2006年获武汉大学博士学位。2006年至2014年先后在爱尔兰利默里克大学与都柏林圣三一学院从事博士后研究。2014年10月回国工作，现任中科院分子细胞卓越创新中心，中科院上海生化与细胞所课题组长，博士生导师。获2015年上海市“浦江人才计划A类”资助。

　　膜蛋白参与物质转运、信号转导、能量代谢、膜脂合成等基本生命过程，在疾病发生中也起着重要作用。

　　我们实验室主要运用冷冻电镜和X-射线晶体学技术解析膜蛋白的三维结构，阐释其作用机制。重点研究参与脂质(磷脂与固醇)代谢及重要病原微生物侵染过程的蛋白质。研究成果将能够丰富我们对这些生命过程的理解，并为开发具有代谢调控活性和具有医药应用前景的小分子化合物及大分子抗体药物提供结构基础。

1. Hong, J.^# Li, T.^#, Chao, Y.^#, Xu, Y., Zhu, Z., Zhou, Z., Gu, W., Qu, Q.*, Li, D.* Molecular basis of the inositol deacylase PGAP1 involved in quality control of GPI-AP biogenesis. Nat Commun 2024 15:8
2. Yu, S.^#, Zheng, X.^#, Zhou, Y.^#, Gao, Y., Zhou, B., Zhao, Y., Li, T., Li, Y., Mou, J., Cui, X., Yang, Y., Li, D., Chen, M.*, Lavillette, D.*, Meng, G.* Antibody-mediated spike activation promotes cell-cell transmission of SARS-CoV-2. PLoS Pathog 2023 ppat.1011789
3. Xu, Y.^#, Li, T.^#, Zhou, Z.^#, Hong, J., Chao, Y., Zhu, Z., Zhang, Y., Qu, Q.*, Li, D.* Structures of Liganded Glycosylphosphatidylinositol Transamidase Illuminate GPI-AP Biogenesis. Nat Commun 2023 14:5520
4. Li, Y.^#, Peng, J.^#,*, Xia, Y., Pan, C., Li, Y., Gu, W., Wang, J., Wang, C., Wang, Y., Song, J., Zhou, X., Ma, L., Jiang, Y., Liu, B., Feng, Q., Wang, W., Jiao, S., An, L., Li, D., Zhou, Z.*, Zhao, Y.* Sufu limits sepsis-induced lung inflammation via regulating phase separation of TRAF6. Theranostics, 2023, 13 (11):3761-3780
5. Wang X.^#, He, X.^#, Jiang S.^#, Fu, Z.^#, Jiang S., Zhao, X., Zhao, C., Li, Y., Li, D., Zhang, W., Ai, J.*, Zhang, Y.*, Xu, C.*, Wang, P.* Limited enhancement of antibody and B-cell responses to prototype booster vaccination following SARS-CoV-2 Delta breakthrough infection. J Med Virol 2023 2:e28540
6. Lu, M.^#, Zha, J.^#, Zhou, B.^#, Cao, L.^#, Jiang, C., Zhu, Y., Li, T., Lu, L., Zhang, J., Yang, H., Feng, J., Gu, Z., Tang, H., Jiang, L., Li, D.*, Lavillette, D.*, Zhang, X.* A Spike-destructing human antibody effectively neutralizes Omicron-included SARS-CoV-2 variants with therapeutic efficacy. PLoS Pathog 19: e1011085 (2023)
7. Yao, H., Cai, H., Li, D.* Fluorescence-Detection Size-Exclusion Chromatography-Based Thermostability Assay for Membrane Proteins. Methods Mol Biol 2564:299-315 (2023) (book chapter)
8. Yang, Z.^#, Xia, J.^#, Hong, J.^#, Zhang, C., Wei, H., Ying, W., Sun, C., Sun, L., Mao, Y., Gao, Y., Tan, S., Friml J., Li, D., Liu, X.*, Sun, L.* Structural insights into auxin recognition and efflux by Arabidopsis PIN1. Nature 609:611-615 (2022)
9. Xu, Y.^#, Jia, G.^#, Li, T.^#, Zhou, Z.^#, Luo, Y., Cao, Y., Bao, J., Su, Z.*, Qu, Q.* & Li, D.* Molecular insights into biogenesis of glycosylphosphatidylinositol anchor proteins. Nat Commun 13:2617 (2022)
