Honors and Awards:
- Pew Scholar in Biomedical Sciences
- American Cancer Society Research Scholar
- American Heart Association Established Investigator Award
- Biology Department Teaching Award (2008)
Molecular mechanisms of exocytic trafficking, cell migration, and tumor invasion
Exocytosis is a basic cell biological process mediated by transport, docking, and fusion of secretory vesicles carrying proteins and lipids to the plasma membrane. Through exocytosis, hormones and neurotransmitters can be released. Also through exocytosis, membrane proteins and lipids can be incorporated into specific domains of plasma membrane for cell surface expansion, cell growth, morphogenesis, and cell migration. Our research aims to address three fundamental questions in cell biology: (1) what is the molecular basis for exocytosis; (2) how do the secretory machinery functions in concert with cytoskeleton and small-GTP-binding proteins during cell polarization and cell migration; (3) how the basic cell biolgical processes mentioned above are implicated in diseases such as cancer.
One of our research interests is the evolutionarily conserved multi-protein complex, named the exocyst. The exocyst consists of eight components: Sec3, Sec5, Sec6, Sec8, Sec10, Sec15, Exo70 and Exo84, and plays essential roles in secretory vesicle targeting and docking at the plasma membrane during exocytosis. The exocyst is specifically localized to sites of active exocytosis and polarized cell growth, and is a downstream effector of many small GTPases including Rab, Rho, and Ral. In addition, the exocyst is a direct target of many kinases in the cell. Under the control of these signaling proteins, the exocyst coordinates with actin cytoskeleton in many pathophysiological processes such as cytokinesis, ciliogeneisis, cell migration, and tumor invasion.
We are also interested in the molecular mechanisms that regulate the biogenesis and secretion of exosomes, which are lipid-encapsulated small vesicles secreted by many cells. Furthermore, we aim to understanding how cancer cell-derived exosomes and other types of extracellular vesicles communicate with tumor microenvironment and the immune system for cancer metastasis and immunosuppression.
We take a multiproned approach that combines biochemistry, biophysics, structure biology, molecular biology, genetics, and cell biology in our research. We also aim to connecting fundamental cell biology and clinical research, as we believe basic science and medicine can inspire and instruct each other.
Membrane traffic, exocytosis, exosomes, cell migration, morphogenesis, the exocyst complex, cytoskeleton, small GTPases, cancer, melanoma, metastasis.
- BIOL 205 (Cell Biology)
- BIOL 480/CAMB 480 (Advanced Cell Biology)
Chen, G., Huang, A., Zhang, W., Zhang, G., Wu, M., Xu, W., Yu, Z., Yang, J. Wang, B., Sun, H., Xia, H., Man, Q., Zhong, W., Antelo, L., Wu, B., Xiong, X., Liu, X., Guan, L., Li, T., Liu, S., Yang, R., Lu, Y., Dong, L., McGettigan, S., Somasundaram, R., Radhakrishnan, R., Mills, G., Lu, Y., Kim., J., Chen, YH., Dong, H., Zhao, Y., Karakousis, G.C., Mitchell, T.C., Schuchter, L.M., Herlyn, M., Wherry, E.J., Xu, X., Guo, W. Exosomal PD-L1 contributes to immunosuppression and is associated with anti-PD-1 response. NATURE (2018) 560:382-386.
Mei, K., Li, Y., Wang, S, Shao, G., Wang, J., Ding, Y., Luo, G., Yue, P. Liu, J., Wang, X., Dong, M-Q, Wang, H., W. Guo. Cryo-EM structure of the exocyst complex. NATURE Structural & Molecular Biology (2018) 25:139-146.
Lu, H., Liu, S., Zhang, G., Wu, B., Zhu, Y., Frederick, D., Hu, Y., Zhong, W., Randell, S., Sadek, N., Zhang, W., Chen, G., Cheng, C., Zeng, J., Wu, L., Zhang, J., Liu, X., Xu, W., Clemens Krepler, C., Sproesser, K., Xiao, M., Miao, B., Liu, J., Song, C., Liu, J., Karakousis, G., Schuchter, L., Yiling Lu, Y., Mills, G., Cong, Y., Chernoff, J., Guo, J., Boland, G., Sullivan, R., Wei, Z., Field, J., Amaravadi, R., Flaherty, K., Herlyn, M., Xu, X., Guo, W. PAK signaling drives acquired drug resistance to MAPK inhibitors in BRAF-mutant melanomas. NATURE (2017) 550:133-136.
Yue, P., Zhang, Y, Mei, K., Wang, S., Lesigang, J., Zhu, Y., Dong, G. and Guo, W. Sec3 promotes the initial binary
t-SNARE complex assembly and membrane fusion. NATURE COMMUNICATIONS (2017) 8:14236.
