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The Ding Laboratory

The Ding Laboratory. The main research focus of the Ding laboratory is to develop and integrate chemical and functional genomic tools to study stem cell biology and regeneration.

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The Ding Laboratory

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  1. The Ding Laboratory

  2. The main research focus of the Ding laboratory is to develop and integrate chemical and functional genomic tools to study stem cell biology and regeneration.       Recent advances in stem cell biology may make possible new approaches for the treatment of a number of diseases including cardiovascular disease, neurodegenerative disease, musculoskeletal disease, diabetes and cancer. These approaches could involve cell replacement therapy and/or drug treatment to stimulate the body�s ownregenerative capabilities by promoting survival, migration/homing, proliferation, differentiation and reprogramming of endogenous stem/progenitor cells or more differentiated cells. However, such approaches will require identification of renewable cell sources of engraftable functional cells, an improved ability to manipulate their proliferation and differentiation, as well as a better understanding of the mechanisms that control their fate/function.

  3. Sheng Ding did his undergraduate at California Institute of Technology with Drs. Grubbs,  Rees, Goddard, Myers and Chan. His work with Dr. Grubbs (2005 Nobel Laureate in Chemistry) resulted in the "the second generation of Grubbs Catalyst", and work with Dr. Rees resulted in a 0.7 angstrom DNA structure. After he graduated from Caltech in 1999, he joined Dr. Peter Schultz lab at the Scripps Research Institute to conduct his Ph.D. studies, which opened up new avenues for developing future regenerative medicine. He then started his independent career as an Assistant Professor in the Chemistry Department at Scripps by the end of 2003. Since early 2007, Ding has been an Associate Professor at Scripps.

  4. CURRICULUM VITAE Name: Sheng Ding Position: Associate Professor Department of Chemistry The Scripps Research Institute Address: 10550 N. Torrey Pines Road TSRI, SP30-3157 La Jolla, CA 92037 Phone: (858) 784-7376; Fax: (858) 784-7882 sding@scripps.edu www.scripps.edu/chem/ding

  5. Educations: 1999 B.S. Chemistry California Institute of Technology (with Robert H. Grubbs & Douglas C. Rees) 2003 Ph.D. Chemistry The Scripps Research Institute (with Peter G. Schultz) Principle Positions Held: 2004-2007 The Scripps Research Institute Assistant Professor Chemistry Department 2007-present The Scripps Research Institute Associate Professor Chemistry Department Selected Honors and Awards: 1997 National Merit Scholar, Phi Tau Phi Honor Association. 1997 Member of Tau Beta Pai, the National Engineering Honor Society. 1997 Rosalind W. Alott Merit Award. 1998 Carnation Merit Award. 1999 Richard P. Schuster Memorial Prize. 2000 Fellowship in Biological Science, Howard Hughes Medical Institute. 2004 Award from The Michael J. Fox Foundation. 2005 Award from Juvenile Diabetes Research Foundation on RBCF Program. 2008 New Faculty Award from California Institute for Regenerative Medicine 2008 Prostate Cancer Foundation Challenge Award Keywords/Areas of Interest: Stem cells, Developmental biology, Synthetic chemistry, Functional genomics, High throughput screening, Signaling pathway

