Wanjin HONG

Protein Trafficking and Cancer Cell Biology

Profile

Wanjin HONG
Lab Location: 
#5-18   Email: mcbhwj@imcb.a-star.edu.sg   Tel: 65869606

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. He was the recipient of National Science Award in 1999 in Singapore. Presently, he is a Professor and Executive Director of IMCB. He serves as the Editor-in-Chief of Bioscience Reports and is on the editorial board of TRAFFIC.

Research

Protein Trafficking and Cancer Cell Biology

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.

His early works identified the transmembrane domain as the targeting signal for Golgi-localized integral membrane proteins such as β-galactoside α2,6-sialyltransferase and N-acetylglucosaminyltransferase I, as well as the cytoplasmic Tyr-based targeting signal for TGN38. He also revealed that Brefeldin A selectively inhibited apical membrane trafficking in some polarized epithelial cells. His lab cloned the mammalian KDEL receptor and established the functional conservation of the retrograde recycling pathway to retrieve luminal proteins of the endoplasmic reticulum. His lab has contributed significantly to the identification and functional characterization of numerous proteins participating in membrane trafficking in mammalian cells. Half of the 40 or so known mammalian SNAREs, which participate in vesicle fusion events, were independently identified and functionally studied his lab. His collaboration with the Curie Institute has revealed that the VAMP4-Syntaxin6-Syntaxin16-Vti1a SNARE complex mediates retrograde transport from the early endosome to the trans-Golgi network (TGN). Using gene knockout mice, he and his collaborators have established a physiological role for endobrevin/VAMP8 in the regulated secretion by acinar cells of several exocrine organs, and that of several secretory cells in the circulation and kidney collecting duct cells. His lab is among the first few to independently discover that the phox (PX) domain represents a new motif for interacting with phosphoinositides, unveiling a novel mechanism for the cell to integrate diverse cellular processes via a spectrum of about 47 PX domain proteins. His independent and collaborative studies of SNX27 (a PX-domain sorting nexin) using knockout mice suggest that SNX27 may act as part of a general endosomal sorting machinery for membrane proteins (such as GPCRs and ion channels) containing type I PZD-binding motif. Defects in SNX27 impaired the recycling of post-synaptic NMDA receptors. His lab also contributed to the understanding of the molecular mechanisms governing the action of small GTPases such as Arl1, Rab7 and Rab34. His lab was amongst the first few to reveal that Arl1 functions to recruit GRIP-domain Golgin-97 and Golgin-245 on the TGN to regulate endosomal traffic back to the Golgi apparatus. The collaborative work with Haiwei Song’s lab has revealed a novel mode of action of small GTPases in that two Arl1 molecules interact with dimerized effectors. A similar mode of action was also revealed for Rab7 and its effector (RILP). RILP was identified as a common effector for Rab7, Rab34 and Rab36. His works also contributed to the current understanding of COPII in protein export from the ER, COG complex involved in Golgi function and human diseases called congenital disorders of glycosylation (CDG), and Tom1 VHS domain protein family in post-Golgi sorting.

He has also made significant contributions in the field of cancer cell biology. His early works demonstrated that E2F1 is sufficient to confer oncogenic growth. He has identified human Hbrm as a novel interacting protein of the tumor suppressor retinoblastoma protein. His recent work has demonstrated that TAZ is a novel oncogene and is able to promote cell migration, invasion and tumorigenesis. The oncogenic function is dependent on its ability to interact with TEAD transcriptional factors. His lab also uncovered the functional importance of TAZ/YAP interaction with Wbp2, as well as identified Axl receptor tyrosine kinase as a downstream target gene of TAZ/YAP-TEADs in mediating oncogenic events. Angiomotin family proteins were identified as negative regulators of TAZ/YAP. His collaborative works resolved the X-ray structure of YAP-TEAD4 and Vgll1-TEAD4 complexes.

His future studies will focus on the physiological role of two SNAREs (VAMP8 and VAMP5), three PX-domain sorting nexins (SNX3, SNX12 and SNX27) and two small GTPases (Rab34 and Rab36) by analyzing the knockout mice. The mechanism governing the role of TAZ/YAP in promoting invasiveness of breast cancer or other cancers will be studied by focusing on interacting proteins and downstream target genes. This is particularly significant because TAZ and YAP are downstream targets of the Hippo pathway. The objective is to ultimately identify and design novel candidates that will modulate the activity of TAZ/YAP as either anti-cancer drugs or regenerative medicines for tissue repair.

