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Hong Zhang, Ph.D, Prof., CASM

Principal Investigator
National Laboratory of Biomacromolecules, IBP


Research Interests: Mechanism and regulation of autophagy in multicellular organisms


Email: hongzhang@ibp.ac.cn


Tel: 010-64848238


Address: 15 Datun Road, Chaoyang District, Beijing, 100101, China


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Biography

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

Awards

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

Membership in Academies & Societies

2012 - Associate Editor, Autophagy

2023 - Senior Academic Editor, Journal of Cell Biology

2023 - Editorial Board Member, Cell Chemical Biology

2022 - Editorial Board Member, SCIENCE CHINA Life Sciences

2020 - Editorial Board Member, Trends in Biochemical Sciences

2016 - Editorial Board Member, Cell Death and Differentiation

2016 - Board of Reviewing Editors, eLife

2015 - Editorial Board Member, Journal of Cell Science

2013 - Editorial Board Member, EMBO reports

2010 - Editorial Board Member, Protein & Cell

2021 - Vice Presidents & Secretary General, Biophysical Society of China

Research Interests

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 usingC. elegansas 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 duringC. elegansembryogenesis 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.

Grants
Selected Publications

Research articles

1. Zheng, H., Peng, K.F., Gou, X.M., Ju, C., andZhang, H. (2023). RNA recruitment switches the fate of protein condensates from autophagic degradation to accumulation.Journal of Cell Biology222, e202210104.

2. Zheng, Q.X., Chen, Y., Chen, D., Zhao, H.Y., Feng, Y., Meng, Q., Zhao, Y., andZhang, H.(2022). Calcium transients on the ER surface trigger liquid-liquid phase separation of FIP200 to specify autophagosome initiation sites.Cell185, 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. andZhang, H. (2022). Material properties of phase-separated TFEB condensates regulate the autophagy-lysosome pathway.Journal of Cell Biology221, e202112024.

4. Chen, D., Zheng, Q. X., Sun, L., Ji, M. M., Li, Y., Deng, H. Y., andZhang, H.(2021). ORF3a of SARS-CoV-2 promotes lysosomal exocytosis-mediated viral egress.Developmental Cell56, 3250-3263.

5. Liu, N., Zhao, H.Y., Zhao, Y.G., Hu, J.J. andZhang, 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 Biology220, 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 Cell56, 427-442.

7. Chen, D., Wang, Z., Zhao, Y.G., Zheng, H., Zhao, H.Y., Liu, N., andZhang, H.(2020). Inositol polyphosphate multikinase inhibits liquid-liquid phase separation of TFEB to negatively regulate autophagy activity.Developmental Cell55, 588-602.

8. Miao, G.Y., Zhang, Y.J., Chen, D., andZhang, H. (2020). The ER-localized transmembrane protein TMEM39A/SUSR2 regulates autophagy by controlling the trafficking of the PtdIns(4)P phosphatase SAC1.Molecular Cell77, 618-632.

9. Zhang, Y.J., Qi, L.X., andZhang, H.(2019). TGFβ-like DAF-7 acts as a systemic signal for autophagy regulation inC. elegans.Journal of Cell Biology218, 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., andZhang, H. (2019). The ER-localized protein DFCP1 modulates ER-LD contact formation.Cell Reports27, 343-358.

11. Zhang, G.M., Wang, Z., Du, Z., andZhang, H. (2018). mTOR regulates phase separation of PGL granules to modulate their autophagic degradation.Cell174, 1492-1506.

12. Zhao, Y.G., Liu, N., Miao, G.Y., Chen, Y., Zhao, H.Y, andZhang, H. (2018). The ER contact proteins VAPA/B interact with multiple autophagy proteins to modulate autophagosome biogenesis.Current Biology28, 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., andZhang, H.(2017). The ER-localized transmembrane protein VMP1 regulates SERCA activity to control ER-isolation membrane contacts for autophagosome formation.Molecular Cell67, 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., andZhang, H. (2016). The Vici syndrome protein EPG5 is a Rab7 effector that determines the fusion specificity of autophagosomes with late endosomes/lysosomes.Molecular Cell63, 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. andZhang, H. (2015). Structural basis of the differential function of the twoC. elegansAtg8 homologs, LGG-1 and LGG-2, in autophagy.Molecular Cell60, 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., andZhang, H. (2015). The autophagy geneWdr45/Wipi4regulates learning and memory function and axonal homeostasis.Autophagy11, 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., andZhang, H. (2014). O-GlcNAc-modification of SNAP-29 regulates autophagosome maturation.Nature Cell Biology16, 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., andZhang, H. (2014). Genome-wide screen identifies signaling pathways that regulate autophagy duringCaenorhabditis elegansdevelopment.EMBO reports15, 705-713.

