张明杰 - 复旦大学 - 生物医学研究院

个人简介

Prof. Mingjie Zhang obtained his bachelor’s degree in chemistry from Fudan University, Shanghai in 1988, and his Ph.D. degree in Biochemistry in the University of Calgary, Canada in 1994. After a brief postdoctoral training in the Ontario Cancer Institute, Toronto, Canada, he established his own laboratory as an Assistant Professor in the Department of Biochemistry, Hong Kong University of Science and Technology (HKUST) in 1995. Prof Zhang is currently a Kerry Holdings Professor of Science, Senior Fellow of the Institute for Advanced Study, and Chair Professor in the Division of Life Science, HKUST. He also directs the Center of Systems Biology and Human Health at HKUST. Prof. Zhang’s laboratory has been focusing on structural and biochemical basis of neuronal development and synaptic signaling. In recognition of his research achievements, Prof. Zhang has been recognized by numerous awards including the most prestigious “The State Natural Science Award of China” in 2006. Prof. Zhang was elected to be a member of the Chinese Academy of Science in 2011. He is also a Founding Member of the Academy of Sciences of Hong Kong.

研究领域

Neuronal structural biology is the focus area of our laboratory. We aim to understand the molecular mechanisms governing synaptic signal transduction complex organization, dynamic regulations of synaptic complex assemblies, and trafficking of proteins involved in synaptic signaling using a combination of NMR spectroscopy, X-ray crystallography, biochemistry, molecular biology and cell biology approaches. The second focus of the lab is to elucidate the molecular basis of protein complexes regulating cell polarity establishment and maintenance. In the first area, we are primarily working on synaptic signal transduction complex organizations by various scaffold proteins (e.g. PDZ domain proteins). In postsynaptic neurons, signal transduction complexes are often organized into large multi-components assemblies (transducisomes). The proper organization of such supramolecular complexes is critical for specificity and efficiency of signal transmissions across synapses. We are also interested in the dynamics of various signaling complex assemblies, by investigating regulated protein-protein interactions in synapses. In the second area, we are interested in how protein complexes (e.g. the Par-3/Par-6/aPKC complex and the Usher complex) orchestrate the highly polarized nature of a wide variety of eukaryotic cells including neurons and epithelia. Our prime interest is to understand, from structural and biochemical angles, how these complexes assemble with other cell polarity proteins and lipids in controlling cell polarity. We are also interested in why mutations of polarity proteins are linked with human diseases.

近期论文

