1. Mechanisms regulating membrane and vesicle trafficking My research interest is to dissect the molecular mechanism involved in membrane and vesicle trafficking. My lab has been investigating the roles of small GTPases ADP-ribosylation factor (Arf)-like proteins (Arl) in regulating vesicular trafficking. We show that Arl1 and Arl3 play roles in trans-Golgi-mediated vesicular trafficking. We also demonstrate that ER stress mediates Arl1 activation to regulate vesicular transport at the Golgi. We will further explore the mechanisms of Arl1 and Arl3 in regulating vesicular traffic under cellular stresses. 2. Mechanisms of Arl4 small GTPases in regulating membrane and cytoskeletal dynamics We identified mammalian Arl4A and Arl4D and showed that Arl4D expression has tissue or differentiation specificity. We demonstrate that Arl4A is distributed in the nucleus and nucleolus, and is associated with early development, somite formation, and central nervous system differentiation. Arl4 subfamily proteins are associated with the initiation and progression of many cancers. Activation of Arl4 facilitates cell morphogenesis, de-creases actin filaments, and promotes cell migration. Hundreds of hereditary diseases, autoimmune diseases, and many cancers are known to be caused by the blocking of certain molecules transport in the cell. This project provides a platform to integrate basic research in Arl4 GTPases with the clinical application of identifying cancer biomarkers and potential drug targets. We will explore how Arl4 proteins be regulated to exert their function in membrane and cytoskeletal dynamics, thereby modulating cell migration, adhesion, invasion, and proliferation.
