← Activated microglia (black) around amyloid plaque (blue)
iPS cell-derived human microglia in the mouse brain →
Research
The best part of science is knowing, for a moment, something that nobody else in the world knows.
Areas of investigation
Our lab is dedicated to unraveling the cellular mechanisms by which microglia and peripheral immune cells influence neuronal functions, either by providing support or causing damage. This fundamental understanding guides our parallel efforts to develop next-generation cell therapies for neurological diseases.
To achieve this, we use a multi-faceted approach, including:
(1) Cell-cell interaction screens using triculture- and mouse model with universal recording system
(2) CRISPR screens in iPS cell-derived microglia and peripheral myeloid cells
(3) Transcriptomic and epigenetic measurements
(4) Advanced cellular and biochemical assays
(5) Artificial intelligence as tools
Next-generation cell therapy
We have achieved a breakthrough with the development of a non-genetic, high-efficiency microglia replacement cell therapy. This innovative therapy has shown remarkable therapeutic efficacy in a Trem2-dependent Alzheimer's disease mouse model (Yoo et al., 2023).
Currently, we are further enhancing this therapy by engineering donor cells with precision, utilizing CRISPR genome editing techniques.
Genomics of neuro-immune interactions
Our lab is actively exploring the precise mechanisms governing the infiltration of peripheral myeloid cells into the brain.
We apply this research to two key areas: (1) the dynamics of microglia replacement and (2) the progression of neurodegenerative diseases, with in vivo CRISPR screens serving as a core investigative tool.
Elucidating disease mechanisms with brain-in-a-dish in vitro model
To unravel the complexities of neurological disease, our research focuses on building human 'brain-in-a-dish' models.
These cutting-edge 2D and 3D platforms, comprised of iPSC-derived neurons, astrocytes, and microglia, allow us to decipher the fundamental principles of intercellular communication in the brain and identify key dysregulations that lead to disease.
Neuron - microglia interaction during CNS development and neurological diseases
We recently developed advanced 2D neural triculture and 3D spheroid models, as well as iPS cell-derived human microglia chimeric brain (Yoo et al., In Revision). These models are meticulously designed with well-defined cell combinations to closely mimic the complex environment of the brain.
We're now leveraging this models to investigate research questions concerning microglial cell-cell interactions. To gain a comprehensive understanding, we're utilizing a universal recording system that allows us to observe these interactions both in vitro and in vivo.