Research Summary

Lei Wang received BS and MS from Peking University mentored by Zhongfan Liu, and PhD from UC Berkeley mentored by Peter G. Schultz. His graduate research resulted in the first expansion of the genetic code to include unnatural amino acids (Uaas) in 2001, for which he was awarded the Young Scientist Award by the journal Science. After postdoctoral training with Roger Y. Tsien, Wang started his group at the Salk Institute in 2005, and moved to UCSF in 2014. Wang’s group has developed new methods for the expansion of the genetic code in a variety of cells and model organisms, including mammalian cells, stem cells, C. elegans, and recently embryonic mouse. His group discovered that release factor one (RF1) is nonessential in E. coli, and engineered autonomous bacteria capable of incorporating Uaas at multiple sites with high efficiency. By developing the concept of proximity-enabled bioreactivity, Wang’s group designed and demonstrated that a new class of Uaas, the bioreactive Uaas, can be genetically encoded in live systems. These bioreactive Uaas enable novel covalent bonding abilities to be specifically introduced into proteins and biosystems, opening the door for new protein engineering and biological research in vivo. Wang is a 2006 Beckman Young Investigator, a 2006 Searle Scholar, a 2008 National Institutes of Health Director’s New Innovator Award recipient, and the 2021 Emil Thomas Kaiser Award recipient of the Protein Society.

Education

  • Peking University, Beijing, BS, 1994, Organic Chemistry
  • Peking University, Beijing, MS, 1997, Physical Chemistry
  • University of California, Berkeley, PhD, 2002, Bioorganic Chemistry
  • University of California, San Diego, Postdoctoral, 2005, Molecular Biology & Pharmacology 

Honors & Awards

  • 2002
    Collegiate Inventor, US National Inventors Hall of Fame
  • 2003
    Young Scientist Award - Science, American Association for the Advancement of Science
  • 2003-05
    Merck Fellow, Damon Runyon Cancer Research Foundation
  • 2004
    San Diego BioPharma Award, Sino-American Biotechnology & Pharmaceutical Professional Association and American Chemical Society
  • 2004
    Top Young Innovator, MIT Technology Review TR100
  • 2006
    Beckman Young Investigator, Arnold and Mabel Beckman Foundation
  • 2006
    Searle Scholar, The Chicago Community Trust
  • 2007
    Career Development Award, Ray Thomas Edwards Foundation
  • 2008
    New Faculty Award, California Institute for Regenerative Medicine
  • 2008
    Basil O’Connor Starter Scholar, March of Dimes Foundation
  • 2008
    NIH Director’s New Innovator Award, National Institutes of Health