  6. Original Articles: 1. Scholl, M., Ding, S., Lee, C.W., Grubbs, R.H. Synthesis and activity of a new generation of ruthenium-based olefin metathesis catalysts coordinated with 1,3-dimesityl-4,5- dihydroimidazol-2-ylidene ligands, Org. Lett. 1, 953-956, (1999). 2. Kielkopf, C.L., Ding, S., Kuhn, P., Rees, D.C. Conformational flexibility of b-DNA at 0.74 .ang. resolution: d(CCAGTACTGG)2, J.M.B. 296, 787-801, (2000). 3. Ding, S., Gray, N.S., Ding, Q., Schultz, P.G. A concise and traceless linker strategy toward combinatorial libraries of 2,6,9-substituted purines, J. Org. Chem. 66, 8273- 8276, (2001). 4. Wu, T.Y.H., Ding, S., Gray, N.S., Schultz, P.G. Solid-phase synthesis of 2,3,5- trisubstituted indoles, Org. Lett. 3, 3827-3830, (2001). 5. Ding, S., Gray, N.S., Ding, Q., Schultz, P.G. Expanding the diversity of purine libraries, Tetrahedron Lett. 42, 8751-8755, (2001). 6. Ding, S., Gray, N.S., Ding, Q., Wu, X., Schultz, P.G. Resin-capture and release strategy toward combinatorial libraries of 2,6,9-substituted purines, J. Comb. Chem. 4, 183-186, (2002). 7. Ding, S., Gray, N.S., Wu, X., Ding, Q., Schultz, P.G. A combinatorial scaffold approach toward kinase-directed heterocycle libraries, J. Am. Chem. Soc. 124, 1594-1596, (2002). 8. Chang, Y.-T., Choi, J., Ding, S., Prieschl, E.E., Baumruker, T., Lee, J.-M., Chung, S.- K., Schultz, P.G. The synthesis and biological characterization of a ceramide library, J. Am. Chem. Soc. 124, 1856-1857, (2002). 9. Chapman, E., Ding, S., Schultz, P.G., Wong, C.-H. A potent and highly selective sulfotransferase inhibitor, J. Am. Chem. Soc. 124, 14524-14525, (2002). 10. Wu, X., Ding, S., Ding, Q., Gray, N.S., Schultz, P.G. A small molecule with osteogenesis-inducing activity in multipotent mesenchymal progenitor cells, J. Am. Chem. Soc. 124, 14520-14521, (2002).

  7. 11. Trnka, T.M., Morgan, J.P., Sanford, M.S., Wilhelm, T.E., Scholl, M., Choi, T.-L., Ding, S., Day, M.W., Grubbs, R.H. Synthesis and activity of ruthenium alkylidene complexes coordinated with phosphine and n-heterocyclic carbene ligands, J. Am. Chem. Soc. 125, 2546-2558, (2003). 12. Ding, S., Wu, T.Y.H., Brinker, A., Peters, E.C., Hur, W., Gray, N.S., Schultz, P.G. Synthetic small molecules that control stem cell fate, Proc. Natl. Acad. Sci. USA 100, 7632-7637, (2003). 13. Wu, T.Y.H., Schultz, P.G. and Ding, S. A one-pot two-step microwave assisted reaction in constructing 4,5-disubstituted pyrazolopyrimidines, Org. Lett. 5, 3587-90, (2003). 14. Wu, T.Y.H., Hassig, C., Wu, Y., Ding S. and Schultz, P.G. Design, synthesis, and activity of HDAC inhibitors with a N-formyl hydroxylamine head group, Bioorg Med Chem Lett. 14, 449-453, (2004). 15. Chen, S., Zhang, Q., Wu, X., Schultz, P.G. and Ding, S. Dedifferentiation of lineagecommitted cells by a small molecule, J. Am. Chem. Soc. 126, 410-411, (2004). 16. Zheng, L., Liu, J., Batalov, S., Zhou, D., Orth, A., Ding, S. and Schultz, P.G. An approach to genome-wide screens of expressed small interfering RNAs in mammalian cells, Proc. Natl. Acad. Sci. USA, 101, 135-140, (2004). 17. Wu, X., Ding, S., Ding, Q., Gray, N.S. and Schultz, P.G. Small molecules that induce Sheng Ding cardiomyogenesis in embryonic stem cells, J. Am. Chem. Soc 126, 1590-1591, (2004). 18. Wu, X., Walker, J., Zhang, J., Ding, S., and Schultz, P.G. Purmorphamine induces osteogenesis by activation of the hedgehog signaling pathway, Chemistry & Biology 11, 1229-1238, (2004). 19. Liu, J., Bang, A.G., Kintner, C., Orth, A.P., Chanda, S.K., Ding, S. and Schultz, P.G., Identification of the Wnt signaling activator leucine-rich repeat in Flightless interaction protein 2 by a genome-wide functional analysis, Proc. Natl. Acad. Sci. USA 102, 1927-1932, (2005). 20. Liu, J., Wu, X., Mitchell, B., Kintner, C., Ding, S. and Schultz, P.G., A smallmolecule agonist of the Wnt signaling pathway, Angewandte Chemie 117, 2023-2026, (2005).

