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Kishi, Shuji
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Kishi, Shuji

Faculty Member
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Positions

  • 2009 - Adjunct Professor, Center for Biology & Biotechnology, Florida Atlantic University
  • 2017 Associate Professor, Molecular Medicine , Scripps Research
  • 2015 - 2017 Associate Professor, Metabolism and Aging , Scripps Research
  • 2009 - 2017 Faculty Member, Skaggs Graduate School of Chemical and Biological Sciences , Scripps Research
  • 2009 - 2015 Assistant Professor, Metabolism and Aging , Scripps Research
Dr. Shuji Kishi aims to develop a high-throughput processing system for gene identification and phenotype characterization particularly associated with age-related disorders in humans, using zebrafish as an amenable vertebrate model system.

Research Areas research areas

  • Aging (UMLS)
  • Arthritis (UMLS)
  • Blindness (UMLS)
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Publications

recent publications

  • academic article

    • Song, Y., Zhou, H., Vo, M. N., Shi, Y., Nawaz, M. H., Vargas-Rodriguez, O., Diedrich, J. K., Yates III, J. R., Kishi, S., Musier-Forsyth, K., Schimmel, P. Double mimicry evades tRNA synthetase editing by toxic vegetable-sourced non-proteinogenic amino acid Nature Communications  2017 8  DOI:10.1038/s41467-017-02201-z  PMID:29273753  PMCID:PMC5741666
    • Sasaki, T., Lian, S., Khan, A., Llop, J. R., Samuelson, A. V., Chen, W. B., Klionsky, D. J., Kishi, S. Autolysosome biogenesis and developmental senescence are regulated by both Spns1 and v-ATPase Autophagy  2017 13:386-403  DOI:10.1080/15548627.2016.1256934  PMID:27875093  PMCID:PMC5324850
    • Song, Y., Shi, Y., Carland, T. M., Lian, S., Sasaki, T., Schork, N. J., Head, S. R., Kishi, S., Schimmel, P. p53-Dependent DNA damage response sensitive to editing-defective tRNA synthetase in zebrafish Proceedings of the National Academy of Sciences of the United States of America  2016 113:8460-8465  DOI:10.1073/pnas.1608139113  PMID:27402763  PMCID:PMC4968768
    • Kishi, S., Bayliss, P. E., Hanai, J. I. A prospective epigenetic paradigm between cellular senescence and epithelial-mesenchymal transition in organismal development and aging Translational Research  2015 165:241-249  DOI:10.1016/j.trsl.2014.05.007  PMID:24924348
    • Wei, N., Shi, Y., Truong, L. N., Fisch, K. M., Xu, T., Gardiner, E., Fu, G., Hsu, Y. S. O., Kishi, S., Su, A. I., Wu, X., Yang, X. L. Oxidative stress diverts tRNA synthetase to nucleus for protection against DNA damage Molecular Cell  2014 56:323-332  DOI:10.1016/j.molcel.2014.09.006  PMID:25284223  PMCID:PMC4224670
    • Shi, Y., Xu, X., Zhang, Q., Fu, G., Mo, Z., Wang, G. S., Kishi, S., Yang, X. L. tRNA synthetase counteracts c-Myc to develop functional vasculature Elife  2014 3:e02349  DOI:10.7554/eLife.02349  PMID:24940000  PMCID:PMC4057782
    • Kishi, S. Using zebrafish models to explore genetic and epigenetic impacts on evolutionary developmental origins of aging Translational Research  2014 163:123-135  DOI:10.1016/j.trsl.2013.10.004  PMID:24239812  PMCID:PMC3969878
    • Sasaki, T., Lian, S., Qi, J., Bayliss, P. E., Carr, C. E., Johnson, J. L., Guha, S., Kobler, P., Catz, S. D., Gill, M., Jia, K., Klionsky, D. J., et al. Aberrant autolysosomal regulation is linked to the induction of embryonic senescence: differential roles of Beclin 1 and p53 in vertebrate Spns1 deficiency PLoS Genetics  2014 10:e1004409  DOI:10.1371/journal.pgen.1004409  PMID:24967584  PMCID:PMC4072523