10. Li, T.^#, Zhou, B.^#, Li, Y., Huang, S., Luo, Z., Zhou, Y., Lai, Y., Gautam, A., Bourgeau, S., Wang, S., Bao, J., Tan, J., Lavillette, D.*, Li, D.* Isolation, characterization, and structure-based engineering of a neutralizing nanobody against SARS-CoV-2. Inter J Biol Macromol 209:1379-1388 (2022)
11. Li, T.^#, Zhou, B.^#, Luo, Z.^#, Lai, Y., Huang, S., Zhou, Y., Li, Y., Gautam, A., Bourgeau, S., Wang, S., Bao, J., Tan, J., Lavillette, D.*, Li, D.* Structural characterization of a neutralizing nanobody with broad activity against SARS-CoV-2 variants. Front Microbiol 13:875840 (2022)
12. Luo, Z., Gu, W., Wang, Y., Tang, Y., Li, D.* Selenourea for Experimental Phasing of Membrane Protein Crystals Grown in Lipid Cubic Phase. Crystals 12:976 (2022)
13. Yang, B., Yao, H., Li, D., Liu, Z.* The phosphatidylglycerol phosphate synthase PgsA utilizes a trifurcated amphipathic cavity for catalysis at the membrane-cytosol interface. Curr Res Struct Biol 3:312-323 (2021)
14. Li, T.^#, Cai, H.^#, Zhao, Y.^#, Li, Y.^#, Lai, Y.^#, Yao, H.^#, Liu, DL.^#, Sun, Z.^#, van Vlissingen, MF., Kuiken, T., GeurtsvanKessel, CH., Zhang, N., Zhou, B., Lu, L., Cong, Y., Qin, W., Mondal, M., Duan, B., Xu, S., Richard AS., Raoul, H., Chen, JF., Xu, C., Wu, L., Zhou, H., Huang, Z., Zhang, X., Li, J., Wang, Y., Bi, Y., Rockx., Chen, J.*, Meng, FL.*, Lavillette, D.*, Li, D.* Uncovering a conserved vulnerability site in SARS-CoV-2 by a human antibody. EMBO Mol Med, e14544 (2021)
15. Luo, Y.^#, Wan, G.^#, Zhou, X.^#, Wang, Q., Zhang, Y., Bao, J., Cong, Y., Zhao, Y.*, Li, D.* Architecture of Dispatched, a Transmembrane Protein Responsible for Hedgehog Release. Front Mol Biosci, 8:701826 (2021)
16. Li, T.^#, Cai, H.^#, Yao, H.^#, Zhou, B.^#, Zhang, N.^#, van Vlissingen, MF., Kuiken, T., Han, W., GeurtsvanKessel, CH., Gong, Y., Zhao, Y., Shen, Q., Qin, W., Tian, X., Peng, C., Lai, Y., Wang, Y., Hutter, CAJ., Kuo, S-M., Bao, J., Liu, C., Wang, Y., Richard, AS., Raoul, H., Lan, J., Seeger, MA., Cong, Y., Rockx., Wong, G.*, Bi, Y.*, Lavillette, D.*, Li, D*. A synthetic nanobody targeting RBD protects hamsters from SARS-CoV-2 infection. Nat Commun, 12:4635 (2021)
17. Luo, Y.^#, Wan, G.^#, Zhang, X.^#, Zhou, X.^#, Wang, Q., Fan, J., Cai, H., Ma, L., Wu, H., Qu, Q.*, Cong, Y.*, Zhao, Y.*, Li, D.* Cryo-EM study of Patched in lipid nanodisc suggests a structural basis for its clustering in caveolae. Structure 29: 1286-1294 (2021)
18. Yao, H.^#, Cai, H.^#, Li, T.^#, Zhou, B.^#, Qin, W., Lavillette, D.*, Li, D.* A high-affinity RBD-targeting nanobody improves fusion partner's potency against SARS-CoV-2. PLoS Pathog 17:e1009328 (2021)
