1987.09 - 1991.07  Department of Biochemistry, Anhui University, B.S. in Biochemistry

1991.09 - 1994.07  Beijing Institute for Cancer Research, Beijing Medical University, M.S. in Tumor Biology

1994.09 - 2001.01  Department of Molecular Genetics, Albert Einstein College of Medicine, Ph.D. in Molecular Genetics

2001.02 - 2004.03  Massachusetts General Hospital Cancer Center, Harvard Medical School, Research Fellow, February

2004.03 - 2004.07  Instructor, Massachusetts General Hospital Cancer Center, Harvard Medical School

2004.07 - 2009.09  Assistant Investigator, National Institute of Biological Sciences, Beijing

2009.09 - 2012.03  Associate Investigator, National Institute of Biological Sciences, Beijing

2012.03 -                Investigator, Institute of Biophysics, Chinese Academy of Sciences, Beijing

2023 - New Cornerstone Investigator

2022 - The 7th VCANBIO Award for Biosciences and Medicine-Achievement Award

2019 - The Second Prize of the State Natural Science Award

2019 - Outstanding Achievement Award of the Chinese Society for Cell Biology

2018 - FVIL Scholar

2013 - The 6th C.C.Tan (Jia-Zhen Tan) Life Science Award

2012 - National Outstanding Young Scientist Award

2012 - HHMI International Early Career Scientist Award

2006 - Lilly-Asian Scientific Excellence Award

Autophagy involves the enclosure of cytoplasmic material in the autophagosome and its subsequent delivery to the lysosome for degradation. The molecular basis of autophagy was first elucidated in yeast, but the autophagy pathway in multicellular organisms is much more complex, containing steps that are absent in yeast. Very little is known about the metazoan-specific mechanisms that underlie the regulation and function of autophagy. The research interest of our lab currently focuses on mechanistic understanding of the autophagic machinery and of the regulation and function of autophagy during development. First, we are using C. elegans as a model to identify essential components for basal autophagy and tissue-specific variants of autophagy. The molecular role of the identified components will be investigated. Second, using degradation of PGL granules during C. elegans embryogenesis as a model, we are studying how protein aggregates are selectively recognized and removed by autophagy. Third, we are investigating how the autophagic machinery integrates signals from other cells and environmental conditions to maintain cell, tissue and organism homeostasis. These studies will provide insights into the molecular mechanism of autophagy and the pathology of various diseases associated with impaired autophagy, such as neurodegeneration.

Research articles

1. Zheng, H., Peng, K.F., Gou, X.M., Ju, C., and Zhang, H. (2023). RNA recruitment switches the fate of protein condensates from autophagic degradation to accumulation. Journal of Cell Biology 222, e202210104.

2. Zheng, Q.X., Chen, Y., Chen, D., Zhao, H.Y., Feng, Y., Meng, Q., Zhao, Y., and Zhang, H. (2022). Calcium transients on the ER surface trigger liquid-liquid phase separation of FIP200 to specify autophagosome initiation sites. Cell 185, 4082-4098.

3. Wang, Z., Chen, D., Guan, D.S., Liang, X.B., Xue, J.F., Zhao, H.Y., Song, G.T., Lou, J.Z., He, Y. and Zhang, H. (2022). Material properties of phase-separated TFEB condensates regulate the autophagy-lysosome pathway. Journal of Cell Biology 221, e202112024.

4. Chen, D., Zheng, Q. X., Sun, L., Ji, M. M., Li, Y., Deng, H. Y., and Zhang, H. (2021). ORF3a of SARS-CoV-2 promotes lysosomal exocytosis-mediated viral egress. Developmental Cell 56, 3250-3263.

5. Liu, N., Zhao, H.Y., Zhao, Y.G., Hu, J.J. and Zhang, H., (2021). The ER membrane proteins Atlastin 2/3 regulate ER targeting of the ULK1 complex and formation of the ER-isolation membrane contact. Journal of Cell Biology 220, e202012091.

6. Miao, G., Zhao, H., Li, Y., Ji, M., Chen, Y., Shi, Y., Bi, Y., Wang, P., Zhang, H. (2021). ORF3a of the COVID-19 virus SARS-CoV-2 blocks HOPS complex-mediated assembly of the SNARE complex required for autolysosome formation, Developmental Cell 56, 427-442.

7. Chen, D., Wang, Z., Zhao, Y.G., Zheng, H., Zhao, H.Y., Liu, N., and Zhang, H. (2020). Inositol polyphosphate multikinase inhibits liquid-liquid phase separation of TFEB to negatively regulate autophagy activity. Developmental Cell 55, 588-602.

8. Miao, G.Y., Zhang, Y.J., Chen, D., and Zhang, H. (2020). The ER-localized transmembrane protein TMEM39A/SUSR2 regulates autophagy by controlling the trafficking of the PtdIns(4)P phosphatase SAC1. Molecular Cell 77, 618-632.

