Our laboratory is working on identifying the molecular mechanisms underlying how a pluripotent cell develops into a defined cell type of human brain, such as neurons, microglia, retinal ganglion cells and other neural lineages. This has allowed us to generate functional brain cells with high consistency at scale from human iPSCs, including patient-derived iPSCs or those carrying diseasespecific mutations by CRISPR/Cas9 technology, offering novel avenues for the development of human in vitro models to support research and drug discovery.

In the past four years, we used human iPSCs derived from familial and sporadic patients of Alzheimer’s disease (AD) to study disease mechanisms and to screen novel drugs for treatment. We differentiated the AD-iPSC lines into the neuronal lineage to examine whether these neurons have mature phenotypic and physiological properties, as well as AD-like biochemical features. We also established a novel protocol enabling differentiation of human microglia-like cells from hiPSCs in high purity, which is used to investigate the neuroinflammatory phenotypes of AD. In the future, AD-iPSC derived neurons and glial cells, plus 3D organoids, harboring disease properties will be used as humanized models to study the mechanisms underlying AD pathogenesis, as well as to evaluate potential drugs for AD treatment.

2001.09-2009.12 Molecular and Cellular Mechanisms of Neural Development

• General molecular experiments and biochemical assays (gene cloning, RT-PCR, western blot, etc.)
• General cell biological experiments (mammalian cell culture, immunocytochemistry, etc.)
• In vivo chick embryo manipulation (in ovo electroporation, immunohistochemistry, etc.)
• Phenotype analyses of transgenic mouse embryos

2010.08-2014.07 Mechanisms and Regulation of Neurotrophin Transport and Secretion

• In vitro live-cell imaging (time-lapse recording of single molecule tracking, FRET imaging, calcium imaging, and image analysis, etc.)
• General cell biological experiments (primary neuronal culture, immunocytochemistry, etc.)
• In vivo rat embryo manipulation (in utero electroporation, section and time-lapse imaging, immunohistochemistry, etc.)
• Viral vector package (lentivirus)

2014.08-presenst Modeling of Human Neurological Disorders Using Induced Pluripotent Stem Cells

• In vitro modeling of AD using patients’ iPSCs (human iPSC culture, neuron & microglia differentiation, 3D brain organoid, genome editing with CRISPR/Cas9 technology, etc.)
• Evaluation of drug candidate using AD-iPSCs (in vitro AD pathological phenotype assays)