19. Zhang L.^#, Yao D.^#, Xia, Y.^#, Zhou, F., Zhang, Q., Wang, Q., Qin, A., Zhao, J., Li, D., Li, Y.*, Zhou, L.*, Cao, Y.* The structural basis for glycerol permeation by human AQP7. Sci Bull 66:1550-1558 (2021)
20. Cai, H.^#, Yao, H.^#, Li, T.^#, Hutter, C.A.J., Li, Y., Tang, Y., Seeger, M.A., Li, D.* An improved fluorescent tag and its nanobodies for membrane protein expression, stability assay, and purification. Commun Biol 3:753 (2020)
21. Yuan, Y. Cao, C. Wen, M. Li, M. Dong, Y. We, L. Wu, J. Cui, T. Li, D.* Chou, J.J.* Ouyang B.* Structural Characterization of the N-Terminal Domain of the Dictyostelium discoideum Mitochondrial Calcium Uniporter. ACS Omega 10.1021/acsomega.9b04045 (2020)
22. Li, D.,* Caffrey, M.* Structure and Functional Characterization of Membrane Integral Proteins in the Lipid Cubic Phase. J Mol Biol 432:5104-5123 (2020) (review)
23. Yao, H^#., Cai, H^#., Li, D*. Thermostabilization of membrane proteins by consensus mutation: a case study for a fungal D8-7 sterol isomerase. J Mol Biol 432:5162-5183 (2020)
24. Cai, H^#. Yao, H^#. Li, T. Tang, Y.,  Li, D*. High-level heterologous expression of the human transmembrane sterol Δ8,Δ7-isomerase in Pichia pastoris. Protein Expr Purif164:105463 (2019)
25. Tang, Y. Li, D*. Developing a High-Throughput Assay for the Integral Membrane Glycerol 3-Phosphate Acyltransferase. Assay Drug Dev Techn 17, 267-274 (2019)
26. Wang, D. Hu, X. Liu, C. Jia, Y. Bai, Y. Cai, C. Qang, Q. Bai, L. Yang, R. Lin, C. Liu, Y. Li, S. Qiao, F. Yao, L. Chen, L. Ge, G. Jiang, H. Li, D. Li, L. Chen, J. Shao, ZM. Zeng, YA. Protein C receptor is a therapeutic stem cell target in a distinct group of breast cancers. Cell Res 29:832-845 (2019)
27. Al-Sahouri, Z., Lee, M-Y., Li, D., Liu, W., Caffrey, M. The Lipid Cubic Phase as a Medium for the Growth of Membrane Protein Microcrystals: A Revolution in Structural Biology. In: Boutet S., Fromme P., Hunter M. (eds) X-ray Free Electron Lasers. Springer, Cham Ch. 4 pp 87-108 (2018) (book chapter)
28. Li, Z^#., Tang, Y^#., Li, D*. In Meso Crystallization of the Integral Membrane Glycerol 3-Phosphate Acyltransferase with Substrates. Cryst Growth Des 18,2243-2258, (2018)
29. Tang Y., Xia H., Li D*. (2018) Membrane Phospholipid Biosynthesis in Bacteria. In: Cao Y. (eds) Advances in Membrane Proteins. Springer, Singapore Ch. 4 pp 77-119 (2018) (book chapter)
30. Li, Z^#., Tang, Y^#., Wu, Y., Zhao S., Bao, J., Luo, Y., Li, D*. Structural insights into the committed step of bacterial phospholipid biosynthesis. Nat Commun 8, 1691(2017).