9. Zhang, Y.J., Qi, L.X., and Zhang, H. (2019). TGFβ-like DAF-7 acts as a systemic signal for autophagy regulation in C. elegans. Journal of Cell Biology 218, 3998-4006.

10. Li, D.F., Zhao, G.Y., Li, D., Zhao, H.Y., Huang, J., Miao, G.Y., Feng, D., Liu, P.S., Li, D., and Zhang, H. (2019). The ER-localized protein DFCP1 modulates ER-LD contact formation. Cell Reports 27, 343-358.

11. Zhang, G.M., Wang, Z., Du, Z., and Zhang, H. (2018). mTOR regulates phase separation of PGL granules to modulate their autophagic degradation. Cell 174, 1492-1506.

12. Zhao, Y.G., Liu, N., Miao, G.Y., Chen, Y., Zhao, H.Y, and Zhang, H. (2018). The ER contact proteins VAPA/B interact with multiple autophagy proteins to modulate autophagosome biogenesis. Current Biology 28, 1234-1245.

13. Zhao, G.Y., Chen, Y., Miao, G.Y., Zhao, H.Y., Qu, W.Y., Li, D.F., Wang, Z., Liu, N., Li, L., Chen, S., Liu, P.S., Feng, D., and Zhang, H. (2017). The ER-localized transmembrane protein VMP1 regulates SERCA activity to control ER-isolation membrane contacts for autophagosome formation. Molecular Cell 67, 974-989.

14. Wang, Z., Miao, G.Y., Xue, X., Guo, X.Y., Yuan, C.Z., Wang, Z.Y., Zhang, G.M., Feng, D., Hu, J.J., and Zhang, H. (2016). The Vici syndrome protein EPG5 is a Rab7 effector that determines the fusion specificity of autophagosomes with late endosomes/lysosomes. Molecular Cell 63, 781-795.

15. Wu, F., Watanabe, Y., Guo, X.Y., Qi, X., Wang, P., Zhao, H.Y., Wang, Z., Fujioka, Y., Zhang, H., Ren, J.Q., Fang, T.C., Shen, Y.X., Feng, W., Hu, J.J., Noda, N.N. and Zhang, H. (2015). Structural basis of the differential function of the two C. elegans Atg8 homologs, LGG-1 and LGG-2, in autophagy. Molecular Cell 60, 914-929.

16. Zhao, G.Y., Sun, L., Mia, G.Y., Ji, C.C., Zhao, H.Y., Sun, H.Y., Miao, L., Yoshii, S.R., Mizushima, N., Wang X.Q., and Zhang, H. (2015). The autophagy gene Wdr45/Wipi4 regulates learning and memory function and axonal homeostasis. Autophagy 11, 881-890.

17. Guo, B., Liang, Q.Q., Li, L., Hu, Z., Wu, F., Zhang, P.P., Ma, Y.F., Zhao, B., Kovács, A.L., Zhang, Z.Y., Feng, D., Chen, S., and Zhang, H. (2014). O-GlcNAc-modification of SNAP-29 regulates autophagosome maturation. Nature Cell Biology 16, 1215-1226.

18. Guo, B., Huang, X.X., Zhang, P.P., Qi, L.X., Liang, Q.Q., Zhang, X.B., Huang, J., Fang, B., Hou, W.R., Han, J.H., and Zhang, H. (2014). Genome-wide screen identifies signaling pathways that regulate autophagy during Caenorhabditis elegans development. EMBO reports 15, 705-713.

19. Li, S.H., Yang, P.G., Tian, E, and Zhang, H. (2013). Arginine methylation modulates autophagic degradation of PGL granules in C. elegans. Molecular Cell 52, 421-433.

20. Zhang, P.P., and Zhang, H. (2013). Autophagy modulates miRNA-mediated gene silencing and selectively degrades AIN-1/GW182 in C. elegans. EMBO reports 14, 568-576.

21. Lin, L., Yang, P.G., Huang, X.X., Zhang, H., Lu, Q., and Zhang, H. (2013). The scaffold protein EPG-7 links cargo/receptor complexes with the autophagic assembly machinery. Journal of Cell Biology 201, 113-129.

22. Zhao, H.Y., Zhao, G.Y., Wang, X.W., Xu, L.J., Miao, L., Feng, D., Chen, Q., Kovács, A.L. Fan, D.S., and Zhang, H. (2013). Mice deficient in Epg5 exhibit selective neuronal vulnerability to degeneration. Journal of Cell Biology 200, 731-741.

23. Huang, J., Wang, H.B., Chen, Y.Y. Wang, X.X., and Zhang, H. (2012). Residual body removal during spermatogenesis in C. elegans requires genes that mediate cell corpse clearance. Development 139, 4613-4622.

