Lei Wang, PhD
Professor
Pharmaceutical Chemistry
School of Pharmacy

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.

• The proximity-enabled sulfur fluoride exchange reaction in the protein context.
  Chemical science 2023 Yu B, Cao L, Li S, Klauser PC, Wang L
• Covalent Proteins as Targeted Radionuclide Therapies Enhance Antitumor Effects.
  ACS central science 2023 Klauser PC, Chopra S, Cao L, Bobba KN, Yu B, Seo Y, Chan E, Flavell RR, Evans MJ, Wang L
• Residue selective crosslinking of proteins through photoactivatable or proximity-enabled reactivity.
  Current opinion in chemical biology 2023 Liu J, Yang B, Wang L
• Encoding latent SuFEx reactive meta-fluorosulfate tyrosine to expand covalent bonding of proteins.
  Chemical communications (Cambridge, England) 2022 Klauser PC, Berdan VY, Cao L, Wang L
• Accelerating PERx Reaction Enables Covalent Nanobodies for Potent Neutralization of SARS-Cov-2 and Variants.
  bioRxiv : the preprint server for biology 2022 Yu B, Li S, Tabata T, Wang N, Kumar GR, Liu J, Ott MM, Wang L
• Genetically encoding latent bioreactive amino acids and the development of covalent protein drugs.
  Current opinion in chemical biology 2021 Wang N, Wang L
• A Genetically Encoded Fluorosulfonyloxybenzoyl-l-lysine for Expansive Covalent Bonding of Proteins via SuFEx Chemistry.
  Journal of the American Chemical Society 2021 Liu J, Cao L, Klauser PC, Cheng R, Berdan VY, Sun W, Wang N, Ghelichkhani F, Yu B, Rozovsky S, Wang L
• Genetic Incorporation of ϵ-N-Benzoyllysine by Engineering Methanomethylophilus alvus Pyrrolysyl-tRNA Synthetase.
  Chembiochem : a European journal of chemical biology 2021 Cao L, Liu J, Ghelichkhani F, Rozovsky S, Wang L
• Covalent peptides and proteins for therapeutics.
  Bioorganic & medicinal chemistry 2020 Berdan VY, Klauser PC, Wang L
• Targeting Phosphotyrosine in Native Proteins with Conditional, Bispecific Antibody Traps.
  Journal of the American Chemical Society 2020 Zhou XX, Bracken CJ, Zhang K, Zhou J, Mou Y, Wang L, Cheng Y, Leung KK, Wells JA
• Genetically Encoded Quinone Methides Enabling Rapid, Site-Specific, and Photocontrolled Protein Modification with Amine Reagents.
  Journal of the American Chemical Society 2020 Liu J, Cheng R, Van Eps N, Wang N, Morizumi T, Ou WL, Klauser PC, Rozovsky S, Ernst OP, Wang L
• Genetically encoding thyronine for fluorescent detection of peroxynitrite.
  Bioorganic & medicinal chemistry 2020 Li S, Yang B, Kobayashi T, Yu B, Liu J, Wang L
• Developing Covalent Protein Drugs via Proximity-Enabled Reactive Therapeutics.
  Cell 2020 Li Q, Chen Q, Klauser PC, Li M, Zheng F, Wang N, Li X, Zhang Q, Fu X, Wang Q, Xu Y, Wang L
• Acid-brightening fluorescent protein (abFP) for imaging acidic vesicles and organelles.
  Methods in enzymology 2020 Wang N, Wang L
• Synthesis of Chiral Spin-Labeled Amino Acids.
  Organic letters 2019 Vuong W, Mosquera-Guagua F, Sanichar R, McDonald TR, Ernst OP, Wang L, Vederas JC
• Photocaged Quinone Methide Crosslinkers for Light-Controlled Chemical Crosslinking of Protein-Protein and Protein-DNA Complexes.
  Angewandte Chemie (International ed. in English) 2019 Liu J, Cai L, Sun W, Cheng R, Wang N, Jin L, Rozovsky S, Seiple IB, Wang L
• Genetically Encoding Photocaged Quinone Methide to Multitarget Protein Residues Covalently in Vivo.
  Journal of the American Chemical Society 2019 Liu J, Li S, Aslam NA, Zheng F, Yang B, Cheng R, Wang N, Rozovsky S, Wang PG, Wang Q, Wang L
• Genetically Introducing Biochemically Reactive Amino Acids Dehydroalanine and Dehydrobutyrine in Proteins.
  Journal of the American Chemical Society 2019 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 encoding photoswitchable click amino acids for general optical control of conformation and function of proteins.
