劉雅雯 Ya-Wen Liu

研究骨骼肌膜重塑的調節
揭示肌肉發育與發病的分子和生物物理機制

I am deeply fascinated by the dynamic and fluid nature of biomembranes, and I am constantly intrigued by their impact on human health. In my research, I seek to understand how our bodies harness and regulate membrane remodeling, focusing on the development and disease pathogenesis of skeletal muscle. Specifically, I investigate a human hereditary myopathy known as centronuclear myopathy (CNM) to uncover its disease mechanism and reveal the molecular and mechanical underpinning of muscle development and physiology.

Our studies have revealed that the activity of the membrane fission GTPase dynamin-2 must be tightly controlled in muscle. Auto-activation of dynamin-2 resulting from CNM-associated mutations or hyper-activation due to abnormal insulin signaling and GSK3alpha-mediated phosphorylation can lead to enhanced membrane fission and endocytosis in muscle cells. Additionally, we investigate how muscle cell respond to mechanical stimulations such as stretching and relaxation. Our findings suggest that mechanical stretch-induced alteration in membrane tension stimulate mTOR activation and muscle growth through processes involving lipid-raft disruption, activation of phospholipase D2, increased phosphatidic acid production, and macropinosome formation.

In summary, our research contribute to the foundational understanding of muscle physiology, and provide insights into the therapeutic strategies for combating type II diabetes and sarcopenia.