1999-2004 B.S. University of Science and Technology of China
2004-2009 Ph.D. Purdue University, IN, USA
2017-present PI, School of Life Sciences, Peking University
2010-2017 Postdoc, Harvard Medical School
2009-2010 Postdoc, Purdue University
Honors and Awards
2017 Harvard Chinese Life Science YONGJIN Distinguished Research Award
2016 Outstanding Postdoctoral Fellow Award, Harvard Medical School & Harvard School of Dental Medicine
2010 Keystone Symposia Scholarship
2008 H.E. Umbarger Award for the Outstanding Graduate Student in Research, Purdue University
Meeting Organizers and Session Chairs
09/2017 Massachusetts Area Structural Biology Meetings, University of Massachusetts Medical School, Worcester, MA
04/2016 Department of Biological Sciences, Purdue University – Structural Biology Seminar Series
03/2016 Gordon Research Conference - Protein Transport Across Cell Membranes: Mechanism, Structure, and Regulation
The laboratory focuses on transmembrane transport mechanisms of biological macromolecules such as protein and lipid molecules. The communication and regulation of cells and organelles with the outside needs to pass through the cell membranes. Therefore, transmembrane transport of biomacromolecules is a key step for cells to perform various physiological activities. Transmembrane transport is a dynamic, orderly, and tightly regulated process. At the molecular level, the specific interactions of proteins with phospholipid molecules control the transmembrane transport. A range of membrane proteins function as transporters and transport channels to maintain a dynamic balance of transmembrane transport. A large amount of clinical data show that many diseases are caused by mutations in transporters. Therefore, the molecular mechanisms for transmembrane transport will provide a key drug target for the treatment of related diseases. Our laboratory starts with a series of transport channels and transport enzymes, using biochemical and structural biology methods to reveal the cycle and regulation of its molecular transport.
In addition, the laboratory is committed to the development and application of Nanobody technology. Nanobodies are a class of single-chain, single-domain antibodies that are found mainly in Camelidae animals. Compared with traditional antibodies, Nanobodies have the advantages of simple structure, very stable, easy to express and mutation etc. We use the highly specific binding properties of Nanobodies to stabilize the intermediate state of protein complexes, thereby helping to study biochemical and structural biology. We will create a surface display platform to screen and optimize Nanobodies that are widely used in biotechnology and drug development.
Representative Peer-Reviewed Publications
1. Rapoport TA, Li L, and Park E. Annu Rev Cell Dev Biol. 2017; 33:369–390. Structural and Mechanistic Insights into Protein Translocation.
2. Li L*#, Park E*, Ling J, Ingram J, Ploegh H, Rapoport TA#. Nature. 2016 Mar 17;531(7594):395-9. Crystal structure of a substrate-engaged SecY protein-translocation channel. (* equal contribution; # co-corresponding authors)
3. Li L, Fierer JO, Rapoport TA, Howarth M. J Mol Biol. 2014 Jan 23;426(2):309-17. Structural analysis and optimization of the covalent association between SpyCatcher and a peptide Tag.
4. Yun SI, Song BH, Kim JK, Yun GN, Lee EY, Li L, Kuhn RJ, Rossmann MG, Morrey JD, Lee YM. PLoS Pathog. 2014 Jul 31;10(7):e1004290. A molecularly cloned, live-attenuated Japanese encephalitis vaccine SA14-14-2 virus: a conserved single amino acid in the ij Hairpin of the Viral E glycoprotein determines neurovirulence in mice.
5. Wang Z, Li L, Pennington JG, Sheng J, Yap ML, Plevka P, Meng G, Sun L, Jiang W, Rossmann MG. J Virol. 2013 Aug; 87(16):8909-15. Obstruction of Dengue Virus Maturation by Fab Fragments of the 2H2 Antibody.
6. Li L, Jose J, Xiang Y, Kuhn RJ, Rossmann MG. Nature. 2010. Dec 2; 468(7324):705-8. Structural changes of envelope proteins during alphavirus fusion. (Cover image of the issue)
7. Xiang Y, Leiman PG, Li L, Grimes S, Anderson DL, Rossmann MG. Mol Cell. 2009 May 15; 34(3):375-86. Crystallographic insights into the autocatalytic assembly mechanism of a bacteriophage tail spike.
8. Zhou Z, Khaliq M, Suk JE, Patkar C, Li L, Kuhn RJ, Post CB. ACS Chem Biol. 2008 Dec 19; 3(12):765-75. Antiviral compounds discovered by virtual screening of small-molecule libraries against dengue virus E protein.
9. Li L, Lok SM, Yu IM, Zhang Y, Kuhn RJ, Chen J, Rossmann MG. Science. 2008 Mar 28; 319(5871):1830-4. The flavivirus precursor membrane-envelope protein complex: structure and maturation.
10. Yu IM, Zhang W, Holdaway HA, Li L, Kostyuchenko VA, Chipman PR, Kuhn RJ, Rossmann MG, Chen J. Science. 2008 Mar 28;319(5871):1834-7. Structure of the immature dengue virus at low pH primes proteolytic maturation.