Dr. Yusong Guo obtained his PhD in Cell Biology, working in Prof. Adam Linstedt’s laboratory at Carnegie Mellon University. Then he performed his postdoctoral research in Prof. Randy Schekman’s lab at UC Berkeley. In 2015, Dr. Guo started his independent academic career as an Assistant Professor at the Division of Life Science, Hong Kong University of Science and Technology.

Research Question

Molecular mechanisms regulating surface delivery of signaling receptors and signaling molecules in the secretory pathway

Signal transduction pathway is initiated by the interaction between signaling receptors on the target cell and signal molecules secreted by the producing cell. Although fundamentally important, it remains largely unclear how newly synthesized signal molecules and signal receptors are delivered to the plasma membrane to perform their physiological functions.

Utilizing systematic biochemical and cell biological approaches, we aim to understand the sorting and surface delivery of various transmembrane signaling receptors (planar cell polarity proteins and EGFR) and soluble signaling molecules (sonic hedgehog and Insulin-like growth factor-2) in the secretory pathway. These analyses provide novel insights into biosynthetic trafficking of these cargo proteins that is critical for them to perform their physiological functions. Our study also provides useful guidance on the development of novel inhibitors to downregulate the activity of a specific signaling receptor or signaling molecule by blocking its surface delivery process.

In addition, we have developed a large scale vesicle formation assay in combination with quantitative mass spectrometry analysis to profile proteins associated with transport vesicles. We aim to utilize this approach to reveal cargo clients that depends on a specific cellular factor to be packaged into transport vesicles. We also aim to utilize this approach to uncover novel factors that are associated with vesicles to mediate trafficking.

Representative Publications

(# Contributed equally, * corresponding authors, underlined authors are from the Guo lab)

1. Li T#, Yang F#, Heng Y, Zhou S, Wang G, Wang J, Wang J, Chen X, Yao ZP*, Wu Z* and Guo Y*. TMED10 mediates the trafficking of insulin like growth factor 2 along the secretory pathway for myoblast differentiation. PNAS (accepted)
2. Wang J, Lau PK, Li CW, Guo Y*. The clathrin adaptor complex-1 and Rab12 regulate post-Golgi trafficking of wild-type EGFR. Journal of Biological Chemistry. 2023. 299(3):102979.
3. Tang X, Chen R, Mesias VSD, Wang T, Wang Y, Poljak K, Fan X, Miao H, Hu J, Zhang L, Huang J, Yao S, Miller EA, Guo Y*. A SURF4-to-proteoglycan relay mechanism that mediates the sorting and secretion of a tagged-variant of sonic hedgehog. PNAS. 2022.119(11):e2113991119.
4. Huang Y#, Yin H#, Li B#, Wu Q, Liu Y, Poljak K, Maldutyte J, Tang X, Wang M, Wu Z, Miller EA, Jiang L, Yao Z*, and Guo Y*.  An in vitro vesicle formation assay reveals novel cargo clients and factors that mediate vesicular trafficking. PNAS. 2021.118(35):e2101287118.
5. Yang F, Li T, Peng Z, Liu Y, and Guo Y*. The amphipathic helices of Arfrp1 and Arl14 are sufficient to determine subcellular localizations. Journal of Biological Chemistry 2020.295(49):16643-16654.
6. Tang X, Zhang L, Ma T, Wang M, Li B, Jiang L, Yan Y, and Guo Y*. Molecular mechanisms that regulate export of the planar cell-polarity protein Frizzled-6 out of the endoplasmic reticulum. Journal of Biological Chemistry 2020.295, 8972-8987.
7. Niu L#, Ma T#, Yang F, Yan B, Tang X, Yin H, Wu, Q, Huang Y, Yao ZP, Wang, J., Guo Y.*, and Hu, J*.Atlastin-mediated membrane tethering is critical for cargo mobility and exit from the endoplasmic reticulum. PNAS. 2019. 116, 14029-14038.

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