Selected Publications

  1. Wang N, Wang L. Genetically encoding latent bioreactive amino acids and the development of covalent protein drugs. Curr Opin Chem Biol. 2021 Dec 27; 66:102106.  View on PubMed
  2. Cao L, Wang L. New covalent bonding ability for proteins. Protein Sci. 2021 Nov 11.  View on PubMed
  3. Liu J, Cao L, Klauser PC, Cheng R, Berdan VY, Sun W, Wang N, Ghelichkhani F, Yu B, Rozovsky S, Wang L. A Genetically Encoded Fluorosulfonyloxybenzoyl-l-lysine for Expansive Covalent Bonding of Proteins via SuFEx Chemistry. J Am Chem Soc. 2021 Jul 14; 143(27):10341-10351.  View on PubMed
  4. Cao L, Liu J, Ghelichkhani F, Rozovsky S, Wang L. Genetic Incorporation of ?-N-Benzoyllysine by Engineering Methanomethylophilus alvus Pyrrolysyl-tRNA Synthetase. Chembiochem. 2021 Aug 03; 22(15):2530-2534.  View on PubMed
  5. Berdan VY, Klauser PC, Wang L. Covalent peptides and proteins for therapeutics. Bioorg Med Chem. 2021 01 01; 29:115896.  View on PubMed
  6. Zhou XX, Bracken CJ, Zhang K, Zhou J, Mou Y, Wang L, Cheng Y, Leung KK, Wells JA. Targeting Phosphotyrosine in Native Proteins with Conditional, Bispecific Antibody Traps. J Am Chem Soc. 2020 10 14; 142(41):17703-17713.  View on PubMed
  7. Liu J, Cheng R, Van Eps N, Wang N, Morizumi T, Ou WL, Klauser PC, Rozovsky S, Ernst OP, Wang L. Genetically Encoded Quinone Methides Enabling Rapid, Site-Specific, and Photocontrolled Protein Modification with Amine Reagents. J Am Chem Soc. 2020 10 07; 142(40):17057-17068.  View on PubMed
  8. Li S, Yang B, Kobayashi T, Yu B, Liu J, Wang L. Genetically encoding thyronine for fluorescent detection of peroxynitrite. Bioorg Med Chem. 2020 09 15; 28(18):115665.  View on PubMed
  9. Li Q, Chen Q, Klauser PC, Li M, Zheng F, Wang N, Li X, Zhang Q, Fu X, Wang Q, Xu Y, Wang L. Developing Covalent Protein Drugs via Proximity-Enabled Reactive Therapeutics. Cell. 2020 07 09; 182(1):85-97.e16.  View on PubMed
  10. Wang N, Wang L. Acid-brightening fluorescent protein (abFP) for imaging acidic vesicles and organelles. Methods Enzymol. 2020; 639:167-189.  View on PubMed
  11. Vuong W, Mosquera-Guagua F, Sanichar R, McDonald TR, Ernst OP, Wang L, Vederas JC. Synthesis of Chiral Spin-Labeled Amino Acids. Org Lett. 2019 12 20; 21(24):10149-10153.  View on PubMed
  12. Liu J, Cai L, Sun W, Cheng R, Wang N, Jin L, Rozovsky S, Seiple IB, Wang L. Photocaged Quinone Methide Crosslinkers for Light-Controlled Chemical Crosslinking of Protein-Protein and Protein-DNA Complexes. Angew Chem Int Ed Engl. 2019 12 19; 58(52):18839-18843.  View on PubMed
  13. Liu J, Li S, Aslam NA, Zheng F, Yang B, Cheng R, Wang N, Rozovsky S, Wang PG, Wang Q, Wang L. Genetically Encoding Photocaged Quinone Methide to Multitarget Protein Residues Covalently in Vivo. J Am Chem Soc. 2019 06 19; 141(24):9458-9462.  View on PubMed
  14. Yang B, Wang N, Schnier PD, Zheng F, Zhu H, Polizzi NF, Ittuveetil A, Saikam V, DeGrado WF, Wang Q, Wang PG, Wang L. Genetically Introducing Biochemically Reactive Amino Acids Dehydroalanine and Dehydrobutyrine in Proteins. J Am Chem Soc. 2019 05 15; 141(19):7698-7703.  View on PubMed
  15. Hoppmann C, Wang L. Genetically encoding photoswitchable click amino acids for general optical control of conformation and function of proteins. Methods Enzymol. 2019; 624:249-264.  View on PubMed
  16. Yang B, Wu H, Schnier PD, Liu Y, Liu J, Wang N, DeGrado WF, Wang L. Proximity-enhanced SuFEx chemical cross-linker for specific and multitargeting cross-linking mass spectrometry. Proc Natl Acad Sci U S A. 2018 10 30; 115(44):11162-11167.  View on PubMed
  17. Liu J, Cheng R, Wu H, Li S, Wang PG, DeGrado WF, Rozovsky S, Wang L. Building and Breaking Bonds via a Compact S-Propargyl-Cysteine to Chemically Control Enzymes and Modify Proteins. Angew Chem Int Ed Engl. 2018 09 24; 57(39):12702-12706.  View on PubMed
  18. Fu C, Kobayashi T, Wang N, Hoppmann C, Yang B, Irannejad R, Wang L. Genetically Encoding Quinoline Reverses Chromophore Charge and Enables Fluorescent Protein Brightening in Acidic Vesicles. J Am Chem Soc. 2018 09 05; 140(35):11058-11066.  View on PubMed
  19. Liu J, Zheng F, Cheng R, Li S, Rozovsky S, Wang Q, Wang L. Site-Specific Incorporation of Selenocysteine Using an Expanded Genetic Code and Palladium-Mediated Chemical Deprotection. J Am Chem Soc. 2018 07 18; 140(28):8807-8816.  View on PubMed
  20. Wang N, Yang B, Fu C, Zhu H, Zheng F, Kobayashi T, Liu J, Li S, Ma C, Wang PG, Wang Q, Wang L. Genetically Encoding Fluorosulfate-l-tyrosine To React with Lysine, Histidine, and Tyrosine via SuFEx in Proteins in Vivo. J Am Chem Soc. 2018 04 18; 140(15):4995-4999.  View on PubMed

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