Curriculum Vitae Name: Address: Telephone: Email: Daiguan Yu 190 Kai Yuan Avenue, Science Park, Guangzhou, China 86-20-32015322 daiguanyu98@hotmail.com ________________________________________________________________________ WORK EXPERIENCE 2011—Present, Head of Biotherapeutics Lab., Drug Discovery Pipeline (DDP), Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences (CAS), Guangzhou, China Therapeutic protein development. Developing ADAMTS13 as therapeutic protein for treatment of thrombotic thrombocytopenic purpura (TTP). In charge of a core for gene knockout and transgenic construction (DNA vectors and ES cell clone development) 2009—2010, Wellcome Trust Sanger Institute, Hinxton, Cambridge, UK, Scientific Specialist in the project for developing antibody humanized mice. In charge of IgL project including landing pad targeting vector design and construction, human IgL BAC selection, BAC modification etc. IgK landing pad vector design and construction IgH flip-over vector (for inactivating the mouse endogenous IgH ) design and construction. Developing the strategy for two BAC combinations in E.coli using recombineering. Construction of ES cell line for IgL landing pad vector Contributed to the RMCE strategy for human BAC insertion December 2000—February 2009, Scientist, Senior Scientist and Project Leader, Lexicon Pharmaceuticals Inc., The Woodlands, Texas, USA Worked closely with therapeutic area counterparts in Metabolism, Cardiology, Immunology, and Ophthalmology to create design goals of recombinant adenoviruses and then proceeded to deliver and use the customized adenoviruses for target validation, creation of disease models and recombinant protein production Led a group to design, construct, purify and produce hundreds of recombinant adenovirus and use these recombinant adenovirus to screen and validate drug targets by over-expression of gene targets in vivo (in mice), including therapeutic protein and antibody targets. 1 Developed a one-step method for construction of recombinant adenovirus vectors Managed a therapeutic protein project, as project leader, responsible for the protein construct design, cell line generation, protein purification and production, functional assay development and coordination of in vivo tests Participated in antibody engineering, including antibody (V and C regions) cloning, expression in CHO cells, chimera antibody construction, antibody affinity assay Developed a protein production platform using recombinant adenovirus for tens of milligrams of recombinant protein Involved in murine disease model development using recombinant adenovirus to create the pathological condition Performed cell based assays using recombinant adenovirus Constructed gene knockout DNA vectors November 1999-- December 2000, Research Fellow, National Cancer InstituteFrederick, Maryland, USA, Modified bacterial artificial chromosomes (BAC) using bacteriophage homologous recombination system (recombineering) Further optimized and implemented in vivo DNA engineering using bacteriophage homologous recombination system (recombineering) Screened and selected genes in E. coli that affect DNA engineering with bacteriophage homologous recombination system (recombineering) February 1995--October 1999, Postdoctoral Research Fellow, ABL-Basic Research Program at the National Cancer Institute-Frederick Cancer Research and Development Center, Frederick, Maryland, USA Developed “Recombineering” technology using bacteriophage homologous recombination system Modified bacterial artificial chromosomes (BAC) using bacteriophage homologous recombination system (recombineering) Purified the protein RNaseIII for its crystallization Worked on the Regulation of the phage N gene expression at transcriptional and translational levels Screened and selected the E. coli host mutants defective for N autoregulation August 1994--January 1995, Research Associate, Department of Agricultural Chemistry, The University