  Methods in enzymology 2019 Hoppmann C, Wang L
• Proximity-enhanced SuFEx chemical cross-linker for specific and multitargeting cross-linking mass spectrometry.
  Proceedings of the National Academy of Sciences of the United States of America 2018 Yang B, Wu H, Schnier PD, Liu Y, Liu J, Wang N, DeGrado WF, Wang L
• Building and Breaking Bonds via a Compact S-Propargyl-Cysteine to Chemically Control Enzymes and Modify Proteins.
  Angewandte Chemie (International ed. in English) 2018 Liu J, Cheng R, Wu H, Li S, Wang PG, DeGrado WF, Rozovsky S, Wang L
• Genetically Encoding Quinoline Reverses Chromophore Charge and Enables Fluorescent Protein Brightening in Acidic Vesicles.
  Journal of the American Chemical Society 2018 Fu C, Kobayashi T, Wang N, Hoppmann C, Yang B, Irannejad R, Wang L
• Site-Specific Incorporation of Selenocysteine Using an Expanded Genetic Code and Palladium-Mediated Chemical Deprotection.
  Journal of the American Chemical Society 2018 Liu J, Zheng F, Cheng R, Li S, Rozovsky S, Wang Q, Wang L
• Genetically Encoding Fluorosulfate-l-tyrosine To React with Lysine, Histidine, and Tyrosine via SuFEx in Proteins in Vivo.
  Journal of the American Chemical Society 2018 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 Unnatural Amino Acids in Neurons In Vitro and in the Embryonic Mouse Brain for Optical Control of Neuronal Proteins.
  Methods in molecular biology (Clifton, N.J.) 2018 Kang JY, Kawaguchi D, Wang L
• Spontaneous and specific chemical cross-linking in live cells to capture and identify protein interactions.
  Nature communications 2017 Yang B, Tang S, Ma C, Li ST, Shao GC, Dang B, DeGrado WF, Dong MQ, Wang PG, Ding S, Wang L
• Optocontrol of glutamate receptor activity by single side-chain photoisomerization.
  eLife 2017 Klippenstein V, Hoppmann C, Ye S, Wang L, Paoletti P
• Heritable expansion of the genetic code in mouse and zebrafish.
  Cell research 2016 Chen Y, Ma J, Lu W, Tian M, Thauvin M, Yuan C, Volovitch M, Wang Q, Holst J, Liu M, Vriz S, Ye S, Wang L, Li D
• Using Protein-Confined Proximity To Determine Chemical Reactivity.
  Journal of the American Chemical Society 2016 Kobayashi T, Hoppmann C, Yang B, Wang L
• Editorial overview: Chemistry for biopolymers to investigate and even move beyond nature.
  Current opinion in chemical biology 2016 Pentelute BL, Wang L
• Cysteine Sulfoxidation Increases the Photostability of Red Fluorescent Proteins.
  ACS chemical biology 2016 Ren H, Yang B, Ma C, Hu YS, Wang PG, Wang L
• Development of background-free tame fluorescent probes for intracellular live cell imaging.
  Nature communications 2016 Alamudi SH, Satapathy R, Kim J, Su D, Ren H, Das R, Hu L, Alvarado-Martínez E, Lee JY, Hoppmann C, Peña-Cabrera E, Ha HH, Park HS, Wang L, Chang YT
• Optical Control of a Neuronal Protein Using a Genetically Encoded Unnatural Amino Acid in Neurons.
  Journal of visualized experiments : JoVE 2016 Kang JY, Kawaguchi D, Wang L
• Proximity-enabled bioreactivity to generate covalent peptide inhibitors of p53-Mdm4.
  Chemical communications (Cambridge, England) 2016 Hoppmann C, Wang L
• In Situ Formation of an Azo Bridge on Proteins Controllable by Visible Light.
  Journal of the American Chemical Society 2015 Hoppmann C, Maslennikov I, Choe S, Wang L
• A versatile platform to analyze low-affinity and transient protein-protein interactions in living cells in real time.
  Cell reports 2014 Li YC, Rodewald LW, Hoppmann C, Wong ET, Lebreton S, Safar P, Patek M, Wang L, Wertman KF, Wahl GM
• Genetically encoding an electrophilic amino acid for protein stapling and covalent binding to native receptors.
  ACS chemical biology 2014 Chen XH, Xiang Z, Hu YS, Lacey VK, Cang H, Wang L
• Response and adaptation of Escherichia coli to suppression of the amber stop codon.
  Chembiochem : a European journal of chemical biology 2014 Wang Q, Sun T, Xu J, Shen Z, Briggs SP, Zhou D, Wang L
• Genetically encoding photoswitchable click amino acids in Escherichia coli and mammalian cells.
