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Members of CAS, CAE
National Outstanding Young Scientists Award
Principal Investigators
Address: 320 Yue Yang Road, Shanghai 200031, P.R. China
Tel: 86-21-54920000
Fax: 86-21-54921011
Email: sibcb@sibs.ac.cn
Website: www.sibcb.ac.cn
Principal Investigators
LI Dianfan
Ph.D., Professor
Shanghai Institute for Biological Sciences, Chinese Academy of Science, 333 Haike Road, Pudong, Shanghai, China.
Email: dianfan.li@@sibcb.ac.cn

Research Areas
Protein Sciences; Membrane Protein Structure Biology

Research Interests

Membrane proteins perform a wide variety of fundamental physiological functions of cells. Nearly a third of genomes encode membrane proteins, and they account for 60% of approved drug targets. By sharp contrast, membrane protein structures only account for less than 2% of total known structures. This reflects the challenges in membrane protein structure study.
Research in my lab focuses on the structure and function of membrane proteins with significant physiological importance and pharmaceutical relevance, such as those involved in lipid metabolism. We also devote substantial efforts to develop techniques for the purification and crystallization of membrane proteins. They include protein engineering, antibody selection, and lipid cubic phase crystallization.

Selected Publications

(*corresponding author; #co-first author) ORCID 0000-0003-4729-4678
  1. 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 (2020)
  2. 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)
  3. Li, D.*, Caffrey, M.* Structure and Functional Characterization of Membrane Integral Proteins in the Lipid Cubic Phase.  J Mol Biol  10.1016/j.jmb.2020.02.024 (2020)
  4. Cai, H#. Yao, H#. Li, T. Tang, Y. & Li, D*. High-level heterologous expression of the human transmembrane sterol ¦¤8,¦¤7-isomerase in Pichia pastoris. Protein Expr Purif 164:105460 (2019)
  5. 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)
  6. 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)
  7. Li, Z#., Tang, Y#. & Li, D*. In Meso Crystallization of the Integral Membrane Glycerol 3-phosphate Acyltransferase with Substrates. Cryst Growth Des 2018 DOI: 10.1021/acs.cgd.7b01678
  8. 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)
  9. 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 2017 8:1691.
  10. Zha, J. & Li, D*. Lipid cubic phase for membrane protein X-ray crystallography. in Membrane Biophysics. Springer, Ch. 7 pp 175-220  (2018).
  11. 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)
  12. 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).
  13. 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).
  14. 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).
  15. 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).
  16. 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 Lipids 199, 170-178, (2016).
  17. 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).
  18. Y Kang, X. E. Zhou, X. Gao, Y. He, W. Liu, A Ishchenko, A Barty, T. A. White, O. Yefanov, G. W. Han, Q. Xu, P. W. de Waa, J. Ke, M. H. Tan, C. Zhang, A. Moeller, G. M. West, B. D. Pascal, N. Van Eps, L. N. Caro, S. A. Vishnivetskiy, R. J. Lee, K. M. Suino-Powell, X. Gu, K. Pal, J. Ma, X. Zhi, S. Boutet, G. J. Williams, M. Messerschmidt, C. Gati, N. A. Zatsepin, D. Wang, D. James, S. Basu, S. Roy-Chowdhury, C. E. Conrad, J. Coe, H. Liu, S. Lisova, C. Kupitz, I. Grotjohann, R. Fromme, Y. Jiang, M. Tan, H. Yang, J. Li, M. Wang, Z. Zheng, D. Li, N. Howe, Y. Zhao, J. Standfuss, K. Diederichs, Y. Dong, C. S. Potter, B. Carragher, M. Caffrey, H. Jiang, H. N. Chapman, J. C. Spence, P. Fromme, U. Weierstall, O. P. Ernst, V. Katritch, V. V. Gurevich, P. R. Griffin, W. L. Hubbell, R. C. Stevens, V. Cherezov, K. Melcher, H. E. Xu. Crystal structure of rhodopsin bound to arrestin by femtosecond X-ray laser. Nature 2015 523:561-7
  19. D Li, P. J. Stansfeld, M. S. P. Sansom, A. Keogh, L. Vogeley, N. Howe, J. A. Lyons, D. Aragao, P. Fromme, R. Fromme, S. Basu, I. Grotjohann, C. Kupitz, K. Rendek, U. Weierstall, N. A. Zatsepin, V. Cherezov, W. Liu, S. Bandaru, N. J. English, C. Gati1, A. Barty, O. Yefanov, H. Chapman, K. Diederichs, M. Messerschmidt S. Boutet, G. J. Williams, M. M. Seibert, M. Caffrey. Ternary structure reveals mechanism of a membrane diacylglycerol kinase. Nat Commun. 2015 6:10140
  20. D Li, VE Pye, M Caffrey. Experimental phasing for structure determination using membrane protein crystals grown by the lipid cubic phase method. Acta Crystallogr. D.  2015 71:104-22
  21. T Weinert, V Olieric, S Waltersperger, E Panepucci, L Chen, H Zhang,  D Zhou, J Rose, A Ebihara, S Kuramitsu,  D Li, N Howe, G Schnapp, A Pautsch, K Bargsten, AE Prota, P Surana, J Kottur, DT Nair, F Basilico, V Cecatiello, S Pasqualato, A Boland, O Weichenrieder, B Wang, MO Steinmetz, M Caffrey, M Wang. Fast native-SAD phasing for routine macromolecular structure determination. Nat. Methods.  2015 12 : 131-3