of Sydney, Australia Selected ammonia-resistant mutants in Azospirillum March 1990--February 1991, Visiting Scholar, Department of Agricultural Chemistry, The University of Sydney, Australia Worked on the effect of 2,4-D on enzymatic activity of glutamine synthetase (GS) and glutamate dehydrogenase (GDH) in wheat roots 2 August 1988--February 1990, Senior Research Associate, Institute of Soils and Fertilizers, Chinese Academy of Agricultural Sciences, Beijing, China Worked on nitrogen fixation in chemically induced system of Rhizobium/nonlegume crops February 1982--July 1985, Research Associate, Institute of Soils and Fertilizers, Chinese Academy of Agricultural Sciences, Beijing, China Worked on isolation, identification and application of Rhizobium strains in forage legumes EDUCATION Ph. D., University of Sydney, Australia (1995) M. Sc., Microbiology, The Graduate School of Chinese Academy of Agricultural Sciences, Beijing, China (1988) B. Sc., Microbiology and Biochemistry, Lanzhou University, Lanzhou, China (1982) HONORS/AWARDS 2010 Federal Laboratory Consortium National Award (with a group) for “Excellence in Technology Transfer”, USA 2009 Federal Laboratory Consortium Mid-Atlantic Region Award (with a group) for “Innovative Techniques and Reagents for Improved Genetic Engineering”, USA Technology Transfer Award (myself), 2000, National Cancer Institute, National Institutes of Health, USA Invention License for “In vivo and in vitro DNA engineering using the recombination system (red) of bacteriophage lambda” (myself),1999, National Cancer Institute, National Institutes of Health, USA Special Overseas Postgraduate Award, February 1991--February 1994, Australian federal government (Department of Employment, Education and Training), Australia International Postgraduate Research Award, February 1991--February 1994, The University of Sydney, Australia Scientific and Technological Improvement Award (with a group) for “Isolation, identification and application of Rhizobium strains in forage legumes”, 1985, Ministry of Agriculture of China, Beijing, China 3 PUBLICATIONS AND PATENTS William K. Sonnenburg *, Daiguan Yu*, E-Chiang Lee, Wei Xiong, Billie Key, Urvi Desai, Zhi-Ming Ding, David R. Powell, and Greg Landes (2009). Glycosylphosphatidylinositol-anchored high-density lipoprotein-binding protein (GPIHBP1) stabilizes lipoprotein lipase (LPL) and prevents its inactivation by angiopoietin-like 3 (ANGPTL3) and angiopoietin-like 4 (ANGPTL4). J. Lipid Res. Dec. 50(12):2421-9 (*William K. Sonnenburg and Daiguan Yu contributed equally to this work.) Helen R. Wilson*, Jian-guang Zhou*, Daiguan Yu* and Donald L. Court (2004). Translation repression by an RNA polymerase elongation complex. Mol Microbiol. Aug;53(3):821-8. (* Helen R. Wilson, Jian-guang Zhou and Daiguan Yu contributed equally to this work.) Daiguan Yu, James A. Sawitzke and Donald L. Court (2003). Recombineering with overlapping single-stranded DNA oligonucleotides: testing a recombination intermediate. Proc Natl Acad Sci U S A. Jun 10;100(12):7207-12 Donald L. Court, Srividya Swaminathan, Daiguan Yu, Helen R. Wilson, Teresa Baker, Michael Bubunenko, James A. Sawitzke and Shyam K. Sharan (2003) Minilambda: a tractable system for chromosome and BAC engineering. Gene. 2003, Oct 2;315:63-9 Helen R. Wilson, Daiguan Yu, Howard K. Peters, III, Jian-guang Zhou and Donald L. Court (2002). The global regulator RNase III modulates translation repression by the transcription elongation factor N. EMBO J, 21(15):4154-61 Srividya Swaminathan , Hilary M. Ellis , Laura S. Waters , Daiguan Yu , E-Chiang Lee , Donald L. Court , Shyam K. Sharan (2001). Rapid engineering of bacterial artificial chromosomes using oligonucleotides. Genesis, 29(1):14-21 Hilary M. Ellis, Daiguan Yu, Tina DiTizio and Donald L. Court (2001). High efficiency mutagenesis, repair, and engineering of chromosomal DNA using single-stranded oligonucleotides. Proc. Natl. Acad. Sci. USA, 