Principle: Cell state is governed by interacting regulatory landscapes, not single genes.

We develop tools and frameworks to precisely and durably control multi-gene regulation, enabling mechanistic dissection of cellular memory, stability, and reversibility. Our laboratory pioneered CRISPR-based transcriptional repression and activation and continues to innovate and expand programmable epigenetic control to interrogate and rewire epigenetic networks that underlie cell identity and disease.

Representative platforms:

• CRISPR interference and activation (CRISPRi/a) for causal perturbation of gene networks
• Compact CRISPR epigenetic editors for durable regulation at the chromatin layer
• Multiplexed perturbation strategies to map regulatory logic and state transitions

What this enables:

• Systematic, causal mapping of regulatory circuits controlling cell decisions and long-term memory
• Programmable writing/erasing of regulatory states to test sufficiency and reversibility
• Translation of principle-driven control systems toward durable therapeutic outcomes

Principle: Spatial organization is an active regulator of cell behavior, not a byproduct.

Cells organize genomes and transcripts in space and time to control function. We combine live-cell imaging, super-resolution microscopy, and CRISPR-based perturbation to study how nuclear architecture and RNA localization shape dynamic responses, often in real time. By linking spatial organization to causal perturbations, we move beyond static snapshots toward predictive understanding of how cells stabilize, adapt, and remember.

Representative platforms

• Live-cell DNA imaging and locus tracking to measure genome dynamics in single cells
• 3D genome manipulation to test how nuclear positioning and architecture influence regulation
• Programmable RNA localization (“RNA logistics”) to control where transcripts go and what they do

What this enables

• Mechanistic tests of how genome topology and RNA organization govern transcriptional programs
• Real-time readouts of cellular adaptation under controlled perturbations
• Discovery of general principles connecting nuclear organization to phenotype and function

Principle: Shared architectures govern multicellular systems, giving rise to emergent behaviors beyond those of any single cell.

We extend programmable control from individual cells to synthetic cell-cell communication by rewiring and interrogating how cells exchange signals, coordinate decisions, and collectively produce system-level phenotypes. By combining molecular perturbation, quantitative readouts, and principled design, we seek to understand how molecular interactions scale into multicellular dynamics, enabling cellular systems that exhibit emergent behaviors such as adaptation, memory, robustness, and coordinated responses. A particular focus is the bidirectional interplay between T cells and neurons, in which we investigate how programmable control of each cell type and their communication shape systems-level physiology and neurodegeneration.

Representative directions

• Programmable immune cell regulation to tune functional state, durability, and communication modes
• Neural and neuro-immune models to study long-term adaptation, repair, and coordinated dynamics
• Cross-lineage frameworks linking molecular control to emergent multicellular behaviors (communication, feedback, stability)

What this enables

• Design rules for building multicellular systems with robust, coordinated behaviors
• Mechanistic insight into immune–neural communication and systems-level phenotypes
• Translation of programmable control strategies toward therapies for otherwise intractable conditions