24. Lu, Q., Yang, P.G., Huang, X.X., Hu, W.Q., Guo, B., Wu, F., Lin, L., Kovács, A.L., Yu, L. and Zhang, H. (2011). The WD40 repeat PtdIns(3)P-binding protein EPG-6 regulates progression of omegasomes to autophagosomes. Developmental Cell 21, 343-357.

25. Huang, X.X., Zhang, H. and Zhang, H. (2011). The zinc-finger protein SEA-2 regulates larval developmental timing and adult life span in C. elegans. Development 138, 2059-2068.

26. Tian, Y., Li, Z.P., Hu, W.Q., Ren, H.Y., Tian, E, Zhao, Y., Lu, Q., Huang, X.X., Yang, P.G., Li, X., Wang, X.C., Kovács, A.L., Yu, L. and Zhang, H. (2010). C. elegans screen identifies autophagy genes specific to multicellular organisms. Cell 141, 1042-1055.

27. Zhang, Y.X., Yan, L.B., Zhou, Z., Yang, P.G., Tian E, Zhang, K., Zhao, Y., Li, Z.P., Song, B., Han, J.H., Miao, L., and Zhang, H. (2009). SEPA-1 mediates the specific recognition and degradation of P granule components by autophagy in C. elegans. Cell 136, 308-321.　

28. Yang, Y., Sun, Y.Y., Luo, X., Zhang, Y.X., Chen, Y.Y., Tian, E, Lints, R., and Zhang, H. (2007). Polycomb-like genes are necessary for specification of dopaminergic and serotonergic neurons in Caenorhabditis elegans. PNAS 104, 852-857.

29. Zhang, T.T., Sun Y.Y., Tian, E, Deng, H.S., Zhang, Y.X., Luo, X., Cai, Q.Q., Wang, H., Chai, J.J., and Zhang, H. (2006). RNA-binding proteins SOP-2 and SOR-1 form a novel PcG-like complex in C. elegans. Development 133, 1023-1033.

Review articles

1. Mayr, C., Mittag,T., Tang, D., Wen, W.Y., Zhang, H., (co-corresponding) and Zhang, H.Y. (2023). Frontiers in biomolecular condensate research. Nature Cell Biology 25, 512-514.

2. Zhang, H. (2022). The genetics of autophagy in multicellular organisms. Annual Review of Genetics. 56, 17-39.

3. Wang, Z., Lou, J.Z., and Zhang, H. (2022). Essence determines phenomenon: Assaying the material properties of biological condensates. Journal of Biological Chemistry 298, 101782.

4. Zhao, Y.G., Codogno, P., and Zhang, H. (2021). Machinery, regulation and pathophysiological implications of autophagosome maturation. Nature Reviews Molecular Cell Biology 22, 733-750.

5. Zhao, Y.G., and Zhang, H. (2020). Phase separation in membrane biology: the interplay between membrane-bound organelles and membraneless condensates. Developmental Cell 55, 30-44.

6. Noda, N.N., Wang, Z., and Zhang, H. (2020). Liquid-liquid phase separation in autophagy. Journal of Cell Biology 219, e202004062.

7. Zhang, H., Ji, X., Li, P.L., Liu, C., Lou, J.Z., Wang, Z., Wen, W.Y., Xiao, Y., Zhang, M.J. and Zhu, X.L. (2020). Liquid-liquid phase separation in biology: mechanisms, physiological functions and human diseases. SCIENCE CHINA Life Sciences 63, 953-985.

8. Zhao, Y.G., and Zhang, H. (2019). Core autophagy genes and human diseases. Current Opinion in Cell Biology 61, 117-125.

9. Wang, Z., and Zhang, H. (2019). Phase separation, transition and autophagic degradation of proteins in development and pathogenesis. Trends in Cell Biology 29, 417-427.

10. Zhao, Y.G., and Zhang, H. (2019). Autophagosome maturation: an epic journey from the ER to lysosomes. Journal of Cell Biology 218, 757-770.

11. Zhao, Y.G., and Zhang, H. (2018). Formation and maturation of autophagosomes in higher eukaryotes: a social network. Current Opinion in Cell Biology 53, 29-36.

12. Joshi, A.S., Zhang, H., and Prinz, W.A. (2017). Organelle biogenesis in the endoplasmic reticulum. Nature Cell Biology 9, 876-882.

13. Zhang, H., and Baehrecke, E.H. (2015). Eaten alive: novel insights into autophagy from multicellular model systems. Trends in Cell Biology 25, 376-387.

14. Yang, P.G., and Zhang, H. (2014). You are what you eat: multifaceted functions of autophagy during C. elegans development. Cell Research 24, 80-91.

(From Hong Zhang, August 28, 2023)