RESEARCH
IN VIVO REPROGRMMING FOR TISSUE REPAIR
Research
In Vivo Reprogramming & Injury-Induced Regeneration
Tissue regeneration in adult mammals is fundamentally limited, and many organs rely on slow or incomplete repair processes after injury. However, recent discoveries show that somatic cells can temporarily revert to a more plastic, progenitor-like state—either naturally after injury or through controlled expression of reprogramming factors. Understanding and safely harnessing this transient dedifferentiation offers an entirely new therapeutic paradigm: instead of replacing damaged tissues, we can activate the body’s own regenerative capacity.
Our laboratory aims to define the principles governing these plasticity programs and to engineer precise, safe strategies for in vivo reprogramming. This work is significant not only for regenerative medicine but also for aging, organ failure, and diseases in which intrinsic repair mechanisms are insufficient.
Core Focus Areas
1. Decoding Injury-Induced Plasticity Programs
We investigate how tissues such as the intestine and liver naturally initiate regeneration by producing transient progenitor-like cells, uncovering shared molecular logic and organ-specific mechanisms that enable repair.
2. Engineering Safe Partial Reprogramming In Vivo
We develop methods for controlled, short-term induction of OSKM-based dedifferentiation—including mRNA–LNP delivery systems—to activate regenerative states without compromising cell identity or safety.
3. Restoring Regenerative Competence Across Organs
Using single-cell genomics, organoid models, and in vivo systems, we aim to enhance regeneration of damaged or aging tissues by manipulating temporally restricted reprogramming pathways.
Overall Goal
This research area bridges fundamental reprogramming biology with translational regenerative medicine, providing a framework to induce repair, rejuvenation, and functional recovery across diverse organs through controlled activation of cellular plasticity.
Precision Genome Editing & Human Stem-Cell Disease Modeling
We develop next-generation precision genome editing technologies and human pluripotent stem-cell platforms to understand and treat genetic diseases. Our work integrates engineered base/prime editing systems, isogenic stem-cell models, and advanced organoid and humanized tissue platforms. By combining these tools, we aim to reveal fundamental disease mechanisms and establish clinically relevant strategies for therapeutic genome correction.
Our approach focuses on three pillars:
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Enhancing Precision Editing in hPSCs
We investigate the unique DNA-repair biology of human pluripotent stem cells to engineer more accurate, efficient, and safe genome-editing systems optimized for therapeutic use. -
Building Human Disease Models Using Isogenic hPSCs and Organoids
We generate genetically defined, mutation-specific or mutation-agnostic human disease models to uncover pathogenic mechanisms across diverse disorders and to enable human-relevant therapeutic testing. -
Creating Translational Humanized Platforms
We construct in vivo humanized tissue systems derived from patient-specific stem cells to evaluate genome-editing therapeutics, RNA-based strategies, and cell therapies in settings that more faithfully mimic human biology.
Together, this research area establishes an integrated pipeline—from molecular tool development to stem-cell modeling and translational testing—that accelerates the discovery of curative therapies for inherited disorders.
Genetic alteration of PLURIPOTENT STEM CELLS
Human pluripotent stem cells (hPSCs) possess unique cellular and molecular properties that safeguard genomic integrity, setting them apart from somatic cells. Particularly, human embryonic stem cells (hESCs) exhibit robust DNA repair mechanisms and heightened vulnerability to genotoxic stressors. These attributes prompt swift cell death via mitochondria-mediated apoptosis upon DNA damage, preventing the passage of mutations to subsequent generations. The phenomenon of 'high mitochondrial priming' in hESCs contributes to rapid cell death upon DNA damage. Consequently, hPSCs tend to accumulate fewer mutations than somatic stem cells during in vitro culture. However, during in vitro maintenance, hPSCs often experience genetic abnormalities like recurrent copy number variations (CNVs), chromosomal abnormalities, and irregular mitosis. These anomalies pose risks to the safety of hPSC-based cell therapies. Nonetheless, the exact clinical implications and underlying mechanisms of these culture-induced (epi)genetic irregularities in hPSCs remain unclear.
Early Embryonic States & Pluripotency Regulation
The earliest stages of mammalian development involve rapid transitions between distinct cellular states, each defined by unique signaling, metabolic, and epigenetic landscapes. Understanding how naïve, formative, and primed pluripotency are established, maintained, and interconverted is essential for explaining developmental potential, cell-state stability, and lineage specification.
Our laboratory investigates the fundamental principles that govern these pluripotent states using embryonic stem cells, isogenic naïve–primed pairs, and embryo-inspired culture systems. By decoding the regulatory networks that drive state transitions, we aim to build a mechanistic framework that connects early embryogenesis with stem-cell engineering and regenerative biology.
Core Focus Areas
1. Signaling Networks that Define Pluripotency States
We study how pathways such as LIF–STAT3, FGF–ERK, Wnt–β-catenin, and phosphatase-based modulation orchestrate the balance between naïve and primed pluripotency, shaping cell identity and developmental competence.
2. Metabolic Regulation of Naïve–Primed Transitions
Distinct metabolic programs—OXPHOS-driven naïve cells versus glycolytic primed cells—serve as both drivers and readouts of pluripotent states. We investigate how energy metabolism, redox balance, and lipid utilization govern potency and cell-state stability.
3. Embryo-Inspired Platforms for Stem-Cell State Engineering
Using isogenic hPSC models, metabolic sensors, and single-cell approaches, we dissect how pluripotent states are established and reprogrammed, enabling rational control of stem-cell identity for developmental studies and future therapeutic applications.
Overall Goal
This research theme aims to provide a mechanistic roadmap of early embryonic pluripotency that informs stem-cell engineering, regenerative strategies, and the understanding of human developmental biology.
