RESEARCH

 

Our laboratory is interested in the regulation of membrane dynamics and its impact on cell physiology and human health. Membranes are now known to be direct players in cell physiology, including organelles structure and biogenesis, membrane transport and intracellular trafficking as well as in dysfunctions leading to diseases. To maintain the proper composition and functions of these membranous structures, accurate and efficient delivery of proteins and lipids into these organelles is critical.

  Eukaryotes utilize membranous vesicles as major carriers to transport lipids andproteins between different organelles. To generate those carriers, membrane fission and fusion events involve highly energetically unfavorable changes in membrane topology and are thus orchestrated by protein fission and fusion machineries. Among those, the large GTPase dynamin is the most well-studied membrane fission machinery. Dynamin is the prototypical member of a family of GTPases and is best known for its role on clathrin-mediated endocytosis for mediating membrane fission.

  Mammals express three dynamins in a tissue specific manner; of these dynamin2 is ubiquitously expressed, and its mutations would cause two human congenital diseases: Charcot-Marie-Tooth Neuropathy (CMT) and Centronuclear Myopathy (CNM). Our laboratory currently uses dynamin to explore the underpinning of membrane trafficking defect leading to human tissue-specific diseases. Through the combination of comprehensive biochemical assays, cell biological experiments and transgenic animal establishment, we aim to elucidate the pathogenic mechanism of dynamin2-induced CNM and CMT.

  On the other hand, we are also interested in how eukaryotic cells cope with the environmental challenge in respect of regulating membrane dynamics. The mechanical environment plays an important role in regulating cellular function and behavior, including differentiation, proliferation, apoptosis and migration. Many researchers have been working on important cell biological questions about how the cell reacts to the rigidity of extracellular matrix (ECM).

  However, little is known about the membrane dynamics in different environmental stiffness, for example, endocytosis. Therefore, we explore the activity of individual endocytic pathway while cells are cultured on matrix with differential rigidity. Meanwhile, the content of cell surface proteins or lipids, and the mechanism of how ECM rigidity affects endocytic machineries will be characterized.

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