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Larsen, Nicholas
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Larsen, Nicholas

Graduate Student
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Positions

  • 2012 - Senior Investigator, H3 Biomedicine
  • 2008 - 2012 Senior Scientist, AstraZeneca
  • 2003 - 2007 Leukemia and Lymphoma Society Fellow and Jane Coffin Childs Fellow, Harvard Medical School, Harvard University

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  • Doctoral Dissertation
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Publications

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  • academic article

    • Gingipalli, L., Block, M. H., Bao, L., Cooke, E., Dakin, L. A., Denz, C. R., Ferguson, A. D., Johannes, J. W., Larsen, N. A., Lyne, P. D., Pontz, T. W., Wang, T., et al. Discovery of 2,6-disubstituted pyrazine derivatives as inhibitors of CK2 and PIM kinases Bioorganic & Medicinal Chemistry Letters  2018 28:1336-1341  DOI:10.1016/j.bmcl.2018.03.018  PMID:29559278
    • Finci, L. I., Zhang, X., Huang, X., Zhou, Q., Tsai, J., Teng, T., Agrawal, A., Chan, B., Irwin, S., Karr, C., Cook, A., Zhu, P., et al. The cryo-EM structure of the SF3b spliceosome complex bound to a splicing modulator reveals a pre-mRNA substrate competitive mechanism of action Genes & Development  2018 32:309-320  DOI:10.1101/gad.311043.117  PMID:29491137  PMCID:PMC5859971
    • van Strijp, D., Vulders, R. C. M., Larsen, N. A., Schira, J., Baerlocher, L., van Driel, M. A., Podenphant, M., Hansen, T. S., Kristensen, A., Mir, K. U., Olesen, T., Verhaegh, W. F. J., et al. Complete sequence-based pathway analysis by differential on-chip DNA and RNA extraction from a single cell Scientific Reports  2017 7  DOI:10.1038/s41598-017-10704-4  PMID:28887473  PMCID:PMC5591254
    • Cowen, S. D., Russell, D., Dakin, L. A., Chen, H., Larsen, N. A., Godin, R., Throner, S., Zheng, X., Molina, A., Wu, J., Cheung, T., Howard, T., et al. Design, synthesis, and biological activity of substrate competitive SMYD2 inhibitors Journal of Medicinal Chemistry  2016 59:11079-11097  DOI:10.1021/acs.jmedchem.6b01303  PMID:28002961
    • Dowling, J. E., Alimzhanov, M., Bao, L., Chuaqui, C., Denz, C. R., Jenkins, E., Larsen, N. A., Lyne, P. D., Pontz, T., Ye, Q., Holdgate, G. A., Snow, L., et al. Potent and selective CK2 kinase inhibitors with effects on Wnt pathway signaling in vivo ACS Medicinal Chemistry Letters  2016 7:300-305  DOI:10.1021/acsmedchemlett.5b00452  PMID:26985319  PMCID:PMC4789659
    • Johannes, J. W., Almeida, L., Daly, K., Ferguson, A. D., Grosskurth, S. E., Guan, H., Howard, T., Ioannidis, S., Kazmirski, S., Lamb, M. L., Larsen, N. A., Lyne, P. D., et al. Discovery of AZ0108, an orally bioavailable phthalazinone PARP inhibitor that blocks centrosome clustering Bioorganic & Medicinal Chemistry Letters  2015 25:5743-5747  DOI:10.1016/j.bmcl.2015.10.079  PMID:26546219
    • Wu, J., Powell, F., Larsen, N. A., Lai, Z., Byth, K. F., Read, J., Gu, R. F., Roth, M., Toader, D., Saeh, J. C., Chen, H. Mechanism and in vitro pharmacology of TAK1 inhibition by (5Z)-7-Oxozeaenol ACS Chemical Biology  2013 8:643-650  DOI:10.1021/cb3005897  PMID:23272696
    • Dowling, J. E., Alimzhanov, M., Bao, L., Block, M. H., Chuaqui, C., Cooke, E. L., Denz, C. R., Hird, A., Huang, S., Larsen, N. A., Peng, B., Pontz, T. W., et al. Structure and property based design of pyrazolo 1,5-a pyrimidine inhibitors of CK2 kinase with activity in vivo ACS Medicinal Chemistry Letters  2013 4:800-805  DOI:10.1021/ml400197u  PMID:24900749  PMCID:PMC4027246
    • Larsen, N. A., Nash, T. J., Morningstar, M., Shapiro, A. B., Joubran, C., Blackett, C. J., Patten, A. D., Boriack-Sjodin, P. A., Doig, P. An aminoquinazoline inhibitor of the essential bacterial cell wall synthetic enzyme GlmU has a unique non-protein-kinase-like binding mode Biochemical Journal  2012 446:405-413  DOI:10.1042/bj20120596  PMID:22721802