98(12):6742-6 E-Chiang Lee, Daiguan Yu, J. Martinez de Velasco, Deborah A. Swing, Lino Tessarollo, Donald L. Court, Nancy A. Jenkins and Neal G. Copeland (2001). A high efficient E. coli-based chromosome engineering system adapted for functional genomics studies in mouse. Genomics,73(1):56-65. Kirill Sergueev, Daiguan Yu, Stuart Austin and Donald Court (2001). Cell toxicity caused by products of the pL operon of bacteriophage lambda. Gene, 272(12):227-35 4 Daiguan Yu, Hilary M. Ellis, E-Chiang Lee, Nancy A. Jenkins, Neal G. Copeland and Donald L. Court (2000). An efficient recombination system for chromosome engineering in E. coli. Proc. Natl. Acad. Sci. USA 97(11); 5978-5983. Daiguan Yu and Donald Court (1998). A new system to place single copies of genes, sites and lacZ fusions on the E. coli chromosome. Gene, 223(1-2);77-81 Daiguan Yu and Ivan R. Kennedy (1995). Nitrogenase activity (C2H2 reduction) of Azorhizobium in 2,4-D induced root structures of wheat. Soil Biology and Biochem. 27;459-462 Daiguan Yu and Ivan R. Kennedy (1993). Measurement of the rate of biological nitrogen fixation. In: Biological Nitrogen Fixation: A Manual for the Study of Associative System (ed. I.R. Kennedy) pp. 1-18. Sridevy Sriskandarajah, Ivan R. Kennedy, Daiguan Yu and Yao Tseng Tchan (1993). Effect of plant growth regulators on acetylene-reducing associations between Azospirillun brasilense and wheat. Plant and Soil 153;165-178. Daiguan Yu, Ivan R. Kennedy and Yao Tseng Tchan (1993). Verification of nitrogenase activity (C2H2 reduction) in Azospirillum populated, 2,4-D induced, root structures of wheat. Aust. J. Plant Physiol. ,20;187-195. Daiguan Yu (1990). Does bacterioid have the cell wall? Microbiology (Chinese),3;46-49. Daiguan Yu and Ting-Wei Chen (1989). Studies on the 2,4-D induction of wheat nodules and the introduction of Rhizobium into the nodule cells. Proceedings of the Symposium of Beijing International Conference on Biotechnology, July 1989 Beijing, China. Ting-Wei Chen, Ying-Xian Xie, Wan-Hua Chen, Daiguan Yu and Jing Xu (1988). Studies on a new system of biological nitrogen fixation for non-legume crops. Nature Journal (Chinese), 11;163-167. Daiguan Yu, Guo-Zan Ning and Yuan-Fang Li (1988). Rhizobium sp. astrugalas: Analysis of serological types and competition on nodulation. Soil and Fertilizer (Chinese), 4;45-47. Guo-Zan Ning, Yuan-Fang Li, Yuying Wu, Yanling Huang and Daiguan Yu (1987). Production and application of Rhizobium inoculants for forage legumes in China. Grassland of China (Chinese), 1;60-63. Yuan-Fang Li, Guo-Zan Ning, Yuying Wu, Yanling Huang and Daiguan Yu (1987). Leucaena: A useful legume woody plant. World Agriculture (Chinese), 2;26-28. 5 Guo-Zan Ning, Yuan-Fang Li, Yuying Wu, Yanling Huang and Daiguan Yu (1986). Studies on the aerial seedling of rhizobia inoculation Astrugalasadsurgens Pall. Agri. Sc. China (Chinese), 5;85-91. Guo-Zan Ning, Yuan-Fang Li, Yuying Wu, Yanling Huang and Daiguan Yu (1986). Physiological properties and application of Rhizobium sp.astrugalas CA8116. J. Microbiology (Chinese), 2;50-52. Yuan-Fang Li, Guo-Zan Ning, Yuying Wu, Yanling Huang and Daiguan Yu (1986). Selection and physiological research of acid resistant strain of Rhizobium sp. leucaena. J. Microbiology (Chinese), 2;5-9. Guo-Zan Ning, Yuan-Fang Li, Yuying Wu, Yanling Huang and Daiguan Yu (1985). Effect of inoculating Rhizobium trifolii on clover. Grassland of China (Chinese), 3;60-63. Daiguan Yu and Yuan-Fang Li (1984). Application of seed coating in agriculture. Science and Technology of International Agriculture (Chinese), 11;35-37. Guo-Zan Ning, Yuan-Fang Li, Yuying Wu, Yanling Huang and Daiguan Yu (1984). Selection and application of Rhizobium sp. astrugalas. Soil and Fertilizer (Chinese), 6;35-38. Patent # 71447345: Enhanced Homologous Recombination Mediated By Lambda Recombination Proteins (issued December 5, 2006, National Cancer Institute, National Institutes of Health, USA) 6