Staff

Department: Wanjin HONG

Name: Ajaybabu Venkatesan POBBATI

Designation: Senior Research Fellow

Email: ajaybabuvp@imcb.a-star.edu.sg


Name: Sayan CHAKRABORTY

Designation: Senior Research Fellow

Email: sayanc@imcb.a-star.edu.sg


Name: John HELLICAR

Designation: ARAP Student

Email: hellicarj@student.imcb.a-star.edu.sg


Name: Yan Shan ONG

Designation: Research Fellow

Email: ongys@imcb.a-star.edu.sg


Name: Siew Wee CHAN

Designation: Research Scientist

Email: mcbcsw@imcb.a-star.edu.sg


Name: Yik Loo TAN

Designation: Senior Laboratory Officer

Email: mcblab49@imcb.a-star.edu.sg


Name: Cheng Chun WANG

Designation: Research Scientist

Email: wangcc@imcb.a-star.edu.sg


Name: Kizito Ngwa NJAH

Designation: SINGA Student

Email: knjah@student.imcb.a-star.edu.sg


Publications

PUBLICATIONS (total citations about 8,100 & H-index of 52)

Selected Publications

Toloczko, A., Guo, F., Yuen, H.F., Wen, Q., Wood, S.A., Ong, Y.S., Chan. P.Y., Shaik, A.A., Gunaratne J, Dunne MJ, Hong W, Chan SW.

Deubiquitinating Enzyme USP9X Suppresses Tumor Growth via LATS Kinase and Core Components of the Hippo Pathway.
Cancer Res. (2017) 77, 4921-4933.

Liu, C.Y., Pobbati, A.V., Huang, Z., Cui, L., and Hong, W.

Transglutaminase 2 is a direct target gene of YAP/TAZ-Letter.
Cancer Res. (2017) 77, 4734-4735.

Chakraborty, S., Njah, K., Pobbati, A.V., Lim, Y.B., Raju, A., Lakshmanan, M., Lim, C.T., and Hong W.

Agrin as a mechanotransduction signal regulating YAP through the Hippo Pathway.
Cell Reports (2017) 18, 2464-2479. 
(Discovered the first link of Agrin to mechanotransduction; highlighted in Trends in Cancer)

Chakraborty, S., Lakshmanan, M., Swa, H.L.F., Chen, J.X., Zhang, X.Q., Ong, Y.S., Loo, L.S., Akıncılar, S.C., Gunaratne, J., Tergaonkar, V., Hui, K.M., Hong, W.

An oncogenic role of Agrin in regulating focal adhesion integrity in Hepatocellular carcinoma.
Nature Commun. (2015) 6:6184. doi: 10.1038/ncomms7184 
(Defined the role and mechanism of Agrin in Hepatocellular carcinoma and suggested it as a potential diagnostic and therapeutic target)

Loo, L.S., Tang, N., Al-Haddawi, M., Dawe, G.S., and Hong, W. A role of sorting nexin 27 in AMPA receptor trafficking.

Nature Commun. (2014) Jan 24;5:3176. doi: 10.1038/ncomms4176. 
(Revealed a role of SNX27 in postsynaptic recycling of neurotransmitter receptors)

Chan, S.W., Lim, C.J., Guo, F., Tan, I., Leung, T., and Hong W.

Actin-binding and Cell Proliferation Activities of Angiomotin Family Members Are Regulated by Hippo Pathway-mediated Phosphorylation.
 J. Biol. Chem. (2013) 288, 37296-37307. 
(Highlighted by F1000Prime as being of special significance in its field)


Selected peer-reviewed original research articles (from 1992)
1. Wang, X., Zhao, Y., Zhang, X., Badie, H., Zhou, Y., Mu, Y., Loo, L.S., Cai, L., Thompson, R.C., Yang, B., Chen, Y., Johnson, P.F., Wu, C., Bu, G., Mobley, W.C., Zhang, D., Gage, F.H., Ranscht, B., Zhang, Y.W., Lipton, S.A., Hong, W., and Xu, H. 
Loss of sorting nexin 27 contributes to excitatory synaptic dysfunction by modulating glutamate receptor recycling in Down's syndrome. 
Nature Medicine (2013) 19, 473-480. (with Cover image and  News and Views)