    • Hennessy, E. J., Saeh, J. C., Sha, L., MacIntyre, T., Wang, H., Larsen, N. A., Aquila, B. M., Ferguson, A. D., Laing, N. M., Omer, C. A. Discovery of aminopiperidine-based Smac mimetics as IAP antagonists Bioorganic & Medicinal Chemistry Letters  2012 22:1690-1694  DOI:10.1016/j.bmcl.2011.12.109  PMID:22264476
    • Wang, T., Block, M. A., Cowen, S., Davies, A. M., Devereaux, E., Gingipalli, L., Johannes, J., Larsen, N. A., Su, Q., Tucker, J. A., Whitston, D., Wu, J., et al. Discovery of azabenzimidazole derivatives as potent, selective inhibitors of TBK1/IKKε kinases Bioorganic & Medicinal Chemistry Letters  2012 22:2063-2069  DOI:10.1016/j.bmcl.2012.01.018  PMID:22305584
    • Martinez-Botella, G., Breen, J. N., Duffy, J. E. S., Dumas, J., Geng, B. L., Gowers, I. K., Green, O. M., Guler, S., Hentemann, M. F., Hernandez-Juan, F. A., Joseph-McCarthy, D., Kawatkar, S., et al. Discovery of selective and potent inhibitors of gram-positive bacterial thymidylate kinase (TMK) Journal of Medicinal Chemistry  2012 55:10010-10021  DOI:10.1021/jm3011806  PMID:23043329
    • Dowling, J. E., Chuaqui, C., Pontz, T. W., Lyne, P. D., Larsen, N. A., Block, M. H., Chen, H., Su, N., Wu, A., Russell, D., Pollard, H., Lee, J. W., et al. Potent and selective inhibitors of CK2 kinase identified through structure-guided hybridization ACS Medicinal Chemistry Letters  2012 3:278-283  DOI:10.1021/ml200257n  PMID:24900464  PMCID:PMC4025639
    • Ferguson, A. D., Larsen, N. A., Howard, T., Pollard, H., Green, I., Grande, C., Cheung, T., Garcia-Arenas, R., Cowen, S., Wu, J., Godin, R., Chen, H., et al. Structural basis of substrate methylation and inhibition of SMYD2 Structure  2011 19:1262-1273  DOI:10.1016/j.str.2011.06.011  PMID:21782458
    • Taga, M. E., Larsen, N. A., Howard-Jones, A. R., Walsh, C. T., Walker, G. C. BluB cannibalizes flavin to form the lower ligand of vitamin B-12 Nature  2007 446:449-453  DOI:10.1038/nature05611  PMID:17377583  PMCID:PMC2770582
    • Al-Bassam, J., Larsen, N. A., Hyman, A. A., Harrison, S. C. Crystal structure of a TOG domain: Conserved features of XMAP215/Dis1-family TOG domains and implications for tubulin binding Structure  2007 15:355-362  DOI:10.1016/j.str.2007.01.012  PMID:17355870
    • Larsen, N. A., Al-Bassam, J., Wei, R. R., Harrison, S. C. Structural analysis of Bub3 interactions in the mitotic spindle checkpoint Proceedings of the National Academy of Sciences of the United States of America  2007 104:1201-1206  DOI:10.1073/pnas.0610358104  PMID:17227844  PMCID:PMC1770893
    • Larsen, N. A., Lin, H., Wei, R., Fischbach, M. A., Walsh, C. T. Structural characterization of enterobactin hydrolase IroE Biochemistry  2006 45:10184-10190  DOI:10.1021/bi060950i  PMID:16922493
    • Wei, R. R., Schnell, J. R., Larsen, N. A., Sorger, P. K., Chou, J. J., Harrison, S. C. Structure of a central component of the yeast kinetochore: The Spc24p/Spc25p globular domain Structure  2006 14:1003-1009  DOI:10.1016/j.str.2006.04.007  PMID:16765893
    • Cooper, Z. D., Narasimhan, D., Sunahara, R. K., Mierzejewski, P., Jutkiewicz, E. M., Larsen, N. A., Wilson, I. A., Landry, D. W., Woods, J. H. Rapid and robust protection against cocaine-induced lethality in rats by the bacterial cocaine esterase Molecular Pharmacology  2006 70:1885-1891  DOI:10.1124/mol.106.025999  PMID:16968810
    • Larsen, N. A., Harrison, S. C. Crystal structure of the spindle assembly checkpoint protein Bub3 Journal of Molecular Biology  2004 344:885-892  DOI:10.1016/j.jmb.2004.09.094  PMID:15544799
    • degree-related publication Larsen, N. A., de Prada, P., Deng, S. X., Mittal, A., Braskett, M., Zhu, X., Wilson, I. A., Landry, D. W. Crystallographic and biochemical analysis of cocaine-degrading antibody l5a10 Biochemistry  2004 43:8067-8076  DOI:10.1021/bi0494951  PMID:15209502