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Lv, P., Du, Y., He, C., Zhou, X., Zeng, M., Li, C., Zhang, M., Dong, S., and Chen, X. (2022) "O-GlcNAcylation modulates liquid-liquid phase separation of SynGAP/PSD-95" Nat Chem (in press) Ravi, A., Zeng, M., Chen, C., Sandoval, G., Diaz-Alonso, J., Zhang, M., and Nicoll, R.A (2022) “Long-term potentiation reconstituted with an artificial TARP/PSD-95 complex” Cell Rep (in press). Bai, G. and Zhang, M. (2022) “Inhibitory postsynaptic density from the lens of phase separation” Oxford Open Neurosci (in press) Cinar, H., Oliva, R., Wu, H., and Zhang, M., Chan, H.S., and Winter, R. (2022) “Effects of Cosolvents and Crowding Agents on the Stability and Phase Transition Kinetics of the SynGAP/PSD-95 Condensate Model of Postsynaptic Densities” J Phys Chem B. 126, 1734-1741. Lin, Y.H., Wu, H., Jia, B., Zhang, M., and Chan, H.S. (2022) “Assembly of model postsynaptic densities involves interactions auxiliary to stoichiometric binding” Biophys J 121, 157-171. Vistrup-Parry, M., Chen, X., Johansen, T.L., Bach, S., Buch-Larsen, S.C., Bartling, C.R.O., Ma, C., Clemmensen, L.S., Nielsen, M.L., Zhang, M., and Str?mgaard, K. (2021) “Site-specific phosphorylation of PSD-95 dynamically regulates the postsynaptic density as observed by phase separation” iScience 24, 103268. Unarta, I.C., Xu, J., Shang, Y., Cheung, C.H.P., Zhu, R., Chen, X., Cao, S., Cheung, P.P., Bierer, D., Zhang, M., Huang, X., and Li, X. (2021) “Entropy of stapled peptide inhibitors in free state is the major contributor to the improvement of binding affinity with the GK domain”RSC Chem Biol. 2, 1274-1284. Zhang, H., Lin, L., Liu, J., Pan, L., Lin, Z., Zhang, M., Zhang, J., Cao, Y., Zhu, J., and Zhang, R. (2021) “Phase Separation of MAGI2-Mediated Complex Underlies Formation of Slit Diaphragm Complex in Glomerular Filtration Barrier” J Am Soc Nephrol. 32, 1946-1960. Feng, Z., Jia, B., and Zhang, M.(2021) “Liquid-Liquid Phase Separation in Biology: Specific Stoichiometric Molecular Interactions vs Promiscuous Interactions Mediated by Disordered Sequences”Biochemistry 60, 2397-2406. Feng, Z., Wu, X., and Zhang, M.(2021) "Presynaptic bouton compartmentalization and postsynaptic density-mediated glutamate receptor clustering via phase separation."Neuropharmacology, 108622. Bai G, Zhang, M.(2021). "Clustering acetylcholine receptors in neuromuscular junction by phase-separated Rapsn condensates." Neuron. 109(12):1907-1909. Hosokawa, T., Liu, P. W., Cai, Q., Ferreira, J. S., Levet, F., Butler, C.,Sibarita,J.B., Choquet, D., Groc,L., Hosy,E., Zhang, M. & Hayashi, Y. (2021). "CaMKII activation persistently segregates postsynaptic proteins via liquid phase separation."Nature Neuroscience , 1-9. Wang, X., Ye, F., Wen, Z., Guo, Z., Yu, C., Huang, W. K., Ringeling, F.R.,Su,Y.,Zheng, W.,Zhou, G., Song, H.,Zhang, M., & Ming, G. L. (2019). "Structural interaction between DISC1 and ATF4 underlying transcriptional and synaptic dysregulation in an iPSC model of mental disorders. "Molecular psychiatry, 1-15. Chen, W., Shen, Z., Asteriti, S., Chen, Z., Ye, F., Sun, Z., Wan,J. Montell,C. Hardie, R. Liu, W. & Zhang, M. (2021). "Calmodulin binds to Drosophila TRP with an unexpected mode. " Structure, 29(4), 330-344. Bai, G., Wang, Y., and Zhang, M.(2021) "Gephyrin-mediated formation of inhibitory postsynaptic. density sheet via phase separation " Cell Research, 1-14. Zhou, S., Han, L., Weng, M., Zhu, H., Heng, Y., Wang, G., ... Zhang, M., and Wu, Z.