31. Zha, J. & Li, D^*. Lipid cubic phase for membrane protein X-ray crystallography. In: Wang H., Li G. (eds) Membrane Biophysics. Springer, Singapore Ch. 7, pp 175-220 (2018) (book chapter)
32. Luo, Q., Yang, X., Yu, S., Shi, H., Wang, K., Xiao, L., Zhu, G., Sun, C., Li, T., Li, D., Zhang, X., Zhou, M. & Huang, Y*. Structural basis for lipopolysaccharide extraction by ABC transporter LptB2FG. Nat Struct Mol Biol 24, 469-474, (2017).
33. Bao, Z., Qi, X., Hong, S., Xu, K., He, F., Zhang, M., Chen, J., Chao, D., Zhao, W., Li, D., Wang, J. & Zhang, P*. Structure and mechanism of a group-I cobalt energy coupling factor transporter. Cell Res 27, 675-687, (2017).
34. Zhou, X. E., Gao, X., Barty, A., Kang, Y., He, Y., Liu, W., Ishchenko, A., White, T. A., Yefanov, O., Han, G. W., Xu, Q., de Waal, P. W., Suino-Powell, K. M., Boutet, S., Williams, G. J., Wang, M., Li, D., Caffrey, M., Chapman, H. N., Spence, J. C. H., Fromme, P., Weierstall, U., Stevens, R. C., Cherezov, V., Melcher, K. & Xu, H. E*. X-ray laser diffraction for structure determination of the rhodopsin-arrestin complex. Sci Data 3, 160021, (2016).
35. Prabhu, A., Luu, W., Li, D., Sharpe, L. & J. Brown, A*. DHCR7: A vital enzyme switch between cholesterol and vitamin D production. Prog Lipid Res 64, 138-151, (2016). (review)
36. Olieric, V., Weinert, T., Finke, A. D., Anders, C., Li, D., Olieric, N., Borca, C. N., Steinmetz, M. O., Caffrey, M., Jinek, M. & Wang*, M. Data-collection strategy for challenging native SAD phasing. Acta Crystallogr D 72, 421-429, (2016).
37. Howe, V., Sharpe, L. J., Alexopoulos, S. J., Kunze, S. V., Chua, N. K., Li, D. & Brown, A. J*. Cholesterol homeostasis: How do cells sense sterol excess? Chem Phys Lipids199, 170-178, (2016). (review)
38. Li, D., Stansfeld, P. J., Sansom, M. S. P., Keogh, A., Vogeley, L., Howe, N., Lyons, J. A., Aragao, D., Fromme, P., Fromme, R., Basu, S., Grotjohann, I., Kupitz, C., Rendek, K., Weierstall, U., Zatsepin, N. A., Cherezov, V., Liu, W., Bandaru, S., English, N. J., Gati, C., Barty, A., Yefanov, O., Chapman, H. N., Diederichs, K., Messerschmidt, M., Boutet, S., Williams, G. J., Marvin Seibert, M. & Caffrey, M*. Ternary structure reveals mechanism of a membrane diacylglycerol kinase. Nat Commun 6, 10140, (2015).
39. Li, D., Pye, V. E. & Caffrey, M*. Experimental phasing for structure determination using membrane-protein crystals grown by the lipid cubic phase method. Acta Crystallogr D71, 104-122, (2015).
