Research

I have been fascinated by the potential to repair and regenerate any tissues, a pursuit of regenerative medicine. Compared to humans, many organisms in nature exhibit more robust regenerative capabilities. The planarian Schmidtea mediterranea is a key, established research organism to study the mechanisms of tissue regeneration. Attracted by their regenerative and immortalization capacity in the context of development, people in my laboratory are eager to explore the mechanisms that govern tissue regeneration and that enable adult stem cells to achieve immortality.


1. Demonstrate the critical role of mitochondrial dynamics in tissue regeneration.

The process of regeneration, which requires the precise coordination of cell fate decisions with positional information, is highly conserved across different organisms. Mitochondrial dynamics, including their fusion, fission, selective degradation, transport, and associated metabolism, are critical for stem cell fate, development, and cellular repair. However, the mechanistic contributions of mitochondrial dynamics to large-scale tissue regeneration, including whole-body regeneration, remain largely unknown. Planarians offer an excellent model to investigate this process due to their remarkable regenerative abilities. We have found that regulation of the mitochondrial fusion–fission equilibrium by opa1 and drp1 plays a critical role in controlling planarian regeneration. This process is crucial for mitochondrial metabolism and mitonuclear balance, thereby regulating the expression of mitochondrial protein-encoding genes essential for planarian regeneration. Currently, we are taking efforts to resolve novel biologies related to this discovery in planarian regeneration.


2. Systematically identify factors required for planarian regeneration.

Identifying regulators for tissue and organism regeneration is fundamental for regenerative biology. While transcriptional changes have been widely used to identify regenerative regulators, this approach may overlook proteins regulated through post-transcriptional processes, resulting in few identified regulators at the protein level. My laboratory has recently identified pivotal factors required for planarian regeneration associated with translation regulation. This has significantly enhanced our understanding of planarian regeneration beyond mere transcriptional responses. To further dissect the molecular mechanisms of regeneration initiation, we are taking advantage of advanced multi-omics technologies to identify key regulators in the initiation of planarian regeneration.


3. Expanding toolkits for studying planarian regeneration.

Recent technological advancements have significantly boosted the use of planarians as a primary research organism for studying tissue regeneration. While advanced genomic technologies have been widely applied, cell culture and transgenesis have historically posed challenges in these remarkable organisms. The imaging methods for analyzing spatial information during regeneration have remained limited due to the constraints of traditional microscopy. To continuously address these challenges, we have made the following progress and are eager to develop more for planarian research.

(1) Development of new method to purify planarian stem cells suitable for cell culture, transplantation, and transfection.

(2) 3D whole-body imaging and reconstruction of planarians at subcellular resolution.


Inspired by the powerful regeneration ability of the planarians, we hope to extend our experitise to study aging and related neurodegenerative diseases. We have recently developed a neural-muscular organoid system to model amyotrophic lateral sclerosis (ALS) from patient-derived iPS cells. Collectively, we are dedicated to applying our discoveries to enhance our understanding of the mystery of tissue regeneration. We anticipate that this knowledge will contribute to advancements in the development of innovative therapeutic approaches for tissue injuries, aging and related neurodegenerative diseases.