  8. 21. Warashina, M., Min, K.H., Kuwabara, T., Huynh, A., Gage, F.H., Schultz, P.G., Ding, S. A novel synthetic small molecule that induces neuronal differentiation of adult hippocampal neural progenitor cells. Angewandte Chemie 45(4), 591-593, (2006). 22. Yao, S., Chen, S., Hao, E., Beattie, G., Hayek, A. and Ding, S. Long term selfrenewal and directed differentiations of human embryonic stem cells in chemically defined conditions, Proc. Natl. Acad. Sci. USA 103, 6907-6912, (2006). 23. Adrian, F.J., Ding, Q., Sim, T., Velentza, A., Sloan, C., Liu, Y., Zhang, G., Hur, W., Ding, S., Manley, P., Mestan, J., Fabbro, D., Gray, N.S. Allosteric inhibitors of Bcrabl- dependent cell proliferation. Nature Chemical Biology 2(2), 95-102. (2006). 24. Belvindrah, R., Nalbant, P., Ding, S., Wu, C., Bokoch, G.M., Mueller, U. Integrinlinked kinase regulates Bergmann glial differentiation during cerebellar development. Molecular and Cellular Neuroscience 33(2), 109-125. (2006). 25. Chen, S., Zhang, Q., Do, J-T., Yao, S., Yan, F., Peters, E.C., Schöler, H.R., Schultz, P.G. and Ding, S. A small molecule that sustains self-renewal of embryonic stem cells. Proc. Natl. Acad. Sci. USA 103, 17266-17271, 2006. 26. Zhao, Y. and Ding, S. A high-throughput siRNA library screen identifies negative regulators of osteogenesis in human mesenchymal stem cells. Proc. Natl. Acad. Sci. USA, 104: 9673-9678, 2007. 27. Chen, S.; Takanashi, S.; Zhang, Q.; Xiong, W.; Peters, E.C.; Ding, S. & Schultz, P.G. Reversine induces cellular reprogramming of lineage-committed mammalian cells. Proc. Natl. Acad. Sci. USA, 104: 10482-10487, 2007. 28. Zhang, Q., Major, B., Takanashi, S., Camp, N.D., Nishiya, N., Ginsberg, M., Schultz, P.G., Moon, R.T. & Ding, S. A small molecule synergist of the Wnt signaling pathway. Proc. Natl. Acad. Sci. USA, 104: 7444, 2007. 29. Qyang, Y., Martin-Puig, S., Chiravuri, M., Chen, S., Granger, A., Bu, L., Jiang, X., Moretti, A., Caron, L., Clarke, J., Laugwitz, K.-L., Moon, R.T., Gruber, P., Ding, S. & Chien, K.R. A cardiac mesenchymal niche differentially controls the prespecification and renewal of Isl1+ cardiovascular progenitors via a paracrine canonical Wnt pathway. Cell Stem Cell 1, 165-179, (2007). 30. Shi, Y., Do, J-T, Desponts, C., Hahm, H-S, Schöler, H.R. & Ding, S. A combined chemical and genetic approach for the generation of induced pluripotent stem cells. Cell Stem Cell 2, 525-528, (2008).