(2021) "Paxbp1 controls a key checkpoint for cell growth and survival during early activation of quiescent muscle satellite cells ." Proceedings of the National Academy of Sciences, 118(13). Zang, J., Ye, F., Solbak, S. M., H?j, L. J., Zhang, M., & Bach, A. (2021). "Identification of novel fragments binding to the PDZ1‐2 domain of PSD‐95. "ChemMedChem, 16(6), 949-954. Hayashi, Y., Ford, L. K., Fioriti, L., McGurk, L., & Zhang, M. (2021)." Liquid-liquid phase separation in physiology and pathophysiology of the nervous system. "Journal of Neuroscience, 41(5), 834-844. Cai, Q., Zeng, M., Wu, X., Wu, H., Zhan, Y., Tian, R., Zhang, M.(2021) "CaMKIIα-driven, phosphatase-checked postsynaptic plasticity via phase separation." Cell Research, 1-15. Ye, J., Zou, G., Zhu, R., Kong, C., Miao, C., Zhang, M., Li,J. Xiong,W.& Wang, C. (2021). "Structural basis of GABARAP-mediated GABA A receptor trafficking and functions on GABAergic synaptic transmission."Nature communications , 12(1), 1-12. Wu, X., Ganzella, M., Zhou, J., Zhu, S., Jahn, R., Zhang, M.(2021) "Vesicle Tethering on the Surface of Phase-Separated Active Zone Condensates." Molecular Cell. Bai, G., & Zhang, M. (2021). "Mesophasic Assembly of Inhibitory Postsynaptic Density. "Neuroscience Bulletin, 37(1), 141-143. Lin, Z., Xie, R., Guan, K., and Zhang, M.(2020) "A WW tandem-mediated dimerization mode of SAV1 essential for Hippo signaling."Cell Reports, 32(10), 108118. Zhu, J., Zhou, Q., Xia, Y., Lin, L., Li, J., Peng, M., Zhang, R., and Zhang, M.(2020) "GIT/PIX condensates are modular and ideal for distinct compartmentalized cell signaling ". Mol Cell, (2020). Wu, X., Cai, Q., Feng, Z., and Zhang, M.(2020) "Liquid-liquid phase separation in neuronal development and synaptic signalling ". Dev Cell, [invited review]. Chen, K., Yang, R., LI, Y., Zhou, J.C., and Zhang, M.(2020) "Giant ankyrin-B suppresses stochastic collateral axon branching via interaction with microtubules ". J Cell Biol 219(8). Li, J., Chen, K., Zhu, R., and Zhang, M.(2020) "Structural basis underlying strong interactions between ankyrins and spectrins ". J Mol Biol, 432, 3838-3850. Wu, X., Cai, Q., Chen, Y., Zhu, S., Mi, J., Wang, J., and Zhang, M.(2020) "Structural basis for the high affinity interaction between CASK and Mint1 ". Structure, 28, 664-673. Zhang, H., Ji, X., Li, P., Liu, C., Lou, J., Wang, Z., Wen, W., Xiao, Y., Zhang, M., Zhu, X.(2020) "Liquid-liquid phase separation in biology: mechanisms, physiological functions and human diseases". Sci China Life Sci, 63, 953-985[invited revirew]. Yu, T., Kuang, H., Chen, J., Lin, X., Wu, Y., Chen, K., Zhang, M., Zhang, W., and Wen, Z. (2020) "Tripartite-motif Family Protein 35-28 Regulates Microglia Development by Preventing Necrotic Death of Microglial Precursors in Zebrafish". J Biol Chem 295.26: 8846-8856. Liu, Z., Yang, Y., Gu, A., Xu, J., Mao, Y., Lu, H., Hu, W., Lei, Q.-Y., Li, Z., Zhang, M., Cai, Y., and Wen, W. .(2020) "Par complex cluster formation mediated by phase separation ". Nat Commun, 11:2266. Cai, Q., Hosokawa, T., Zeng, M., Hayashi, Y., and Zhang, M.(2020) "Shank3 binds to and stabilizes the active form of Rap1 and HRas GTPases via its NTD-ANK tandem with distinct mechanisms ". Structure, 290, 290-300. Ye, J., Li. J., Ye, F., Zhang, Y., Zhang, M., and Wang, C.(2020) "Mechanistic insights into the interactions of dynein regulator Ndel1 with neuronal ankyrins and implications in polarity maintenance ". PNAS, 117, 1207-1215. Chen, X., Wu, X., Wu, H., and Zhang, M.(2020) "Phase separation at the synapse ". Nat Neurosci, 23, 301-310.