Lerner, Richard A. - 上海科技大学

个人简介

Education M.D. (Medicine), Stanford University, School of Medicine, 1964 B.S., Stanford University, School of Medicine, 1959 Professional Experience 2013-2017 Institute Professor, Cell and Molecular Biology (CMB), Scripps Research 1989-2012 Cecil H. and Ida M. Green Chair in Chemistry, Scripps Research 1991-2011 President, Scripps Research 1987-1990 Director, Research Institute of Scripps Clinic 1982-1987 Chairman and Member, Department of Molecular Biology, Research Institute of Scripps Clinic 1980-1981 Member, Department of Immunopathology, Research Institute of Scripps Clinic 1980-1981 Head, Committee for the Study of Molecular Genetics, Research Institute of Scripps Clinic 1977-1979 Member, Department of Cellular and Developmental Immunology, Research Institute of Scripps Clinic 1974-1976 Member, Department of Immunopathology, Scripps Clinic and Research Foundation 1972-1973 Associate Member, Department of Experimental Pathology, Scripps Clinic and Research Foundation 1970-1971 Associate, Department of Experimental Pathology, Scripps Clinic and Research Foundation 1968-1969 Associate, Wistar Institute 1965-1967 Research Fellow, Department of Experimental Pathology, Scripps Clinic and Research Foundation

研究领域

Our laboratory is interested in catalytic antibodies, a field that takes as its principle goal an understanding of how the binding energy of proteins can be utilized to facilitate chemical transformations. This question is similar to that asked by the mechanistic enzymologist, with the important difference that the binding energy of the immune system is programmable. Accordingly, the antibody molecule with its programmable binding energy has emerged as an important tool for chemistry, not only from a practical sense but also for an understanding of reaction mechanisms and the evolution of the catalytic activity of proteins. A large variety of chemical reactions have been catalyzed by antibodies, ranging from simple acyl-transfer reactions to interesting concerted reactions, such as the Diels Alder cycloaddition. Recently, protein engineering techniques have been utilized to allow the incorporation of cofactors such as transition metals into antibodies. Recently, reactive immunization strategies have produced an aldolase antibody having impressive properties.

