- Genomics and Chromatin Dynamics
- Neuroendocrine regulation and behavior
- RNA Research and Splicing
- Fetal and Pediatric Neurological Disorders
- Cell Image Analysis Techniques
- Renal and related cancers
- Trace Elements in Health
- Cancer Cells and Metastasis
- Genomics and Phylogenetic Studies
- Wnt/β-catenin signaling in development and cancer
- Ion channel regulation and function
- Developmental Biology and Gene Regulation
- Genetic Associations and Epidemiology
- Connective tissue disorders research
- CRISPR and Genetic Engineering
University of California, San Diego
2020-2025
Children’s Institute
2020-2025
Institute for Basic Science
2015-2021
Korea Advanced Institute of Science and Technology
2012-2018
Creative Research
2012
Ajou University
2004
Shank3 is a postsynaptic scaffolding protein implicated in synapse development and autism spectrum disorders. The gene known to produce diverse splice variants whose functions have not been fully explored. In the present study, we generated mice lacking exon 9 (Shank3 (Δ9) mice), thus missing five out of 10 containing N-terminal ankyrin repeat region, including longest variant, Shank3a. Our X-gal staining results revealed that proteins encoded by 9-containing are abundant upper cortical...
Abstract Genetic aspects of autism spectrum disorders (ASDs) have recently been extensively explored, but environmental influences that affect ASDs received considerably less attention. Zinc (Zn) is a nutritional factor implicated in ASDs, evidence for strong association and linking mechanism largely lacking. Here we report trans-synaptic Zn mobilization rapidly rescues social interaction two independent mouse models ASD. In mice lacking Shank2, an excitatory postsynaptic scaffolding...
Shank2 is a multidomain scaffolding protein implicated in the structural and functional coordination of multiprotein complexes at excitatory postsynaptic sites as well psychiatric disorders, including autism spectrum disorders. While strongly expressed cerebellum, whether regulates cerebellar synapses, or contributes to behavioral abnormalities observed −/− mice, remains unexplored. Here we show that mice reduced synapse density Purkinje cells association with levels proteins, GluD2 PSD-93,...
Shank2 is an excitatory postsynaptic scaffolding protein implicated in synaptic regulation and psychiatric disorders including autism spectrum disorders. Conventional -mutant ( −/− ) mice display several autistic-like behaviors, social deficits, repetitive hyperactivity, anxiety-like behaviors. However, cell-type-specific contributions to these behaviors have remained largely unclear. Here, we deleted specific cell types found that male lacking neurons CaMKII-Cre;Shank2 fl/fl show...
Abstract When somatic cells acquire complex karyotypes, they often are removed by the immune system. Mutant that evade surveillance can lead to cancer. Neurons with karyotypes arise during neurotypical brain development, but neurons almost never origin of cancers. Instead, mutations in bring about neurodevelopmental disorders, and contribute polygenic landscape neuropsychiatric neurodegenerative disease. A subset human harbors idiosyncratic copy number variants (CNVs, “CNV neurons”),...
Structural birth defects occur in approximately 3% of live births; most such lack defined genetic or environmental causes. Despite advances surgical approaches, pharmacologic prevention remains largely out reach.
Abstract NMDA receptor (NMDAR) and GABA neuronal dysfunctions are observed in animal models of autism spectrum disorders, but how these impair social cognition behavior remains unclear. We report here that NMDARs cortical parvalbumin (Pv)-positive interneurons cooperate with gap junctions to promote high-frequency (>80 Hz) Pv burst firing cognition. Shank2 –/– mice, displaying improved sociability upon NMDAR activation, show impaired representation inhibitory firing. Cortical neurons...
SALM1 (SALM (synaptic adhesion-like molecule), also known as LRFN2 (leucine rich repeat and fibronectin type III domain containing), is a postsynaptic density (PSD)-95-interacting synaptic adhesion molecule implicated in the regulation of NMDA receptor (NMDAR) clustering largely based on <i>in vitro</i> data, although its vivo</i> functions remain unclear. Here, we found that mice lacking SALM1/LRFN2 (<i>Lrfn2</i><sup>−/−</sup> mice) show normal excitatory synapses but altered function,...
Debate remains around anatomic origins of specific brain cell subtypes and lineage relationships within the human forebrain. Thus, direct observation in mature is critical for a complete understanding structural organization cellular origins. Here, we utilize mosaic variation types as distinct indicators clonal dynamics, denoted cell-type-specific Mosaic Variant Barcode Analysis. From four hemispheres from two different neurotypical donors, identified 287 780 variants (MVs), respectively...
Abstract Somatic mosaicism is defined as an occurrence of two or more populations cells having genomic sequences differing at given loci in individual who derived from a single zygote. It characteristic multicellular organisms that plays crucial role normal development and disease. To study the nature extent somatic autism spectrum disorder, bipolar focal cortical dysplasia, schizophrenia, Tourette syndrome, multi-institutional consortium called Brain Mosaicism Network (BSMN) was formed...
The neural crest generates numerous cell types, but conflicting results leave developmental origins unresolved. Here using somatic mosaic variants as cellular barcodes, we infer embryonic clonal dynamics of trunk crest, focusing on the sensory and sympathetic ganglia. From three independent adult neurotypical human donors, identified 1,278 deep whole-genome sequencing, then profiled allelic fractions in 187 anatomically dissected We found a massive rostrocaudal spread progenitor clones...
Shank2 is an excitatory postsynaptic scaffolding protein strongly implicated in autism spectrum disorders (ASDs). -mutant mice with a homozygous deletion of exons 6 and 7 ( -KO mice) show decreased NMDA receptor (NMDAR) function autistic-like behaviors at juvenile [∼postnatal day (P21)] adult (&gt;P56) stages that are rescued by NMDAR activation. However, ∼P14, these the opposite change – increased function; moreover, suppression activity early, chronic memantine treatment during P7–21...
Introductory paragraph Mosaic variants (MVs) reflect mutagenic processes during embryonic development 1 and environmental exposure 2 , accumulate with aging, underlie diseases such as cancer autism 3 . The detection of MVs has been computationally challenging due to sparse representation in non-clonally expanded tissues. While heuristic filters tools trained on clonally high allelic fractions are proposed, they show relatively lower sensitivity more false discoveries 4–9 Here we present...
Abstract Malformations of cortical development (MCD) are neurological conditions displaying focal disruption architecture and cellular organization arising during embryogenesis, largely from somatic mosaic mutations. Identifying the genetic causes MCD has been a challenge, as mutations remain at low allelic fractions in brain tissue resected to treat epilepsy. Here, we report atlas 317 resections, identifying 69 mutated genes through intensive profiling mutations, combining whole-exome...