40. Kang, Y., Zhou, X. E., Gao, X., He, Y., Liu, W., Ishchenko, A., Barty, A., White, T. A., Yefanov, O., Han, G. W., Xu, Q., de Waal, P. W., Ke, J., Eileen Tan, M. H., Zhang, C., Moeller, A., West, G. M., Pascal, B., Van Eps, N., Caro, L. N., Vishnivetskiy, S. A., Lee, R. J., Suino-Powell, K. M., Gu, X., Pal, K., Ma, J., Zhi, X., Boutet, S., Williams, G. J., Messerschmidt, M., Gati, C., Zatsepin, N. A., Wang, D., James, D., Basu, S., Roy-Chowdhury, S., Conrad, C., Coe, J., Liu, H., Lisova, S., Kupitz, C., Grotjohann, I., Fromme, R., Jiang, Y., Tan, M., Yang, H., Li, J., Wang, M., Zheng, Z., Li, D., Howe, N., Zhao, Y., Standfuss, J., Diederichs, K., Dong, Y., Potter, C. S., Carragher, B., Caffrey, M., Jiang, H., Chapman, H. N., Spence, J. C. H., Fromme, P., Weierstall, U., Ernst, O. P., Katritch, V., Gurevich, V. V., Griffin, P. R., Hubbell, W. L., Stevens, R. C., Cherezov, V., Melcher, K. & Xu, H. E*. Crystal structure of rhodopsin bound to arrestin by femtosecond X-ray laser. Nature 523, 561-567, (2015).
41. Weinert, T., Olieric, V., Waltersperger, S., Panepucci, E., Chen, L., Zhang, H., Zhou, D., Rose, J., Ebihara, A., Kuramitsu, S., Li, D., Howe, N., Schnapp, G., Pautsch, A., Bargsten, K., Prota, A. E., Surana, P., Kottur, J., Nair, D. T., Basilico, F., Cecatiello, V., Pasqualato, S., Boland, A., Weichenrieder, O., Wang, B. C., Steinmetz, M. O., Caffrey, M. & Wang, M*. Fast native-SAD phasing for routine macromolecular structure determination. Nat Methods 12, 131-133, (2014).
42. Weierstall, U*., James, D., Wang, C., White, T. A., Wang, D., Liu, W., Spence, J. C., Bruce Doak, R., Nelson, G., Fromme, P., Fromme, R., Grotjohann, I., Kupitz, C., Zatsepin, N. A., Liu, H., Basu, S., Wacker, D., Han, G. W., Katritch, V., Boutet, S., Messerschmidt, M., Williams, G. J., Koglin, J. E., Marvin Seibert, M., Klinker, M., Gati, C., Shoeman, R. L., Barty, A., Chapman, H. N., Kirian, R. A., Beyerlein, K. R., Stevens, R. C., Li, D., Shah, S. T., Howe, N., Caffrey, M. & Cherezov, V*. Lipidic cubic phase injector facilitates membrane protein serial femtosecond crystallography. Nat Commun 5, 3309, (2014).
43. Tan, J^#., Rouse, S. L^#., Li, D^#., Pye, V. E., Vogeley, L., Brinth, A. R., El Arnaout, T., Whitney, J. C., Howell, P. L., Sansom, M. S. & Caffrey, M*. A conformational landscape for alginate secretion across the outer membrane of Pseudomonas aeruginosa. Acta Crystallogr D 70, 2054-2068, (2014).
44. Nji, E., Li, D., Doyle, D. A. & Caffrey, M*. Cloning, expression, purification, crystallization and preliminary X-ray diffraction of a lysine-specific permease from Pseudomonas aeruginosa. Acta Crystallogr F 70, 1362-1367, (2014).
45. Lyons, J. A^#., Parker, J. L^#., Solcan, N., Brinth, A., Li, D., Shah, S. T., Caffrey, M*. & Newstead, S*. Structural basis for polyspecificity in the POT family of proton-coupled oligopeptide transporters. EMBO Rep 15, 886-893, (2014).
46. Li, D., Howe, N., Dukkipati, A., Shah, S. T., Bax, B. D., Edge, C., Bridges, A., Hardwicke, P., Singh, O. M., Giblin, G., Pautsch, A., Pfau, R., Schnapp, G., Wang, M., Olieric, V. & Caffrey, M*. Crystallizing Membrane Proteins in the Lipidic Mesophase. Experience with Human Prostaglandin E2 Synthase 1 and an Evolving Strategy. Cryst Growth Des 14, 2034-2047, (2014).