  22. D Li, N Howe, A Dukkipati, STA Shah, BD Bax, C Edge, A Bridges, P Hardwick, OMP Singh, A Pautsch, R Pfau, G Schnapp, M Wang, V Olieric, M Caffrey. Crystallizing membrane proteins in the lipidic mesophase. Experience with human prostaglandin E2 synthase 1 and an evolving strategy.  Cryst. Growth Des. 2014 14:2037-2047
  23. D Li, M Caffrey. Renaturing Membrane Proteins in the Lipid Cubic Phase, a Nanoporous Membrane Mimetic. Sci. Rep. 2014 4:5806
  24. C Boland, D Li* (co-first author), STA Shah, S Haberstock, V Dötsch, F Bernhard, M Caffrey. Cell-free expression and in meso crystallisation of an integral membrane kinase for structure determination. Cell. Mol. Life Sci. 2014 71:4895-4910
  25. J Tan*, SL Rouse*, D Li* (co-first author), VE Pye, L Vogeley, A Brinth, T El Arnaout, JC Whitney, PL Howell, MSP Sansom, M Caffrey. A conformational landscape for alginate secretion across the outer membrane of Pseudomonas aeruginosa. Acta Crystallogr. D. 2014. 70:2054-2068.
  26. U Weierstall, D James, D Wang, W Liu, JCH Spence, RB Doak, G Nelson, P Fromme, R Fromme, I Grotjohann, C Kupitz, NA Zatsepin, S Basu, D Wacker, C Wang, S Boutet, M Messerschmidt, GJ Williams, JE Koglin, MM Seibert, C Gati, RL Shoeman, A Barty, HN Chapman, RA Kirian, KR Beyerlein, RC Stevens, D Li, STA Shah, N Howe, M Caffrey, V Cherezov. Lipidic cubic phase injector facilitates membrane protein serial femtosecond crystallography. Nat. Commun. 2014. 5: 3309
  27. JA Lyons, JL Parker, N Solcan, A Brinth, D Li, S.T.A. Shah, M Caffrey, S Newstead. Structural basis for polyspecificity in the POT family of proton coupled oligopeptide transporters. EMBO Rep. 2014 15:886-93
  28. M Caffrey, D Li, N Howe, STA Shah. 'Hit and run¡¯ serial femtosecond crystallography of a membrane kinase in the lipid cubic phase.  Phil. Trans. R. Soc. B. 2014. 369:20130621
  29. M Caffrey, R Eifert, D Li, N Howe. The lipid cubic phase or in meso method for crystallizing proteins.  Bushings for better manual dispensing. J. Appl. Crystallogr. 2014 16:1804-1806
  30. E Nji, D Li, DA Doyle, M Caffrey. Cloning, expression, purification, crystallization and preliminary X-ray diffraction of a lysine-specific permease from Pseudomonas aeruginosa. Acta. Crystallogr. F 2014 70 : 1362-7
  31. D Li, JA Lyons, VE Pye, L Vogeley, D Aragao, C Kenyon, ST Shah, C Doherty, M Aherne, M Caffrey. Crystal structure of the integral membrane diacylglycerol kinase. Nature 2013 497:521-4.
  32. D Li, ST Shah, M Caffrey. Host lipid and temperature as important screening variables for crystallizing integral membrane proteins in lipidic mesophases. Trials with diacylglycerol kinase. Cryst. Growth Des. 2013 13:2846-57.
  33. W Liu, D Wacker, C Gati, GW Han, D James, D Wang, G Nelson, U Weierstall, V Katritch, A Barty, NA Zatsepin, D Li, M Messerschmidt, S Boutet, GJ Williams, JE Koglin, MM Seibert, C Wang, ST Shah, S Basu, R Fromme, C Kupitz, KN Rendek, I Grotjohann, P Fromme, RA Kirian, KR Beyerlein, TA White, HN Chapman, M Caffrey, JC Spence, RC Stevens, V Cherezov. Serial femtosecond crystallography of G protein-coupled receptors. Science 2013 342:1521-4
  34. JT Hopper, YT Yu, D Li, A Raymond, M Bostock, I Liko, V Mikhailov, A Laganowsky, JL Benesch, M Caffrey, D Nietlispach, CV Robinson. Detergent-free mass spectrometry of membrane protein complexes. Nat. Methods 2013 10: 1206-8
  35. M Caffrey, D Li, A Dukkipati. Membrane protein structure determination using crystallography and lipidic mesophases: Recent advances and successes. Biochemistry 2012 51:6266-88.
  36. 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).
  37. 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).
  38. D Li, M Caffrey. Lipid cubic phase as a membrane mimetic for integral membrane protein enzymes. Proc. Natl. Acad. Sci. USA 2011 108:8639-44. 
  39. D Li, J Lee, M Caffrey. Crystallizing membrane proteins in lipidic mesophases. A host lipid screen. Cryst. Growth Des. 2011 11:530-7. 
  40. Nederlof, I., Hosseini, R., Georgieva, D., Luo, J., D Li,. & 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).

Education Background & Academic Experience

2014 ¨C present Professor, National Center for Protein Sciences, Institute of Biochemistry and Cell Biology, Shanghai Institute for Biological Sciences, Chinese Academy of Science, Shanghai, China.
2011-2014, Research Fellow, School of Medicine and School of Biochemistry and Immunology, Trinity College Dublin, Dublin, Ireland.
2006-2011, Postdoctoral Research Fellow, Department of Chemical and Engineer Sciences, University of Limerick, Limerick, Ireland.
2008, J1 Exchange Scholar, The Scripps Research Institute, La Jolla, CA, USA.
2002-2006, Ph.D in Molecular Biology, School of Life Sciences, Wuhan University, Wuhan, China.
1999-2002, M.Sc. in Pomology, Department of Plant Science and Technology, Hunan Agricultural University, Changsha, China.
1995-1999, B.Sc. in Horticulture, Hunan Agricultural University, Changsha, China.


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