2. Zhu, D., Zhang, Y., Lam, P.P., Dolai, S., Liu, Y., Cai, E.P., Choi, D., Schroer, S.A., Kang, Y., Allister, E.M., Qin, T., Wheeler, M.B., Wang, C.C., Hong, W., Woo, M., Gaisano, H.Y. 
Dual Role of VAMP8 in Regulating Insulin Exocytosis and Islet β Cell Growth. 
Cell Metabolism (2012) 16, 238-249. (highlighted by A-IMBN research)

3. Pobbati, A.V., Chan, S.W., Lee, I., Song, H., Hong, W. 
Structural and functional similarity between the Vgll1-TEAD and the YAP-TEAD complexes. 
Structure (2012) 20, 1135-1140. (revealed structural similarity of Vgll1-TEAD and YAP-TEAD complexes)
(highlighted by A*STAR research)

4. Chan, S.W., Lim, C.J., Chong, Y.F., Venkatesan Pobbati, A., Huang, C.X., and Hong, W. 
Hippo pathway-independent regulation of TAZ and YAP by Angiomotin family. 
J. Biol. Chem. (2011) 286, 7018-7026. (Identified angiomotin as a novel regulator of TAZ and YAP in the Hippo pathway) (highlighted by A*STAR research)

5. Cai, L., Loo, L.S., and Hong, W. 
Deficiency of Sorting Nexin 27 (SNX27) Leads to Growth Retardation and Elevated Levels of N-methyl-D-aspartate (NMDA) Receptor 2C (NR2C). 
Mol. Cell. Biol. (2011) 31, 1734-1747. (Defined that SNX27 is a general endosomal sorting protein for surface proteins with PDZ-binding motifs) (highlighted by A*STAR research)

6. Chan, S.W., Lim, C.J., Huang, C.X., Chong, Y.F., Gunaratne, H.J., Hogue, K.A., Blackstock, W.P., Harvey, K.F., and Hong, W. 
WW domain-mediated interaction with Wbp2 is important for the oncogenic property of TAZ. 
Oncogene (2011) 30, 600-610. (Showed that Wbp2 is a regulator of the Hippo pathway by acting as a positive factor for TAZ and YAP) (Highlighted by A*STAR research)

7. Yan Shan Ong, Y.S., Tang, B.L., Loo, L.S., and Hong, W. 
p125A exists as part of the mammalian Sec13-Sec31 COPII subcomplex to facilitate ER-Golgi transport. 
J. Cell Biol. (2010) 190, 331-345. (Showed that p125 co-exists with Sec13-Sec31 as a complex to regulate COPII export from the ER) (Highlighted by A*STAR research)

8. Chen, L.M., Chan, S.W., Zhang, X.Q., Walsh, M., Lim, C.J., Hong, W., Song, H.W. 
Structural basis of YAP recognition by TEAD4 in the Hippo pathway. 
Genes & Dev.(2010) 24, 290-300. (Solved the x-ray structure of YAP-TEAD4 protein complex of the Hippo pathway) (Highlighted by A*STAR research)

9. Wang, C.C., Ng, C.P., Shi, Hong, Liew, H.C., Guo, K., Zeng, Q., and Hong, W.
A role of VAMP8/endobrevin in surface deployment of the water channel aquaporin 2. 
Mol. Cell. Biol.(2010) 30, 333-343. (Showed that VAMP8 is important for vasopressin-induced surface fusion of AQP-2 vesicles)

10. Liu, N. S., Loo, L.S., Loh, E., Seet, L.F. and Hong, W. 
Participation of Tom1L1 in EGF-stimulated endocytosis of EGF receptor. 
The EMBO J. (2009) 28, 3485-3499. (Showed that Tom1L1 is likely a regulated adaptor for EGF-stimulated endocytosis of EGF receptor) (Highlighted by A*STAR research)

11. Chan, S.W., Lim, C.J., Loo, L.S., Chong, Y.F., Huang, C., and Hong, Hong, W. 
TEADs mediate nuclear retention of TAZ to promote oncogenic transformation. 
J. Biol. Chem. (2009) 284, 14347-14358. (Revealed that interaction with TEAD1-4 is important for TAZ to transform cells)

