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Development of genetic and molecular tools to observe human brain development processes
Development of genetic and molecular tools to observe human brain development processes
The human brain is one of the most inaccessible organs in the human body. We aim to develop multi-omic approaches, including Single-cell genomics and duplex sequencing, that can accurately reconstruct human brain development and related disease processes.
1. Chung C*, Yang X*, et al., Gleeson JG. Cell-type-resolved mosaicism reveals the clonal dynamics of the human forebrain (2024) Nature, 629:384-392
2. Chung C*, Yang X*, et al., Gleeson JG. Comprehensive multi-omic profiling of somatic mutations in malformations of cortical development. (2023) Nat. Genet., 55:209-220 (Cover selected)
3. Yang X, Xu X, Breuss MW, Antaki D, Ball LL, Chung C, et al., Gleeson JG. Control-independent mosaic single nucleotide variant detection with DeepMosaic (2023) Nat. Biotechnol., DOI:10.1038/s41587-022-01559-w
Reconstructing brain cell lineages in humans
Reconstructing brain cell lineages in humans
Because human brain development is often inferred from model organisms, obtaining direct evidence has been challenging. However, mosaic variant barcode analysis (MVBA) provides non-invasive access to donor brains, enabling the reconstruction of lineage information imprinted during fetal development. By integrating MVBA with other multi-omics data, we aim to uncover the cellular origins and developmental pathways of the human brain and associated disorders, including brain malformations, autism spectrum disorders, and brain tumors.
1. Chung C*, Yang X*, et al., Gleeson JG. Cell-type-resolved mosaicism reveals the clonal dynamics of the human forebrain (2024) Nature, 629:384-392
2. Breuss MW, Yang X, Schlachetzki JCM, Antaki D, Lana AJ., Xu X, Chung C, et al., Glass CK, Gleeson JG. Somatic mosaicism reveals clonal distributions of neocortical development. (2022) Nature, 604:689-696
Architecting alternative brain models reflecting the human developmental processes
Architecting alternative brain models reflecting the human developmental processes
Although numerous attempts have been made to model brain disease phenotypes using traditional brain development models such as mice and organoids, discrepancies remain between these models and actual patients. Therefore, it is essential to develop models that more accurately reflect the brain developmental processes of patients. We aim to develop alternative models that precisely mimic human brain development. These models will facilitate accurate disease phenotype modeling and the development of new therapeutic strategies.
1. Chung C, Girgiss J, Gleeson JG. A comparative view of human and mouse telencephalon inhibitory neuron development. (2025) Development, 152(1):dev204306
2. Chung C, Shin W, Kim E. Early and late corrections in mouse models of autism spectrum disorders. (2022) Biol. Psychiatry, 91(11):934-944
3. Chung C*, Ha S*, et al., Kim E. Early correction of NMDAR function improves autistic-like behaviors in adult Shank2–/– mice. (2019). Biol Psychiatry, 85:534-543 (Selected as Priority Communications)
4. Kim R*, Kim J*, Chung C*, et al., Kim E. (2018). Cell type-specific Shank2 deletion in mice leads to differential synaptic and behavioral phenotypes. J Neurosci, 38(17):4076-4092
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