← 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
Cell-cell 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.
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.
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.
Current working models: Rett syndrome, Leigh Syndrome, Autism spectrum disorders
Dissecting microglia receptors using AI
Leveraging advanced tools for novel protein design, our lab is keenly interested in applying artificial intelligence to engineer designer microglia.
These engineered cells are intended to carry out diverse therapeutic functions, such as sensing and destroying protein aggregates, or effectively replacing resident microglia in neurological contexts.