  9. 31. Shi, Y., Desponts, C., Do, J-T, Hahm, H-S, Schöler, H.R. & Ding, S. Induction of pluripotent stem cells from mouse embryonic fibroblasts by oct4 and klf4 with smallmolecule compounds. Cell Stem Cell 3, 568-574, (2008). Sheng Ding 32. Li, W., Wei, W., Zhu, S., Zhu, J., Shi, Y., Lin, T., Hao, E., Hayek, A., Deng, H. and Ding, S. Generation of Rat and Human Induced Pluripotent Stem Cells by Combining Genetic Reprogramming and Chemical Inhibitors. Cell Stem Cell 4, 16-19 (2009). 33. Wu, D. et al. A conserved mechanism for control of human and mouse embryonic stem cell pluripotency and differentiation by Shp2 tyrosine phosphatase. PLoS One 4(3), (2009). 34. Yang, W. et al. Pluripotin combined with leukemia inhibitory factor greatly promotes the derivation of embryonic stem cell lines from refractory strains. Stem Cells 27(2), 383-389, (2009). 35. Zhou, H. et al. Generation of Induced Pluripotent Stem Cells Using Recombinant Proteins. Cell Stem Cell, 4, 381-384, (2009).

  10. Invited Reviews & Book Chapters: 1. Ding, S. and Schultz, P.G. A role for chemistry in stem cell biology, Nature Biotechnology 22, 833-840, (2004). 2. Zheng, L. and Ding, S. Mammalian genome-wide loss-of-function screens using arrayed small interfering RNA expression libraries, Discovery Medicine 4, 102-105 (2004). 3. Ding, S. and Schultz, P.G., Small molecules and future regenerative medicine, Current Topics in Medicinal Chemistry 5, 383-396 (2005). 4. Chen, S., Hilcove, S. and Ding, S. Exploring stem cell biology with small molecules. Molecular Biosystems 2(1), 18, (2006). 5. Zhao, Y., Clark, J. Ding, S. Genomic studies in stem cell systems. Current Opinion in Molecular Therapeutics 7(6), 543-550, (2005). 6. Clark J, Ding S. Generation of RNAi Libraries for High-Throughput Screens. J Biomed Biotechnol. 4, 45716, (2006). 7. Wu, T.Y.H. and Ding, S. Applying chemical tools to the discovery of novel regenerative medicine, Drug Discovery Today: Technologies, 3, 255-260, (2006). 8. Wu, T.Y.H. and Ding, S. “Target validation in chemogenomics”. Target Validation in Drug Discovery, Academic Press/Elsevier, Inc. San Diego, CA (2006). 9. Chen, S. and Ding, S. “GSK3 and stem cells”. GSK and its inhibitors, John Wiley & Sons, Inc. Hoboken, NJ (2006). 10. Wen, X. and Ding, S. “Chemical and functional genomic approaches to study stem cell biology and regeneration”, Principles of Developmental Genetics, Academic Press/Elsevier, Inc. San Diego, CA (2006). 11. Clark, JH and Ding, S. “Controlling self-renewal and differentiation of hES cells in chemically defined conditions”. Human embryonic stem cells: a practical handbook, John Wiley & Sons, Inc. Hoboken, NJ (2007). 12. Xu, Y. and Ding, S. “Small Molecules in Stem Cell Research”, Wiley Encyclopedia of Chemical Biology, John Wiley & Sons, Inc. Hoboken, NJ (2007). 13. Editor and contributor, Functional Genomics in Stem Cells. John Wiley & Sons, Inc. Hoboken, NJ (2007). 14. Emre, N., Coleman, R. & Ding, S. Current Opinion in Chemical Biology 11:252–258 (2007). 15. Ambasudhan, R., Ding, S. An "Orphan" Finds a Home in NSC Regulation. Chemistry & Sheng Ding Biology 14(9), 974-975, (2007). 16. Xu, Y., Shi, Y. & Ding, S. A chemical approach to stem cell biology and regenerative medicine. Nature 453, 338-44 (2008). 17. Editor and contributor, “Dedifferentiation and Reprogramming” series in Methods in Molecular Biology, (2009). 18. Abujarour, R. & Ding, S. Induced pluripotent stem cells free of exogenous reprogramming factors. Genome Biology 10:220, (2009).