12. Chan, S.W., Lim, C.J., Guo, K., Ng, C.P., Lee, I., Hunziker, W., Zeng, Q., and Hong, W. 
A role for TAZ in migration, invasion and tumorigenesis of breast cancer cells. 
Cancer Res. (2008) 68, 2592-2598. (Revealed that TAZ is likely a new oncogene for invasive breast cancer)

13. Tran, T.T.H, Zeng, Q., and Hong, W. 
VAMP4 cycles from the surface to the trans-Golgi network via the sorting and recycling endosome. 
J. Cell Sci. (2007) 120, 1028-1041. (Highlighted in This Issue of JCS 120, e601).

14. Wang, C.C., Shi, H., Guo, K.,  Ng, C.P.,  Li, J., Gan, B.Q., Liew, H.C., Leinonen, J., Rajaniemi, H., Zhou, Z.H., Zeng, Q., and Hong, W. 
VAMP8/endobrevin as a general v-SNARE for regulated exocytosis of the exocrine system.
Mol. Biol. Cell (2007) 18, 1056-1063. (Showed that VAMP8 is a major SNARE responsible for regulated exocytosis of the exocrine system)

15. Wu, M.S., Wang, T.L., Loh, E., Hong, W., and Song, H.W. 
Structural basis for recruitment of RILP by small GTPase Rab7. 
The EMBO J.(2005) 24, 1491-1501. (Resolved the structural basis for Rab7 GTPase interaction with its effector)

16. Wang, C.C., Ng, C.P., Lu, L., Atlashkin, V., Zhang, W., Seet, L.F., and Hong, W. 
A role of endobrevin/VAMP8 in regulated exocytosis of pancreatic acinar cells. 
Dev. Cell (2004) 7, 359-371. (Highlighted in Sept 23, 2004 issue of Nature 431, 412).

17. Loh, E., and Hong, W. 
The binary interacting network of the conserved oligomeric Golgi (COG) tethering complex. 
J. Biol. Chem. (2004) 279, 24640-24648. (Defined the interaction map of COG complex)

18. Wu, M., Lu, L., Hong, W., and Song, H. 
Structural Basis of Recruitment of GRIP Domain Golgin-245 by Small GTPase Arl1. 
Nature Struct. Mol. Biol. (2004) 11, 86-94. (Revealed a novel structural mechanism for small GTPases to interact with effector proteins)

19. Lu, L., and Hong, W.  
Interaction of Arl1-GTP with GRIP domains recruits autoantigens Golgin-97 and Golgin-245/p230 onto the Golgi.  
Mol. Biol. Cell (2003) 14, 3767-3781. (Defined the mechanism for Arl1 GTPase to regulate the Golgi apparatus)

20. Wang, T.L., and Hong, W.  
Inter-organellar regulation of lysosome positioning by the Golgi apparatus through Rab34 interaction with Rab-interacting lysosomal protein RILP. 
Mol. Biol. Cell (2002) 13, 4317-4332. (Defined a mechanism to regulating lysosomal positioning)

21. Loh, E., and Hong, W. 
Sec34 is involved in ER-Golgi transport in mammalian cells and exists in a complex(s) containing GTC-90 and ldlB. 
J. Biol. Chem. (2002) 277, 21955 321961. (Identified a novel protein complex called COG in regulating the Golgi apparatus) 

22. Mallard, F., Tang, B.L., Galli, T., Antony, C., Xu, Y., Claude, A., Hong, W., Bruno, G., Johannes, L. Early/recycling endosomes-to-TGN transport involves two SNARE complexes and a Rab6 isoform. J. Cell Biol. (2002) 156, 653-664.(Established a role of a novel SNARE complex in endosome-Golgi traffic) 

23. Xu, Y., Hortsman, H., Seet, L.F., Wong, S.H., and Hong, W. 
SNX3 regulates endosomal function via its PX domain-mediated interaction with PtdIns(3)P. 
Nature Cell Biology (2001) 3, 658-666. (Highlighted in June 29, 2001 issue of Cell 105, 817-820 & Aug issue of Nature Cell Biology 3, E179-182).

