Wanjin HONG graduated from Xiamen University (Fujian, China) in 1982 and was one of a few hundred Chinese students chosen for further graduate training in the United States via the CUSBEA program. He received his PhD from the State University of New York (SUNY Buffalo), and was a postdoctoral fellow there before he joined the Institute of Molecular and Cell Biology (IMCB) in Singapore as a principal investigator in 1989. At present, he is a Professor and Deputy Director for the Cancer and Developmental Cell Biology Division (CDCBD). He is currently the Editor-in-Chief for Bioscience Reports (BsR) and a member of the editorial board for several other journals, such as the Journal of Biological Chemistry (JBC), Traffic, and Molecular Membrane Biology (MMB).

Proteins encoded by the estimated 25,000 human genes must be targeted to the right sites for proper function, and many human diseases arise from defects in the protein trafficking process.  Protein traffic in the secretory and endocytic pathways governs many physiological processes such as the synaptic transmission of neurons, regulated exocytosis of the endocrine and exocrine systems, and regulated secretion by many cells in the circulation.  Protein trafficking also regulates signalling events and developmental processes. Studying the mechanisms of protein traffic will not only provide new insights into developmental and physiological biology but also offer new strategies to detect and treat human diseases such as diabetes and cancer.
The secretory pathway is composed of the endoplasmic reticulum (ER), the intermediate compartment, the Golgi apparatus and the plasma membrane. The endocytic pathway starts from the plasma membrane and consists of several different endosomal compartments and the lysosome. Protein transport along the secretory and endocytic pathways is mediated by various types of membrane-enclosed small vesicles or large containers. Vesicle-mediated transport can be roughly divided into three major steps: 1) vesicle formation, 2) vesicle targeting/tethering, and 3) vesicle docking and fusion with the acceptor compartment. Regulated fusion of vesicles/containers governs synaptic transmission and the function of secretory cells of the endocrine and exocrine systems.

Vesicle formation is mediated by a cytosolic coat protein complex. The COPII coat complex mediates protein export from the ER and is composed of Sar1p, Sec16p, the Sec23p-Sec24p subcomplex and the Sec13p-24p subcomplex in yeast. This research group has characterized the mammalian Sec13 and two distinct mammalian Sec31 isoforms. They have also shown that there are two distinct Sec23 and four distinct Sec24 isoforms in mammals. While continuing the study on the COPII coat, this group is embarking on a new project to study the mechanism governing the sorting/endocytosis and stability of surface EGF receptor in relation to signalling and tumorigenesis.

Vesicle tethering acts to position vesicles in the precise vicinity of the target compartment and to facilitate subsequent docking and fusion mediated by SNAREs. The group has identified a conserved oligomeric Golgi (COG) complex that consists of 8 proteins and regulates Golgi structure and function. The group has defined a novel regulatory pathway involving two small GTPases (ArfRP1 and Arl1) to regulate Golgi targeting of Golgin-97 and Golgin-245. The ArfRP1->Arl1->Golgin-97 pathway is believed to act in the tethering event of transport from the early/sorting endosome to the trans-Golgi network (TGN). They have also discovered that Rab34 and Rab7 GTPases share a common effector (RILP) to regulate the morphology and positioning of the lysosome.

Vesicle docking and fusion is mediated by pairings between the vesicle-associated SNARE (v-SNARE) and the target membrane SNARE (t-SNARE). Of the 38 known mammalian SNAREs, this group has independently identified and characterized more than half of them. The physiological roles of VAMP5 and VAMP8/endobrevin are being investigated using gene-targeting strategies to generate knockout mice. They have shown that VAMP8 is the primary v-SNARE responsible for regulated exocytosis of the exocrine system.

Regulated recruitment of cytosolic proteins onto the membrane is an emerging theme in cellular processes such as signalling and membrane traffic. This group’s discovery that Phox (PX)-domain is a novel motif for phosphoinositide interaction enables them to define the role of PX-domain containing proteins in regulating diverse cellular events, particularly in the endocytic pathway. Several sorting nexins (SNXs) such as SNX3, SNX12, and SNX27 are being investigated further by gene knockout in mice. The group has also defined a phosphoinositide-regulated pathway involving FYVE domain-containing endofin, TOM1, and clathrin in endosomal traffic.

In addition to continuing their research on SNAREs, small GTPase, and PX domain proteins using cellular, molecular and gene-targeting approaches, the group is now developing a new research program interfacing membrane traffic and cancer.  A systemic approach is being developed to identify new secreted factors that regulate the growth and tumorigenesis of cancer cells.  In view of the fact that K-ras is mutated in many colon and lung cancers, they are also focused on identifying secreted and membrane proteins whose expressions are altered by mutant K-Ras and are involved in tumorigenesis of colon and lung cancer.  The establishment of a role for TAZ in breast cancer cell migration and tumorigenesis enables them to test the hypothesis that the newly identified Hippo pathway may engage TAZ in cell contact inhibition, organ size control and cancer development. They aim to reveal novel insights into the interface of protein traffic and cancer so that new diagnostic, preventive and therapeutic strategies toward cancer of epithelial cells can be designed.

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