  11. Patents: 1. Ding, S., Ding, Q., Gray, N.S., Schultz, P.G. Methods for the synthesis of substituted purines. PCT Int. Appl. (2003), WO 2003031405 A2 20030417. 2. Ding, S.; Ding, Q.; Gray, N.S. C2-, C6- and 9-Aryl-substituted purine and other heteroaryl kinase inhibitor scaffolds and methods for their preparation. PCT Int. Appl. (2003), WO 2003031406 A2 20030417. 3. Liao, J., Ding, S., Schultz, P.G. cDNAs encoding human sweet taste receptors and methods for drug screening. PCT Int. Appl. (2003), WO 2003025137 A2 20030327. 4. Ding, S., Wu, T., Gray, N., Schultz, P.G. Kinase-modulating heterocyclic compounds that induce neuronal differentiation in embryonic stem cells, and useful in the treatment of kinase signalling-associated diseases. PCT Int. Appl. (2004), WO 2004093812 A2 20041104. 5. Wu, X., Ding, S., Gray, N.S. Purine derivatives for inducing osteogenesis. U.S. Pat. Appl. Publ. (2004), US 2004157864 A1 20040812. 6. Wu, X., Ding, S., Schultz, P.G. 2,4-Diaminopyrimidines as inducers of cardiomyogenesis, their preparation and use in the treatment of cardiomyopathy. PCT Int. Appl. (2005), WO 2005068437 A1 20050728. 7. Chen, S., Ding, S., Schultz, P.G. Compositions and methods for inducing cell dedifferentiation. PCT Int. Appl. (2005), WO 2005047524 A2 20050526. 8. Zheng, L.; Ding, S.; Schultz, P.G. PCR-derived siRNA expression cassettes comprising dual polIII promoters. PCT Int. Appl. (2005), WO 2005021733 A2 20050310. 9. Ding, S.; Liu, J., Schultz, P.G. Pyrimidine compounds and compositions as Wnt signaling pathway modulators. PCT Int. Appl. (2006), WO 2006078886 A2 20060727. 10. Wu, Xu; Ding, Sheng; Schultz, Peter G. Compounds and compositions as hedgehog pathway modulators. PCT Int. Appl. (2006), WO 2006050351 A2 20060511. 11. Liao, J., Ding, S., Rosen, H., Schultz, P.G. Methods and compositions using G proteincoupled receptor GPR43 or GPR41 modulators for treating insulin resistance and obesity-induced diseases, and screening methods. PCT Int. Appl. (2006), WO 2006102653 A2 20060928. 12. Chen, S.; Ding, S.; Yan, F.; Schultz, P.G. Preparation of pyrimidopyrimidinones that maintain pluripotency of embryonic stem cells. PCT Int. Appl. (2006), WO 2006135824 A1 20061221. 13. Zhang, Q.; Ding, S.; Schultz, P.G. Methods and compositions for modulating WNT signaling pathway. PCT Int. Appl. (2006), WO 2006116503 A2 20061102. 14. Micklash, K.J.; Hong, J.; Mainquist, J. K.; Ding, S.; Downs, R. C.; Schultz, P.G. Automated cellular assaying systems, high throughput and automated cellular Patents: 1. Ding, S., Ding, Q., Gray, N.S., Schultz, P.G. Methods for the synthesis of substituted purines. PCT Int. Appl. (2003), WO 2003031405 A2 20030417. 2. Ding, S.; Ding, Q.; Gray, N.S. C2-, C6- and 9-Aryl-substituted purine and other heteroaryl kinase inhibitor scaffolds and methods for their preparation. PCT Int. Appl. (2003), WO 2003031406 A2 20030417. 3. Liao, J., Ding, S., Schultz, P.G. cDNAs encoding human sweet taste receptors and methods for drug screening. PCT Int. Appl. (2003), WO 2003025137 A2 20030327. 4. Ding, S., Wu, T., Gray, N., Schultz, P.G. Kinase-modulating heterocyclic compounds that induce neuronal differentiation in embryonic stem cells, and useful in the treatment of kinase signalling-associated diseases. PCT Int. Appl. (2004), WO 2004093812 A2 20041104. 5. Wu, X., Ding, S., Gray, N.S. Purine derivatives for inducing osteogenesis. U.S. Pat. Appl. Publ. (2004), US 2004157864 A1 20040812. 6. Wu, X., Ding, S., Schultz, P.G. 2,4-Diaminopyrimidines as inducers of cardiomyogenesis, their preparation and use in the treatment of cardiomyopathy. PCT Int. Appl. (2005), WO 2005068437 A1 20050728. 7. Chen, S., Ding, S., Schultz, P.G. Compositions and methods for inducing cell dedifferentiation. PCT Int. Appl. (2005), WO 2005047524 A2 20050526. 8. Zheng, L.; Ding, S.; Schultz, P.G. PCR-derived siRNA expression cassettes comprising dual polIII promoters. PCT Int. Appl. (2005), WO 2005021733 A2 20050310. 9. Ding, S.; Liu, J., Schultz, P.G. Pyrimidine compounds and compositions as Wnt signaling pathway modulators. PCT Int. Appl. (2006), WO 2006078886 A2 20060727. 10. Wu, Xu; Ding, Sheng; Schultz, Peter G. Compounds and compositions as hedgehog pathway modulators. PCT Int. Appl. (2006), WO 2006050351 A2 20060511. 11. Liao, J., Ding, S., Rosen, H., Schultz, P.G. Methods and compositions using G proteincoupled receptor GPR43 or GPR41 modulators for treating insulin resistance and obesity-induced diseases, and screening methods. PCT Int. Appl. (2006), WO 2006102653 A2 20060928. 12. Chen, S.; Ding, S.; Yan, F.; Schultz, P.G. Preparation of pyrimidopyrimidinones that maintain pluripotency of embryonic stem cells. PCT Int. Appl. (2006), WO 2006135824 A1 20061221. 13. Zhang, Q.; Ding, S.; Schultz, P.G. Methods and compositions for modulating WNT signaling pathway. PCT Int. Appl. (2006), WO 2006116503 A2 20061102. 14. Micklash, K.J.; Hong, J.; Mainquist, J. K.; Ding, S.; Downs, R. C.; Schultz, P.G. Automated cellular assaying systems, high throughput and automated cellular