  Angewandte Chemie (International ed. in English) 2014 Hoppmann C, Lacey VK, Louie GV, Wei J, Noel JP, Wang L
• Proximity-enabled protein crosslinking through genetically encoding haloalkane unnatural amino acids.
  Angewandte Chemie (International ed. in English) 2014 Xiang Z, Lacey VK, Ren H, Xu J, Burban DJ, Jennings PA, Wang L
• Expanding the library and substrate diversity of the pyrrolysyl-tRNA synthetase to incorporate unnatural amino acids containing conjugated rings.
  Chembiochem : a European journal of chemical biology 2013 Lacey VK, Louie GV, Noel JP, Wang L
• Expression of fluorescent cyclotides using protein trans-splicing for easy monitoring of cyclotide-protein interactions.
  Angewandte Chemie (International ed. in English) 2013 Jagadish K, Borra R, Lacey V, Majumder S, Shekhtman A, Wang L, Camarero JA
• Release factor one is nonessential in Escherichia coli.
  ACS chemical biology 2012 Johnson DB, Wang C, Xu J, Schultz MD, Schmitz RJ, Ecker JR, Wang L
• Expanding the genetic code of Caenorhabditis elegans using bacterial aminoacyl-tRNA synthetase/tRNA pairs.
  ACS chemical biology 2012 Parrish AR, She X, Xiang Z, Coin I, Shen Z, Briggs SP, Dillin A, Wang L
• Genetic incorporation of unnatural amino acids into proteins in yeast.
  Methods in molecular biology (Clifton, N.J.) 2012 Wang Q, Wang L
• Genetically encoding unnatural amino acids in neural stem cells and optically reporting voltage-sensitive domain changes in differentiated neurons.
  Stem cells (Dayton, Ohio) 2011 Shen B, Xiang Z, Miller B, Louie G, Wang W, Noel JP, Gage FH, Wang L
• A fluorescent reporter of the phosphorylation status of the substrate protein STAT3.
  Angewandte Chemie (International ed. in English) 2011 Lacey VK, Parrish AR, Han S, Shen Z, Briggs SP, Ma Y, Wang L
• Photo-cross-linkers incorporated into G-protein-coupled receptors in mammalian cells: a ligand comparison.
  Angewandte Chemie (International ed. in English) 2011 Coin I, Perrin MH, Vale WW, Wang L
• Enantiospecific synthesis of genetically encodable fluorescent unnatural amino acid L-3-(6-acetylnaphthalen-2-ylamino)-2-aminopropanoic acid.
  The Journal of organic chemistry 2011 Xiang Z, Wang L
• Stereochemical basis for engineered pyrrolysyl-tRNA synthetase and the efficient in vivo incorporation of structurally divergent non-native amino acids.
  ACS chemical biology 2011 Takimoto JK, Dellas N, Noel JP, Wang L
• Genetic Incorporation of Unnatural Amino Acids into Proteins
  Comprehensive Natural Products Chemistry II Chemistry and Biology 2010 Parrish AR, Wang L
• Esterification of an unnatural amino acid structurally deviating from canonical amino acids promotes its uptake and incorporation into proteins in mammalian cells.
  Chembiochem : a European journal of chemical biology 2010 Takimoto JK, Xiang Z, Kang JY, Wang L
• Imprints of the genetic code in the ribosome.
  Proceedings of the National Academy of Sciences of the United States of America 2010 Johnson DB, Wang L
• Impact of nonnatural amino acid mutagenesis on the in vivo function and binding modes of a transcriptional activator.
  Journal of the American Chemical Society 2009 Majmudar CY, Lee LW, Lancia JK, Nwokoye A, Wang Q, Wands AM, Wang L, Mapp AK
• Improving orthogonal tRNA-synthetase recognition for efficient unnatural amino acid incorporation and application in mammalian cells.
  Molecular bioSystems 2009 Takimoto JK, Adams KL, Xiang Z, Wang L
• Expanding the genetic code for biological studies.
  Chemistry & biology 2009 Wang Q, Parrish AR, Wang L
• Unique interactions between the chromophore and glutamate 16 lead to far-red emission in a red fluorescent protein.
  Protein science : a publication of the Protein Society 2009 Shu X, Wang L, Colip L, Kallio K, Remington SJ
• Selective labeling of proteins with chemical probes in living cells.
  Physiology (Bethesda, Md.) 2008 Lin MZ, Wang L
• Unnatural Amino Acids to Investigate Biological Processes
  Wiley Encyclopedia of Chemical Biology 2008 Johnson DBF, Takimoto JK, Xu J, Wang L
• New methods enabling efficient incorporation of unnatural amino acids in yeast.