[invited review] Hong, A.W, Meng, Z., Plouffe, S.W., Lin, Z., Zhang, M., and Guan, K.-L. (2020) "Critical roles of phosphoinositides and NF2 in Hippo pathway regulation ". Gene Dev, 34, 511-525. Cinar, H., Oliva, R., Lin, Y.H., Chen, X., Zhang, M., Chan, H.S., and Winter, R. (2020) "Pressure Sensitivity of SynGAP/PSD-95 Condensates as a Model for Postsynaptic Densities and its Biophysical and Neurological Ramifications ". Chemistry, 26.48: 11024-11031. He, Y., Li, J., and Zhang, M.(2019) "Myosin VII, USH1C and ANKS4B (or USH1G) together form condensed molecular assembly via liquid-liquid phase separation ." Cell Rep, 29, 974-986. Lin, Z., Yang, Z., Xie, R., Ji, Z., Guan, K., and Zhang, M.(2019) "Decoding WW domain tandem-mediated target recognitions in tissue growth and cell polarity ." eLife, 8, e49439. Zeng, M., Díaz-Alonso, J., Ye, F., Chen, X., Xu, J., Ji, Z., Nicoll, RA., and Zhang, M.(2019) "Phase Separation-Mediated TARP/MAGUK Complex Condensation and AMPA Receptor Synaptic Transmission ." Neuron, 104, 1-15. Wang, X., Ye, F., Wen, Z., Guo, Z., Yu, C., ... Song, H., and Zhang, M., Ming, G.(2019) "Structural interaction between DISC1 and ATF4 underlying transcriptional and synaptic dysregulation in an iPSC model of mental disorders ". Molecular Psychiatry, 1-15. Feng, Z., Chen, X., Wu, X., and Zhang, M.(2019) "Formation of biological condensates via phase separation: Characteristics, analytical methods, and physiological implications". Journal of Biological Chemistry, 294.40.14823-14835. Liu, H., Li, Z., Yang, Q., Liu, W., Wan, J., Li, J., and Zhang, M.(2019) "Substrate Docking-mediated Specific and Efficient Lysine Methylation by the SET domain-containing histone methyltransferase SETD7". Journal of Biological Chemistry, 294.36.13355-13365. Li, J., Liu, H., Raval, M., Wan, J., Yengo, C., Liu, W., and Zhang, M.(2019) "Structure of the MORN4/Myo3a Tail Complex Reveals MORN Repeats as Protein Binding Modules". Structure, 27, 1–9. Wang, T., Yan, B., Lou, L., Lin, X., Yu, T., Wu, S., Lu, Q., Liu, W., Huang, Z., Zhang, M. and Wen, Z.(2019) "Nlrc3-like is required for microglia maintenance in zebrafish". Journal of Genetics and Genomics, 46(6), 291–299.. Jin, W., Dai, Y., Li, F., Zhu, L., Huang, Z., Li, J., Zhang, M., Du, J., Zhang, W., and Wen, Z.(2019) "Dysregulation of Microglial Function Contributes to Neuronal Impairment in Mcoln1a-Deficient Zebrafish". iScience, 13, 391–401.. Tao, W., Ma, C., Bemben, M., Li, K., Burlingame, A., Zhang, M. and Nicoll, R.(2019) "Mechanisms underlying the synaptic trafficking of the glutamate delta receptor GluD1". Molecular Psychiatry. Ji, Z., Li, H., Yang, Z., Huang, X., Ke, X., Ma, S., Lin, Z., Lu, Y., and Zhang, M.(2019) "Kibra Modulates Learning and Memory via Binding to Dendrin". Cell Reports, 26, 2064–2077. Wu, X., Cai, Q., Shen, Z., Chen, X., Zeng, M., Du, S., and Zhang, M.(2019) "RIM and RIM-BP Form Presynaptic Active-Zone-like Condensates via Phase Separation". Molecular Cell, 73, 1-14. Li, Z., Liu, H., Li, J., Yang, Q., Feng, Z., Li, Y., Yang, H., Yu, C., Wan, J., Liu, W., and Zhang, M.(2019) "Homer Tetramer Promotes Actin Bundling Activity of Drebrin". Structure, 27(1), 27-38. Feng, Z., Chen, X., Zeng, M., and Zhang, M.