19. Li, S.H., Yang, P.G., Tian, E, andZhang, H. (2013). Arginine methylation modulates autophagic degradation of PGL granules inC. elegans.Molecular Cell52, 421-433.

20. Zhang, P.P., andZhang, H. (2013). Autophagy modulates miRNA-mediated gene silencing and selectively degrades AIN-1/GW182 inC. elegans.EMBO reports14, 568-576.

21. Lin, L., Yang, P.G., Huang, X.X., Zhang, H., Lu, Q., andZhang, H. (2013). The scaffold protein EPG-7 links cargo/receptor complexes with the autophagic assembly machinery.Journal of Cell Biology201, 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., andZhang, H.(2013). Mice deficient in Epg5 exhibit selective neuronal vulnerability to degeneration.Journal of Cell Biology200, 731-741.

23. Huang, J., Wang, H.B., Chen, Y.Y. Wang, X.X., andZhang, H. (2012). Residual body removal during spermatogenesis inC. elegansrequires genes that mediate cell corpse clearance.Development139, 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. andZhang, H. (2011). The WD40 repeat PtdIns(3)P-binding protein EPG-6 regulates progression of omegasomes to autophagosomes.Developmental Cell21, 343-357.

25. Huang, X.X., Zhang, H. andZhang, H. (2011). The zinc-finger protein SEA-2 regulates larval developmental timing and adult life span inC. elegans.Development138, 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. andZhang, H. (2010).C. elegansscreen identifies autophagy genes specific to multicellular organisms.Cell141, 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., andZhang, H. (2009). SEPA-1 mediates the specific recognition and degradation of P granule components by autophagy inC. elegans.Cell136, 308-321. 

28. Yang, Y., Sun, Y.Y., Luo, X., Zhang, Y.X., Chen, Y.Y., Tian, E, Lints, R., andZhang, H. (2007).Polycomb-like genes are necessary for specification of dopaminergic and serotonergic neurons inCaenorhabditis elegans.PNAS104, 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., andZhang, H. (2006). RNA-binding proteins SOP-2 and SOR-1 form a novel PcG-like complex inC. elegans.Development133, 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 Biology25, 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., andZhang, H. (2022). Essence determines phenomenon: Assaying the material properties of biological condensates.Journal of Biological Chemistry298, 101782.

4. Zhao, Y.G., Codogno, P., andZhang, H. (2021). Machinery, regulation and pathophysiological implications of autophagosome maturation.Nature Reviews Molecular Cell Biology22, 733-750.

5. Zhao, Y.G., andZhang, H. (2020). Phase separation in membrane biology: the interplay between membrane-bound organelles and membraneless condensates.Developmental Cell55, 30-44.

6. Noda, N.N., Wang, Z., andZhang, H. (2020). Liquid-liquid phase separation in autophagy.Journal of Cell Biology219, 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 Sciences63, 953-985.

8. Zhao, Y.G., andZhang, H. (2019). Core autophagy genes and human diseases.Current Opinion in Cell Biology61, 117-125.

9. Wang, Z., andZhang, H. (2019). Phase separation, transition and autophagic degradation of proteins in development and pathogenesis.Trends in Cell Biology29, 417-427.

10. Zhao, Y.G., andZhang, H. (2019). Autophagosome maturation: an epic journey from the ER to lysosomes.Journal of Cell Biology218, 757-770.

11. Zhao, Y.G., andZhang, H. (2018). Formation and maturation of autophagosomes in higher eukaryotes: a social network.Current Opinion in Cell Biology53, 29-36.

12. Joshi, A.S.,Zhang, H., and Prinz, W.A. (2017). Organelle biogenesis in the endoplasmic reticulum.Nature Cell Biology9, 876-882.

13.Zhang, H., and Baehrecke, E.H. (2015). Eaten alive: novel insights into autophagy from multicellular model systems.Trends in Cell Biology25, 376-387.

14. Yang, P.G., andZhang, H. (2014). You are what you eat: multifaceted functions of autophagy duringC. elegansdevelopment.Cell Research24, 80-91.

(From Hong Zhang, August 28, 2023)

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Postcode: 100101

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