近期论文

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Liu T, Kuwana T, Zhang H, Vander Heiden MG, Lerner RA, Newmeyer DD. Phenotypic selection with an intrabody library reveals an anti-apoptotic function of PKM2 requiring Mitofusin-1. Plos Biology. 17: e2004413. PMID 31181072 DOI: 10.1371/journal.pbio.2004413 1 Lerner RA, Ma P, Xu H, Li J, Lu F, Ma F, Wang S, Xiong H, Wang W, Buratto D, Zonta F, Wang N, Liu K, Hua T, Yang G. Functionality independent DNA encoding of complex natural products. Angewandte Chemie (International Ed. in English). PMID 31020752 DOI: 10.1002/anie.201901485 1 Yea K, Jones TM, Jung D, Shin S, Arlian BM, Han KH, Zha Z, Kim MS, Oh YS, Zhang H, Lerner RA. An agonist antibody prefers relapsed AML for induction of cells that kill each other. Scientific Reports. 9: 3494. PMID 30837591 DOI: 10.1038/s41598-019-40087-7 1 Stepanov AV, Markov OV, Chernikov IV, Gladkikh DV, Zhang H, Jones T, Sen'kova AV, Chernolovskaya EL, Zenkova MA, Kalinin RS, Rubtsova MP, Meleshko AN, Genkin DD, Belogurov AA, Xie J, ... ... Lerner RA, et al. Autocrine-based selection of ligands for personalized CAR-T therapy of lymphoma. Science Advances. 4: eaau4580. PMID 30443597 DOI: 10.1126/sciadv.aau4580 1 Qiang M, Dong X, Zha Z, Zuo XK, Song XL, Zhao L, Yuan C, Huang C, Tao P, Hu Q, Li WG, Hu W, Li J, Nie Y, Buratto D, ... ... Lerner RA, et al. Selection of an ASIC1a-blocking combinatorial antibody that protects cells from ischemic death. Proceedings of the National Academy of Sciences of the United States of America. PMID 30042215 DOI: 10.1073/pnas.1807233115 1 Merkouris S, Barde YA, Binley KE, Allen ND, Stepanov AV, Wu NC, Grande G, Lin CW, Li M, Nan X, Chacon-Fernandez P, DiStefano PS, Lindsay RM, Lerner RA, Xie J. Fully human agonist antibodies to TrkB using autocrine cell-based selection from a combinatorial antibody library. Proceedings of the National Academy of Sciences of the United States of America. PMID 29987039 DOI: 10.1073/pnas.1806660115 1 Zheng T, Xie J, Yang Z, Tao P, Shi B, Douthit L, Wu P, Lerner RA. Antibody selection using clonal cocultivation of and eukaryotic cells in miniecosystems. Proceedings of the National Academy of Sciences of the United States of America. PMID 29915075 DOI: 10.1073/pnas.1806718115 1 Wu NC, Thompson AJ, Xie J, Lin CW, Nycholat CM, Zhu X, Lerner RA, Paulson JC, Wilson IA. A complex epistatic network limits the mutational reversibility in the influenza hemagglutinin receptor-binding site. Nature Communications. 9: 1264. PMID 29593268 DOI: 10.1038/s41467-018-03663-5 1 Yang Z, Du M, Wang W, Xin X, Ma P, Zhang H, Lerner RA. Affinity maturation of an TpoR targeting antibody in full-length IgG form for enhanced agonist activity. Protein Engineering, Design & Selection : Peds. PMID 29474709 DOI: 10.1093/protein/gzy002 1 Xu L, Carrer A, Zonta F, Qu Z, Ma P, Li S, Ceriani F, Buratto D, Crispino G, Zorzi V, Ziraldo G, Bruno F, Nardin C, Peres C, Mazzarda F, ... ... Lerner RA, et al. Design and Characterization of a Human Monoclonal Antibody that Modulates Mutant Connexin 26 Hemichannels Implicated in Deafness and Skin Disorders. Frontiers in Molecular Neuroscience. 10: 298. PMID 29018324 DOI: 10.3389/fnmol.2017.00298 1 Lang S, Xie J, Zhu X, Wu NC, Lerner RA, Wilson IA. Antibody 27F3 Broadly Targets Influenza A Group 1 and 2 Hemagglutinins through a Further Variation in VH1-69 Antibody Orientation on the HA Stem. Cell Reports. 20: 2935-2943. PMID 28930686 DOI: 10.1016/j.celrep.2017.08.084 1 Blanchard JW, Xie J, El-Mecharrafie N, Gross S, Lee S, Lerner RA, Baldwin KK. Replacing reprogramming factors with antibodies selected from combinatorial antibody libraries. Nature Biotechnology. PMID 28892074 DOI: 10.1038/nbt.3963 1 Wu NC, Xie J, Zheng T, Nycholat CM, Grande G, Paulson JC, Lerner RA, Wilson IA. Diversity of Functionally Permissive Sequences in the Receptor-Binding Site of Influenza Hemagglutinin. Cell Host & Microbe. 22: 247-248. PMID 28799910 DOI: 10.1016/j.chom.2017.07.001 1 Zha Z, Bucher F, Nejatfard A, Zheng T, Zhang H, Yea K, Lerner RA. Interferon-γ is a master checkpoint regulator of cytokine-induced differentiation. Proceedings of the National Academy of Sciences of the United States of America. PMID 28760993 DOI: 10.1073/pnas.1706915114 1 Wu NC, Xie J, Zheng T, Nycholat CM, Grande G, Paulson JC, Lerner RA, Wilson IA. Diversity of Functionally Permissive Sequences in the Receptor-Binding Site of Influenza Hemagglutinin. Cell Host & Microbe. 21: 742-753.e8. PMID 28618270 DOI: 10.1016/j.chom.2017.05.011 1 Wu NC, Grande G, Turner HL, Ward AB, Xie J, Lerner RA, Wilson IA. In vitro evolution of an influenza broadly neutralizing antibody is modulated by hemagglutinin receptor specificity. Nature Communications. 8: 15371. PMID 28504265 DOI: 10.1038/ncomms15371 1 Xie J, Sok D, Wu NC, Zheng T, Zhang W, Burton DR, Lerner RA. Immunochemical engineering of cell surfaces to generate virus resistance. Proceedings of the National Academy of Sciences of the United States of America. PMID 28396429 DOI: 10.1073/pnas.1702764114 1 Li N, Yu Z, Ji Q, Sun J, Liu X, Du M, Lerner RA, Zhang W. An enzyme-mediated protein-fragment complementation assay for substrate screening of sortase A. Biochemical and Biophysical Research Communications. PMID 28286272 DOI: 10.1016/j.bbrc.2017.03.016 1 Zhang H, Lerner RA. A Proximity-Based Assay for Identification of Ligand and Membrane Protein Interaction in Living Cells. Methods in Molecular Biology (Clifton, N.J.). 1575: 215-222. PMID 28255883 DOI: 10.1007/978-1-4939-6857-2_13 1 Lerner RA. Combinatorial antibody libraries: new advances, new immunological insights. Nature Reviews. Immunology. PMID 27374636 DOI: 10.1038/nri.2016.67 0.01 Zhang H, Du M, Xie J, Liu X, Sun J, Wang W, Xin X, Possani LD, Yea K, Lerner RA. Autocrine-Based Selection of Drugs that Target Ion Channels from Combinatorial Venom Peptide Libraries. Angewandte Chemie (International Ed. in English). PMID 27197631 DOI: 10.1002/anie.201603052 1 Zhang H, Sturchler E, Zhu J, Nieto A, Cistrone PA, Xie J, He L, Yea K, Jones T, Turn R, Di Stefano PS, Griffin PR, Dawson PE, McDonald PH, Lerner RA. Autocrine selection of a GLP-1R G-protein biased agonist with potent antidiabetic effects. Nature Communications. 6: 8918. PMID 26621478 DOI: 10.1038/ncomms9918 1 Yea K, Zhang H, Lerner RA. Activating pleiotropic receptors to kill cancer cells. Cell Cycle (Georgetown, Tex.). 0. PMID 26588245 DOI: 10.1080/15384101.2015.1118912