24. Zhang, T., Wong, S.H., Tang, B.L., Xu, Y., Peter, F., and Hong, W. 
The mammalian protein (rbet1) homologous to yeast Bet1p is primarily associated with the pre-Golgi intermediate compartment and is involved in vesicular transport from the endoplasmic reticulum to the Golgi apparatus. 
J. Cell Biol.  (1997) 139, 1157-1168. (Defined the function and mechanism of a novel mammalian SNARE)

25. Lowe, S.L., Peter, F., Subramaniam, V.N., Wong, S.H., and Hong, W. 
A SNARE involved in protein transport through the Golgi apparatus. 
Nature (1997) 389, 881-884. (Identified one of the first few SNAREs of the Golgi apparatus)

26. Xu, Y., Wong, S.H., Zhang Tao, Subramaniam, V.N., and Hong, W. 
GS15, a 15-kilodalton Golgi SNARE homologous to rbet1.  
J. Biol. Chem. (1997) 272, 20162-20166. (Identified one of a novel SNARE of the Golgi apparatus)

27. Tang, B.L., Peter, F., Krijnse-Locker, J., Low, S.H., Griffiths, G., and Hong, W. 
The mammalian homolog of yeast Sec13p is enriched in the intermediate compartment and is essential for protein transport from the endoplasmic reticulum to the Golgi apparatus. 
Mol. Cell Biol. (1997) 17, 256-266. (Showed that vesicle budding from the ER occurs in specific sites)

28. Subramaniam, V.N., Peter, F., Phil, R., and Hong, W. 
GS28, a 28 kDa Golgi SNARE that participates in ER-Golgi transport. 
Science (1996) 272, 1161-1163. (Identified one of the first few SNAREs of the Golgi apparatus)

29. Lowe, S.L., Wong, S.H. and Hong, W.
The mammalian ARF-like protein 1 (Arl1) is associated with the Golgi complex. 
J Cell Sci. (1996) 109, 209-220. (Revealed for the first time that Arl1 GTPase is present in the Golgi apparatus)

30. Singh, P., Coe, J. and Hong, W. 
A role for retinoblastoma protein in potentiating transcriptional activation by the glucocorticoid receptor. 
Nature (1995) 374, 562-565. (Identified hBrm as a novel interacting protein for retinoblastoma protein)

31. Subramaniam, V.N., Krijnse-Locker, J., Tang, B.L., Ericsson, M., Yosoff, A.R.bin M., Griffiths, G., and Hong, W. Monoclonal antibody HFD9 identifies a novel 28 kDa integral membrane protein on the cis-Golgi.    
J. Cell Sci. (1995) 108, 2405-2414. (Identified a novel Golgi membrane protein that turned out to be a novel Golgi SNARE)

32. Griffiths, G., Ericsson, M., Krijnse-Locker, J., Nilsson, T., Goud, B., Soling, H-D., Tang, B.L., Wong, S.H., and Hong, W. 
Localization of the KDEL receptor to the Golgi complex and the intermediate compartment in mammalian cells. 
J. Cell Biol. (1994) 127, 1557-1574. (Revealed the compartments of the recycling pathway to retrieve luminal ER proteins)

33. Singh, P., Wong, S.H., and Hong, W. 
Overexpression of E2F-1 in rat embryo fibroblasts leads to neoplastic transformation. 
The EMBO J. (1994) 13, 3329-3338. (Showed that E2F1 is sufficient for oncogenesis)

34. Tang, B.L., Wong, S.H., Qi, X.L., Low, S.H. and Hong, W. 
Molecular cloning, characterization, subcellular localization and dynamics of p23, the mammalian KDEL receptor. 
J. Cell Biol. (1993) 120, 325-338. (Revealed the molecular andDev. Cell (2004 functional conservation of a recycling pathway to retrieve luminal ER proteins)

35. Low, S.H., Tang, B.L., Wong, S.H., and Hong, W. 
Selective inhibition of protein targeting to the apical domain of MDCK cells by brefeldin A. 
J. Cell Biol. (1992)118, 51-62. (Defined a novel role of brefeldin A in regulating polarized membrane trafficking)

36. Wong, S.H., Low, S.H., and Hong, W. 
The 17-residue transmembrane domain of b-galactoside a2,6-sialyltransferase is sufficient for Golgi retention. 
J. Cell Biol. (1992) 117, 245-258. (Identified one of the first few signals for Golgi targeting of sugar transferases)


For complete list of publications, please click here