Endocytosis Regulation in Different Cell Types
Endocytosis Regulation in Different Cell Types
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Have you ever played with a LEGO 3-in-1 set and thought, “Wow, that’s clever!”? Our bodies do something even more impressive. They build over 200 different cell types using the same set of DNA. Isn’t that amazing?
In our lab, we study how cells fine-tune gene expression, alternative splicing, and other regulatory mechanisms to adapt a fundamental membrane trafficking pathway—clathrin-mediated endocytosis (CME)—to their specific needs. This allows each cell type to internalize distinct sets of molecules from the environment and respond to signals in unique ways.
CME is a highly conserved process essential for nutrient uptake, receptor recycling, and signal transduction. While the core components of CME are well characterized, its regulation can differ significantly across cell types and developmental stages.
We use genome editing, advanced live-cell imaging, and quantitative analysis to investigate endocytosis (see figures) in various human induced pluripotent stem cell (hiPSC)-derived cell types. By comparing endocytic dynamics across cell types in an isogenic background (cells with the same genome), we aim to uncover how cell identity shapes the composition of the endocytic machinery, its protein interaction networks, and ultimately, the endocytosis rate and specificity of cargo selection.
These insights are critical for understanding how endocytosis supports specialized cellular functions—and how its misregulation contributes to human disease.
Figure References:
Jin*, Shirazinejad* et al., 2022. Nature Communications
Jin et al., 2024. Cell Reports
Regulation of Membrane Trafficking Pathways Under Stress
Regulation of Membrane Trafficking Pathways Under Stress
Cells constantly adapt their membrane trafficking pathways in response to physiological and environmental stressors. Our lab investigates how key processes, particularly endocytosis and autophagy, a conserved lysosomal degradation and recycling pathway, are regulated under stress conditions such as nutrient deprivation.
We are particularly interested in how different trafficking pathways coordinate with and influence one another to maintain cellular homeostasis, and how these adaptations vary across cell types and during differentiation. These studies not only illuminate fundamental aspects of cell biology and physiology, but also provide insight into how trafficking defects contribute to developmental and neurodegenerative diseases.
Membrane Trafficking in Rare Diseases
Membrane Trafficking in Rare Diseases
While each rare disease affects fewer than 1 in 2,000 individuals, more than 10,000 rare diseases collectively impact over 300 million people worldwide. Many of these diseases are caused by mutations in a single gene, yet the functions of many disease-linked genes remain poorly understood.
In collaboration with Dr. Zepeng Yao, we are investigating how defects in membrane trafficking pathways, particularly autophagy and endocytosis, contribute to the development of rare diseases.
By combining Drosophila (fruit fly) and human iPSC models, we aim to determine when and where mutations in membrane trafficking genes exert their effects. Leveraging the extensive collection of tissue-specific drivers in Drosophila, the Yao Lab can identify the specific tissues and developmental stages most vulnerable to these mutations. These findings will guide our use of tissue-specific cells differentiated from hiPSCs to model disease-relevant conditions and uncover the underlying cellular mechanisms.
This dual-model system provides a powerful, efficient, and cost-effective strategy to advance our understanding of rare disease biology and ultimately, we hope this knowledge will help pave the way toward new therapeutic approaches.
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