    • degree-related publication Redwan, E. R. M., Larsen, N. A., Zhou, B., Wirsching, P., Janda, K. D., Wilson, I. A. Expression and characterization of a humanized cocaine-binding antibody Biotechnology and Bioengineering  2003 82:612-618  DOI:10.1002/bit.10598  PMID:12652485
    • degree-related publication Zhu, X. Y., Larsen, N. A., Basran, A., Bruce, N. C., Wilson, I. A. Observation of an arsenic adduct in an acetyl esterase crystal structure Journal of Biological Chemistry  2003 278:2008-2014  DOI:10.1074/jbc.M210103200  PMID:12421810
    • degree-related publication Turner, J. M., Larsen, N. A., Basran, A., Barbas, C. F., Bruce, N. C., Wilson, I. A., Lerner, R. A. Biochemical characterization and structural analysis of a highly proficient cocaine esterase Biochemistry  2002 41:12297-12307  DOI:10.1021/bi026131p  PMID:12369817
    • degree-related publication Larsen, N. A., Turner, J. M., Stevens, J., Rosser, S. J., Basran, A., Lerner, R. A., Bruce, N. C., Wilson, I. A. Crystal structure of a bacterial cocaine esterase Nature Structural Biology  2002 9:17-21  DOI:10.1038/nsb742  PMID:11742345
    • degree-related publication Larsen, N. A., Heine, A., de Prada, P., Redwan, E. R., Yeates, T. O., Landry, D. W., Wilson, I. A. Structure determination of a cocaine hydrolytic antibody from a pseudomerohedrally twinned crystal Acta Crystallographica Section D-Biological Crystallography  2002 58:2055-2059  DOI:10.1107/s0907444902017420  PMID:12454464
    • degree-related publication Wentworth, P., Jones, L. H., Wentworth, A. D., Zhu, X. Y., Larsen, N. A., Wilson, I. A., Xu, X., Goddard, W. A., Janda, K. D., Eschenmoser, A., Lerner, R. A. Antibody catalysis of the oxidation of water Science  2001 293:1806-1811  DOI:10.1126/science.1062722  PMID:11546867
    • degree-related publication Larsen, N. A., Zhou, B., Heine, A., Wirsching, P., Janda, K. D., Wilson, I. A. Crystal structure of a cocaine-binding antibody Journal of Molecular Biology  2001 311:9-15  DOI:10.1006/jmbi.2001.4839  PMID:11469854
    • degree-related publication Larsen, N. A., Heine, A., Crane, L., Cravatt, B. F., Lerner, R. A., Wilson, I. A. Structural basis for a disfavored elimination reaction in catalytic antibody 1D4 Journal of Molecular Biology  2001 314:93-102  DOI:10.1006/jmbi.2001.5112  PMID:11724535
    • degree-related publication Karlstrom, A., Zhong, G. F., Rader, C., Larsen, N. A., Heine, A., Fuller, R., List, B., Tanaka, F., Wilson, I. A., Barbas, C. F., Lerner, R. A. Using antibody catalysis to study the outcome of multiple evolutionary trials of a chemical task Proceedings of the National Academy of Sciences of the United States of America  2000 97:3878-3883  DOI:10.1073/pnas.97.8.3878  PMID:10760259
    • Pellegrini, M.*, Larsen, N. A.*, Yeates, T. O., Gronbech-Jensen, N. A new constrained Langevin method: application to protein crystallographic refinement Physica A  1998 261:224-231  DOI:10.1016/s0378-4371(98)00375-6 (* = equal contribution)
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Background

education and training

  • Ph.D. in Biology, Scripps Research 1998 - 2002
  • B.A. in Chemistry and Physics, Carleton College 1994 - 1998

awards and honors

  • Special Fellow, conferred by Leukemia and Lymphoma Society, 2006
  • Fellow, conferred by Jane Coffin Childs Fund for Medical Research, 2003
  • Norton Gilula Fellowship, conferred by Scripps Research, 2001
  • National Merit Scholarship Finalist, conferred by National Merit Scholarship Corporation, 1994

advisee of

  • graduate advising relationship

    • Wilson, Ian, Ph.D.  candidacy, 1999 - 2002
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Contact

full name

  • Nicholas Andrew Larsen

geographic location

  • Scripps California 

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