(2018) "Phase separation as a mechanism for assembling dynamic postsynaptic density signalling complexes". Current Opinion in Neurobiology, 57, 1-8. Ye, F., Huang, Y., Li, J., Ma, Y., Xie, C., Liu, Z., Deng, X., Wan, J., Xue, T., Liu, W., and Zhang, M.(2018) "An unexpected INAD PDZ tandem-mediated plcβ binding in Drosophila photo receptors". eLife, 7, e41848. Nelson, A. D., Caballero-Florán, R. N., Rodríguez Díaz, J. C., Hull, J. M., Yuan, Y., Chen, K., ..., Wang, C., Zhang, M., Jones, K. S., and Jenkins, P. M.,(2018) "Ankyrin-G regulates forebrain connectivity and network synchronization via interaction with GABARAP". Molecular Psychiatry, 1. Zeng, M., Chen, X., Guan, D., Xu, J., Wu, H., Tong, P., and Zhang, M.(2018) "Reconstituted Postsynaptic Density as a Molecular Platform for Understanding Synapse Formation and Plasticity". Cell, 174, 1-16. Xu, Z., Lo, W., ... and Zhang, M.,..., and Schimmel, P.,(2018) "Bi-allelic Mutations in Phe-tRNA Synthetase Associated with a Multi-system Pulmonary Disease Support Non-translational Function". The American Journal of Human Genetics, 103, 100-114. Li, J., Zhu, R., Chen, K., Zheng, H., Zhao, H., Yuan, C., Zhang, H., Wang, C., and Zhang, M.(2018) "Potent and specific Atg8-targeting autophagy inhibitory peptides from giant ankyrins". Nature Chemical Biology, 14, pages778–787. Wang, Y., Shang, Y., Li, J., Chen, W., Li, G., Wan, J., Liu, W., and Zhang, M.(2018) "Specific Eph receptor-cytoplasmic effector signaling mediated by SAM–SAM domain interactions". eLife, 7, e35677. Feng, Z., Zeng, M., Chen, X., and Zhang, M.(2018) "Neuronal Synapses: Microscale Signal Processing Machineries Formed by Phase Separation?". Biochemistry, 57(17), pp 2530–2539. Shan, Z., Tu, Y., Yang, Y., Liu, Z., Zeng, M., Xu, H., Long, J., Zhang, M., Cai, Y. and Wen, W.(2018) "Basal condensation of Numb and Pon complex via phase transition during Drosophila neuroblast asymmetric division". Nature Communications, 9, 737. Zeng, M., Ye, F., Xu, J., and Zhang, M.(2018) "PDZ Ligand Binding-Induced Conformational Coupling of the PDZ–SH3–GK Tandems in PSD-95 Family MAGUKs". Journal of Molecular Biology, 430(1), 69-86. Zhu, J., Zhou, Q., Shang, Y., Li, H., Peng, M., Ke, X., ... and Zhang, M.(2017) "Synaptic Targeting and Function of SAPAPs Mediated by Phosphorylation-Dependent Binding to PSD-95 MAGUKs". Cell Reports, 21(13), 3781-3793. Ye, F., Kang, E., Yu, C., Qian, X., Jacob, F., Yu, C., ... Song, H., Ming, G., and Zhang, M.(2017) "DISC1 regulates neurogenesis via modulating kinetochore attachment of Ndel1/Nde1 during mitosis". Neuron, 114(41), E8760-E8769. Zhang, L., Jablonski, A. M., Mojsilovic-Petrovic, J., Ding, H., Seeholzer, S., Newton, I. P., ... Shang, Y., Zhang, M., and Kalb, R. G.(2017) "SAP97 Binding Partner CRIPT Promotes Dendrite Growth In Vitro and In Vivo". eNeuro, 4(6), ENEURO-0175. Yao, N., Li, J., Liu, H., Wan, J., Liu, W., and Zhang, M.(2017) "The Structure of the ZMYND8/Drebrin Complex Suggests a Cytoplasmic Sequestering Mechanism of ZMYND8 by Drebrin". Structure, 25(11), 1657-1666. Ma, Q., Ruan, H., Peng, L., Zhang, M., Gack, M. U., and Yao, W. D.(2017) "Proteasome-independent polyubiquitin linkage regulates synapse scaffolding, efficacy, and plasticity". PNAS, 114(41), E8760-E8769. Wen, W., and Zhang, M.