  Journal of the American Chemical Society 2008 Wang Q, Wang L
• Manipulating proteins for neuroscience.
  Current opinion in neurobiology 2006 Parrish AR, Wang W, Wang L
• Evolving proteins in mammalian cells using somatic hypermutation.
  Nature protocols 2006 Wang L, Tsien RY
• Expanding the genetic code.
  Annual review of biophysics and biomolecular structure 2006 Wang L, Xie J, Schultz PG
• Crystal structures of apo wild-type M. jannaschii tyrosyl-tRNA synthetase (TyrRS) and an engineered TyrRS specific for O-methyl-L-tyrosine.
  Protein science : a publication of the Protein Society 2005 Zhang Y, Wang L, Schultz PG, Wilson IA
• Evolution of new nonantibody proteins via iterative somatic hypermutation.
  Proceedings of the National Academy of Sciences of the United States of America 2004 Wang L, Jackson WC, Steinbach PA, Tsien RY
• The site-specific incorporation of p-iodo-L-phenylalanine into proteins for structure determination.
  Nature biotechnology 2004 Xie J, Wang L, Wu N, Brock A, Spraggon G, Schultz PG
• Amersham Prize winner. Expanding the genetic code.
  Science (New York, N.Y.) 2003 Wang L
• A new strategy for the site-specific modification of proteins in vivo.
  Biochemistry 2003 Zhang Z, Smith BA, Wang L, Brock A, Cho C, Schultz PG
• A method for the generation of glycoprotein mimetics.
  Journal of the American Chemical Society 2003 Liu H, Wang L, Brock A, Wong CH, Schultz PG
• Generation of a bacterium with a 21 amino acid genetic code.
  Journal of the American Chemical Society 2003 Mehl RA, Anderson JC, Santoro SW, Wang L, Martin AB, King DS, Horn DM, Schultz PG
• Unnatural amino acid mutagenesis of green fluorescent protein.
  The Journal of organic chemistry 2003 Wang L, Xie J, Deniz AA, Schultz PG
• Addition of the keto functional group to the genetic code of Escherichia coli.
  Proceedings of the National Academy of Sciences of the United States of America 2002 Wang L, Zhang Z, Brock A, Schultz PG
• An efficient system for the evolution of aminoacyl-tRNA synthetase specificity.
  Nature biotechnology 2002 Santoro SW, Wang L, Herberich B, King DS, Schultz PG
• Addition of p-azido-L-phenylalanine to the genetic code of Escherichia coli.
  Journal of the American Chemical Society 2002 Chin JW, Santoro SW, Martin AB, King DS, Wang L, Schultz PG
• The selective incorporation of alkenes into proteins in Escherichia coli.
  Angewandte Chemie (International ed. in English) 2002 Zhang Z, Wang L, Brock A, Schultz PG
• Addition of a photocrosslinking amino acid to the genetic code of Escherichiacoli.
  Proceedings of the National Academy of Sciences of the United States of America 2002 Chin JW, Martin AB, King DS, Wang L, Schultz PG
• Adding L-3-(2-Naphthyl)alanine to the genetic code of E. coli.
  Journal of the American Chemical Society 2002 Wang L, Brock A, Schultz PG
• Expanding the genetic code.
  Chemical communications (Cambridge, England) 2002 Wang L, Schultz PG
• A general approach for the generation of orthogonal tRNAs.
  Chemistry & biology 2001 Wang L, Schultz PG
• A New Functional Suppressor tRNA/Aminoacyl-tRNA Synthetase Pair for the in vivo Incorporation of Unnatural Amino Acids into Proteins
  J Am Chem Soc 2000 Wang L, Magliery TJ, Liu DR, Schultz PG
• Developing High Resolution Electrical Probing System Based on Atomic Force Microscopy
  Molecular Crystals and Liquid Crystals 1997 Chen Y, Wang L, He HX, Liu ZF
• Fabrication of Gold Nanostructures on Graphite Using Atomic Force Microscope
  Molecular Crystals and Liquid Crystals 1997 Song JQ, Li CZ, He HX, Chen Y, Wang L, Liu ZF
• Force Titration of a Carboxylic Acid Terminated Self-Assemble Monolayer Using Chemical Force Microscopy
  Molecular Crystals and Liquid Crystals 1997 He HX, Li CZ, Song JQ, Mu T, Wang L, Zhang HL, Liu ZF
• NOTE
  Journal of colloid and interface science 1997 Zhu B, Zhang P, Wang L, Liu Z