  12. disruption systems for cellular motility assays and other assay types. U.S. Pat. Appl. Publ. (2007), US 2007105214 A1 20070510. 15. Warashina, M.; Min, K.H.; Gage, F.; Schultz, P.G.; Ding, S. Compositions comprising aminothiazole compounds and methods for inducing neuronal differentiation for treating neurodegenerative diseases. PCT Int. Appl. (2007), WO 2007064891 A1 20070607. 16. Zhao, Y.X. & Ding, S. Pharmaceutical compositions containing siRNAs for the treatment of osteogenesis by inhibition of osteogenic suppressors. PCT Int. Appl. (2008), WO 2008019159 A2 20080214. Professional Organizations: Member of American Chemical Society, 1997-present Member of American Society for Cell Biology, 2003-present Member of International Society for Stem Cell Research, 2003-present Grant/Award Review Committee 1. NIH Study Section, Assay Development for High Throughput Molecular Screening, 2005. 2. Rapid Wound Healing Technology Development Project, US Army, 2006. 3. European Young Investigator Award, 2007. 4. Maryland Stem Cell Review Committee, 2007. 5. New Jersey Stem Cell Research Grant Program, 2007. 6. American Heart Association, 2008. 7. New York State Stem Cell Review, 2008. 8. SIMM, CAS, 2008. 9. Juvenile Diabetes Research Foundation grant review, 2009.

  13. Other Activities: 2004-present: Thesis committee member for TSRI graduate students. 2006- 2008 : San Diego Stem Cell Course Steering Committee. 2003-2007 : Consultant for Genomics Institute of the Novartis Research Foundation. 2007-present : Co-founder, SAB of Fate Therapeutics, Inc. 2008-present : Co-founder, SAB of Stemgent, Inc. 2008 : Executive review committee for Institute for Integrated Cell-Material Sciences (iCeMS)/WPI program at Kyoto University, Japan. 2008-present : Director of CIRM-Scripps Stem Cell HTS Center

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