Lu, H., Liu, S., Zhang, G., Kwong L., Zhu, Y., Miller, J.P., Hu, Y., Zhong, W., Zeng, J., Wu, L., Krepler, C., Sproesser, K., Xiao, M., Xu, W., Karakousis, G.C., Schuchter, L., Field, J., Zhang, P.J., Herlyn, M., Xu, X., and Guo, W. Oncogenic BRAF-mediated melanoma cell invasion. CELL REPORTS (2016) 15: 2012-2024.
Wu, B., Guo, W. The Exocyst at a Glance. J. Cell Science (2015) 128(16):2957-64.
Wang, J., Ren, J., Wu, B., Feng, S., Cai, G., Tuluc, F., Peränen, J., and Guo, W. Activation of Rab8 guanine nucleotide exchange factor Rabin8 by ERK1/2 in response to EGF signaling. PNAS (2015) 112(1):148-153.
Das, A., Gajendra, S. Falenta, K., Oudin, O., Peschard, P. Feng, S. Wu, B., Marshall, C.J., Doherty, P.., ·Lalli, G., ·Guo, W. RalA promotes a direct exocyst-Par6 interaction to regulate polarity in neuronal development. (·co-corresponding authors). J. Cell Science (2014) 127: 686-699
Lu, H., Liu, J., Liu, S. Zeng, J., Ding, D., Carstens, R., Cong, Y., Xu, X., Guo, W. Exo70 isoform switching upon epithelial-mesenchymal transition regulates cancer cell invasion. Developmental CELL (2013) 27:560-573
Liu, J., Yang, C., Capraro, B., Baumgart, T., Bradley, R.P., Ramakrishnan, N.,
Xu, X. Radhakrishnan, R., Svitkina, T., Guo,
W. Exo70 generates membrane curvature for
morphogenesis and cell migration. Developmental
CELL (2013) 26, 266-278.
Luo, G., Zhang, J., Luca, F., Guo, W. Mitotic phosphorylation of Exo84 disrupts exocyst assembly and arrests cell growth. J. Cell Biol. (2013) 202 (1): 97-111.
Ren, J. and Guo, W. ERK1/2 regulates post-Golgi exocytosis through phosphorylation of the exocyst component Exo70. Developmental CELL (2012) 22(5):967-978.
Liu, J., Zhao, Y., Sun, Y., Yang, C., He, B., Goldman Y., Svitkina, T., Guo, W. Exo70 stimulates actin branching for lamellipodia formation and cell migration. Current Biology (2012) 22:1510-1515.
Das, A. and Guo, W. Rabs and exocyst in ciliogenesis, lumenogenesis and beyond. Trends in Cell Biol. (2011) 21(7) 383-386.
Orlando, K., Sun, X. Zhang, J. Lu, T., Yokomizo, L., Wang, P. and Guo, W. Exo-endocytic trafficking and the septin-based diffusion barrier are required for the maintenance of Cdc42p polarization during budding yeast asymmetrical growth. Mol. Biol. Cell (2011) 22:624-633.
Knödler, A., Feng, S., Zhang, X., Zhang, J., Das, A., Peränen, J. Guo, W. Coordination of Rab11 and Rab8 in primary ciliogenesis. PNAS (2010) 107 (14) 6346-6351.
Baek, K., Knödler, A., Lee, S., Zhang, X., Orlando, K., Zhang, J., Foskett, T.J., Guo, W*., Dominguez, D*. Structural basis for membrane and GTPase-binding by Sec3. J. Biol. Chem. (2010) 285(14):10424-33. (*co-corresponding authors).
Orlando, K., Zhang, J., Zhang, X., Yue, P., Chiang, T., Bi, E., and Guo, W. Regulation of Gic2 function by PI(4,5)P2 and Cdc42. J. Biol. Chem. (2008). 283:14205-14212.
Zhang, X., Orlando, K., He, B., Xi, F., Zhang, J., Zajac, A., and Guo, W. Membrane association and functional regulation of Sec3 by phospholipids and Cdc42. J. Cell Biol. (2008) 180(1): 145-158.
He, B., Xi, F., Zhang, X., Zhang, J., and Guo, W. Exo70 interacts with phospholipids and mediates the targeting of the exocyst to the plasma membrane. EMBO J. (2007) 26, 4053-4065.
He, B., Xi, F., Zhang, J., TerBush D., Zhang, X., and Guo, W. Exo70 mediates the secretion of specific exocytic vesicles at early stages of cell cycle for polarized cell growth. J. Cell Biol. (2007) 176(6):771-777.
Zuo, X., Zhang, J., Zhang, Y., Hsu, S., Zhou, D., and Guo, W. Exo70 interacts with the Arp2/3 complex and regulates cell migration. NATURE-Cell Biology (2006) 8(12):1383-1388.
Zajac, A., Sun, X., Zhang, J. and Guo, W. (2005) Cyclical Regulation of the Exocyst and Cell Polarity Determinants for Polarized Growth. Mol. Biol. Cell 16(3), 1500-1512.