(2017) "Protein complex assemblies in epithelial cell polarity and asymmetric cell division". Journal of Molecular Biology. Pedersen, S. W., Albertsen, L., Moran, G. E., Levesque, B., Pedersen, S. B., Bartels, L., Wapenaar, H., Ye, F., Zhang, M., and Bowen, M. E., and Str?mgaard, K.(2017) "Site-Specific Phosphorylation of PSD-95 PDZ Domains Reveals Fine-Tuned Regulation of Protein–Protein Interactions". ACS chemical biology, 12(9), 2313-2323. Ye, F., Zeng, M., and Zhang, M.(2017) "Mechanisms of MAGUK-mediated cellular junctional complex organization". Current Opinion in Structural Biology, 48, 6-15. Chen, K., LI, J., Wang, C., Wei, Z and Zhang, M.(2017) "Autoinhibition of ankyrin-B/G membrane target bindings by intrinsically disordered segments from the tail regions". eLife, 6. Liu, M., Ji, Z., Zhang, M., and Xia, J.(2017) "Versatile site-selective protein reaction guided by WW domain–peptide motif interaction". Bioconjugate chemistry, 28(8), 2199-2205. Zeng, M., Bai, G., and Zhang, M.(2017) "Anchoring high concentrations of SynGAP at postsynaptic densities via liquid-liquid phase separation". Small GTPases (published online on May. 19). Li, J., He, Y., Weck, M. L., Lu, Q., Tyska, M. J., and Zhang, M.(2017) "Structure of Myo7b/USH1C complex suggests a general PDZ domain binding mode by MyTH4-FERM myosins". PNAS 114(19), 3776-2785. Li, J., Chen, Y., Deng, Y., Unarta, I. C., Lu, Q., Huang, X., and Zhang, M.(2017) "Ca2+-Induced Rigidity Change of the Myosin VIIa IQ Motif-Single α Helix Lever Arm Extension". Structure 25, 579–591. Swayne, L. A., Murphy, N. P., Asuri, S., Chen, L., Xu, X., McIntosh, S., Wang, C., ... and Zhang, M., Mohler, P. J., Arbour, L. T.(2017) "Novel Variant in the ANK2 Membrane-Binding Domain Is Associated With Ankyrin-B Syndrome and Structural Heart Disease in a First Nations Population With a High Rate of Long QT Syndrome". Circulation: Cardiovascular Genetics, 10(1), e001537. Zhu, J., Shang, Y., Xia, Y., Zhang, R., and Zhang, M.(2016) "An atypical MAGUK GK target recognition mode revealed by the interaction between DLG and KIF13B". Structure (published online on Sept. 15) doi: 10.1016/j.str.2016.08.008. Zeng, M. Shang, Y., Araki, Y., Guo, T., Huganir, R. L., and Zhang, M.(2016) "Phase transition in postsynaptic densities underlies formation of synaptic complexes and synaptic plasticity". Cell 166, 1163-1175. Zeng, M., Shang, Y., Guo, T., He, Q., Yung, W.-H., Liu, K., and Zhang, M.(2016) "A new binding site outside the canonical PDZ domain determines the specific interaction between Shank and SAPAP and their function in synapses". PNAS 113, E3081-3090. Zhu, J., Shang, Y. and Zhang, M.(2016) "Mechanistic basis of MAGUK-organized complexes in synaptic development and signalling" [invited review]. Nat Rev Neurosci 17,209-223. Zhou, Y., Kaiser, T., Monteiro, P., Zhang, X., Van der Goes, M.S., Wang, D., Barak, B., Zeng, M., Li, C., Lu, C., Wells, M., Amaya, A., Nguyen, S., Lewis, M., Sanjana, N., Zhou, Y., Zhang, M., Zhang, F., Fu, Z., and Feng, G. (2016) "Mice with Shank3 Mutations Associated with ASD and Schizophrenia Display Both Shared and Distinct Defects". Neuron 89,147-162. Li, J., He, Y., Lu, Q., and Zhang, M. (2016) "Mechanistic Basis of Organization of the Harmonin/USH1C-Mediated Brush Border Microvilli Tip-Link Complex". Dev Cell 36, 179-189. Ye, F., Liu, W., Shang, Y. and Zhang, M. 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