47. Li, D. & Caffrey, M*. Renaturing membrane proteins in the lipid cubic phase, a nanoporous membrane mimetic. Sci Rep 4, 5806, (2014).
48. Caffrey, M*., Li, D., Howe, N. & Shah, S. T. 'Hit and run' serial femtosecond crystallography of a membrane kinase in the lipid cubic phase. Philos Trans R Soc Lond B Biol Sci369, 20130621, (2014).
49. Caffrey, M*., Eifert, R., Li, D. & Howe, N. The lipid cubic phase or method for crystallizing proteins. Bushings for better manual dispensing. J Appl Crystallogr 47, 1804-1806, (2014).
50. Boland, C^#., Li, D^#., Shah, S. T., Haberstock, S., Dotsch, V., Bernhard, F. & Caffrey, M*. Cell-free expression and in meso crystallisation of an integral membrane kinase for structure determination. Cell Mol Life Sci 71, 4895-4910, (2014).
51. Liu, W., Wacker, D., Gati, C., Han, G. W., James, D., Wang, D., Nelson, G., Weierstall, U., Katritch, V., Barty, A., Zatsepin, N. A., Li, D., Messerschmidt, M., Boutet, S., Williams, G. J., Koglin, J. E., Seibert, M. M., Wang, C., Shah, S. T., Basu, S., Fromme, R., Kupitz, C., Rendek, K. N., Grotjohann, I., Fromme, P., Kirian, R. A., Beyerlein, K. R., White, T. A., Chapman, H. N., Caffrey, M., Spence, J. C., Stevens, R. C. & Cherezov, V*. Serial femtosecond crystallography of G protein-coupled receptors. Science 342, 1521-1524, (2013).
52. Li, D., Shah, S. T. A. & Caffrey, M*. Host Lipid and Temperature as Important Screening Variables for Crystallizing Integral Membrane Proteins in Lipidic Mesophases. Trials with Diacylglycerol Kinase. Cryst Growth Des 13, 2846-2857, (2013).
53. Li, D., Lyons, J. A., Pye, V. E., Vogeley, L., Aragao, D., Kenyon, C. P., Shah, S. T., Doherty, C., Aherne, M. & Caffrey, M*. Crystal structure of the integral membrane diacylglycerol kinase. Nature 497, 521-524, (2013).
54. Hopper, J. T., Yu, Y. T., Li, D., Raymond, A., Bostock, M., Liko, I., Mikhailov, V., Laganowsky, A., Benesch, J. L., Caffrey, M., Nietlispach, D. & Robinson, C. V*. Detergent-free mass spectrometry of membrane protein complexes. Nat Methods 10, 1206-1208, (2013).
55. Caffrey M*, Li, D. Dukkipati, A. Membrane protein structure determination using crystallography and lipidic mesophases: recent advances and successes. Biochemistry51,6266-6288 (2012)
56. Li, D., Boland, C., Walsh, K. & Caffrey, M*. Use of a robot for high-throughput crystallization of membrane proteins in lipidic mesophases. J Vis Exp e4000, (2012).
57. Li, D., Boland, C., Aragao, D., Walsh, K. & Caffrey, M*. Harvesting and cryo-cooling crystals of membrane proteins grown in lipidic mesophases for structure determination by macromolecular crystallography. J Vis Exp e4001, (2012).
58. Nederlof, I., Hosseini, R., Georgieva, D., Luo, J., Li, D. & Abrahams, J. P*. A Straightforward and Robust Method for Introducing Human Hair as a Nucleant into High Throughput Crystallization Trials. Cryst Growth Des 11, 1170-1176, (2011).
59. Li, D., Lee, J. & Caffrey, M*. Crystallizing Membrane Proteins in Lipidic Mesophases. A Host Lipid Screen. Cryst Growth Des 11, 530-537, (2011).
60. Li, D. & Caffrey, M*. Lipid cubic phase as a membrane mimetic for integral membrane protein enzymes. Proc Natl Acad Sci U S A 108, 8639-8644, (2011).