Research Interests
Protein secretion is a major way for intercellular communication. Data from the Human Protein ATLAs show around 10% of human proteins are secretory proteins. These proteins play important roles in many biological processes, and its dysregulation may lead to multiple human diseases. Besides, secretory proteins are good drug targets. Of the 754 FDA-approved drugs with verified molecular targets, drugs targeting secretory proteins accounts for 14% (102 drugs), not including secretory proteins (e.g. insulin) themselves.
Unconventional protein secretion (UPS) refers to the release of cytosolic proteins without a signal peptide independent of ER-Golgi trafficking. UPS is usually induced by stress, and has been shown to regulate physiological processes (e.g. inflammation, development), and contribute to the pathogenesis of human diseases (e.g. cancer, neurodegeneration, metabolic diseases and pathogen infection). However, the mechanisms of UPS, the exact unconventional secretory cargoes, and its dysregulation in diseases are largely unclear. The goal of Dr. Zhang’s lab is to understand the biological nature of UPS as well as the function of UPS in human diseases especially neurodegenerative diseases. The lab uses cell biology, biochemistry, neuroscience and immunology methods to study the molecular mechanisms and function of UPS in inflammation and age-related diseases, as well as develop novel biomarkers for early diagnosis and drugs for therapeutic intervention. Our current research is mainly focused on: 1) dissecting the function and mechanism of TMED10-channelled UPS (THU) in human diseases; 2) potential THU or UPS chemical modulators in the treatment of age-related diseases.
Scientific Contributions
Most UPS cargoes enter into a vesicle carrier which exports them through membrane trafficking. How UPS cargoes enter into the vesicle and the identity of UPS carriers have been unknown. Our study identifies a transmembrane protein TMED10 as a protein channel on the ER-Golgi intermediate compartment (ERGIC) for translocation of multiple UPS cargoes into secretory vesicles. The work reveals a novel protein translocation pathway (TMED10-channelled UPS, THU) for UPS and opens a new direction in UPS research.
Selected Publications
1. Lei Liu,
Min Zhang*, Liang Ge*. Protein translocation into the ERGIC: an upstream event of secretory autophagy.
Autophagy, 2020, 16(7): 1358-1360.
2. Min Zhang#, Lei Liu#, Xubo Lin, Yang Wang, Ying Li, Qing Guo, Shulin Li, Yuxin Sun, Xuan Tao, Di Zhang, Xiachen Lv, Li Zheng, Liang Ge. A translocation pathway for vesicle-trafficking mediated protein unconventional secretion. Cell, 2020, 181(3): 637-652. Selected for F1000
3. Min Zhang and Liang Ge. Cell-Free reconstitution of autophagic membrane formation. Methods Mol Biol, 2019, 1880:135-148. doi: 10.1007/978-1-4939-8873-0_7. (Protocol; Book Chapter)
4. Min Zhang, Yu Wang and Liang Ge. Endomembrane remodeling and autophagic membrane generation. Autophagy, 2018, 14(5): 918-920.
5. Min Zhang, Dawei Liu and Liang Ge. In vitro dissection of autophagy. Curr Protoc Cell Biol, 2017, 77, 11.23.1–11.23.17. doi: 10.1002/cpcb.33
6. Min Zhang, Sam Kenny, Liang Ge, Ke Xu and Randy Schekman. Translocation of interleukin-1β into a vesicle intermediate in autophagy-mediated secretion. eLife, 2015, 4(e11205). Selected for F1000
7. Min Zhang and Randy Schekman. Unconventional secretion, unconventional solutions. Science, 2013, 340(6132):559-61.
8. Min Zhang, Jia-Li Zhang, Jin-Xiu Rui, and Xiao-Long Liu. p300-mediated acetylation stabilizes the Th-inducing POK factor. J. Immunol, 2010, 185: 3960-3969. (Highlighted as top 10% of the articles published in J. Immunol.)
9. Liang Ge, Min Zhang, Dawei Liu, Sam Kenny, Miharu Maeda, Kota Saito, Ke Xu, and Randy Schekman. Remodeling of ER-exit sites initiates a membrane supply pathway for autophagosome biogenesis. EMBO Report, 2017, 18(9): 1586-1603.
10. Livia W Brier, Min Zhang, Liang Ge. Mechanistically dissecting autophagy: insights from in vitro reconstitution. J Mol Biol, 2016, 8; 428(9 Pt A):1700-13.
11. Liang Ge, Min Zhang and Randy Schekman. Phosphatidylinositol 3-kinase and COPII generate LC3 lipidation vesicles from the ER-Golgi intermediate compartment. eLife, 2014, 3(04135).
12. Liang Ge, David Melville, Min Zhang and Randy Schekman. The ER-Golgi intermediate compartment is a key membrane source for the LC3 lipidation step of autophagosome biogenesis. eLife, 2013, 2(00947).