    • Sasaki, T., Kishi, S. Molecular and chemical genetic approaches to developmental origins of aging and disease in zebrafish Biochimica et Biophysica Acta  2013 1832:1362-1370  DOI:10.1016/j.bbadis.2013.04.030  PMID:23660559  PMCID:PMC3746063
    • Sajish, M., Zhou, Q. S., Kishi, S., Valdez, D. M., Kapoor, M., Guo, M., Lee, S., Kim, S., Yang, X. L., Schimmel, P. Trp-tRNA synthetase bridges DNA-PKcs to PARP-1 to link IFN-γ and p53 signaling Nature Chemical Biology  2012 8:547-554  DOI:10.1038/nchembio.937  PMID:22504299  PMCID:PMC3780985
    • Xu, X. L., Shi, Y., Zhang, H. M., Swindell, E. C., Marshall, A. G., Guo, M., Kishi, S., Yang, X. L. Unique domain appended to vertebrate tRNA synthetase is essential for vascular development Nature Communications  2012 3:681  DOI:10.1038/ncomms1686  PMID:22353712  PMCID:PMC3293412
    • Kishi, S. The search for evolutionary developmental origins of aging in zebrafish: a novel intersection of developmental and senescence biology in the zebrafish model system Birth Defects Research Part C-Embryo Today-Reviews  2011 93:229-248  DOI:10.1002/bdrc.20217  PMID:21932432
    • Koshimizu, E., Imamura, S., Qi, J., Toure, J., Valdez, D. M., Carr, C. E., Hanai, J., Kishi, S. Embryonic senescence and laminopathies in a progeroid zebrafish model PLoS One  2011 6:e17688  DOI:10.1371/journal.pone.0017688  PMID:21479207  PMCID:PMC3068137
    • Kishi, S., Slack, B. E., Uchiyama, J., Zhdanova, I. V. Zebrafish as a genetic model in biological and behavioral gerontology: where development meets aging in vertebrates. A mini-review Gerontology  2009 55:430-441  DOI:10.1159/000228892  PMID:19654474  PMCID:PMC2820570
    • Imamura, S., Uchiyama, J., Koshimizu, E., Hanai, J. I., Raftopoulou, C., Murphey, R. D., Bayliss, P. E., Imai, Y., Burns, C. E., Masutomi, K., Gagos, S., Zon, L. I., et al. A non-canonical function of zebrafish telomerase reverse transcriptase is required for developmental hematopoiesis PLoS One  2008 3:e3364  DOI:10.1371/journal.pone.0003364  PMID:18846223  PMCID:PMC2561060
    • Kishi, S., Bayliss, P. E., Uchiyama, J., Koshimizu, E., Qi, J., Nanjappa, P., Imamura, S., Islam, A., Neuberg, D., Amsterdam, A., Roberts, T. M. The identification of zebrafish mutants showing alterations in senescence-associated biomarkers PLoS Genetics  2008 4:e1000152  DOI:10.1371/journal.pgen.1000152  PMID:18704191  PMCID:PMC2515337
    • Sidi, S., Sanda, T., Kennedy, R. D., Hagen, A. T., Jette, C. A., Hoffmans, R., Pascual, J., Imamura, S., Kishi, S., Amatruda, J. F., Kanki, J. P., Green, D. R., et al. Chk1 suppresses a caspase-2 apoptotic response to DNA damage that bypasses p53, Bcl-2, and caspase-3 Cell  2008 133:864-877  DOI:10.1016/j.cell.2008.03.037  PMID:18510930  PMCID:PMC2719897
    • Zhdanova, I. V., Yu, L., Lopez-Patino, M., Shang, E., Kishi, S., Gueling, E. Aging of the circadian system in zebrafish and the effects of melatonin on sleep and cognitive performance Brain Research Bulletin  2008 75:433-441  DOI:10.1016/j.brainresbull.2007.10.053  PMID:18331912  PMCID:PMC2323434
    • Hanai, J. I., Cao, P., Tanksale, P., Imamura, S., Koshimizu, E., Zhao, J. H., Kishi, S., Yamashita, M., Phillips, P. S., Sukhatme, V. P., Lecker, S. H. The muscle-specific ubiquitin ligase atrogin-1/MAFbx mediates statin-induced muscle toxicity Journal of Clinical Investigation  2007 117:3940-3951  DOI:10.1172/jci32741  PMID:17992259  PMCID:PMC2066198
    • Tsai, S. B., Tucci, V., Uchiyama, J., Fabian, N. J., Lin, M. C., Bayliss, P. E., Neuberg, D. S., Zhdanova, I. V., Kishi, S. Differential effects of genotoxic stress on both concurrent body growth and gradual senescence in the adult zebrafish Aging Cell  2007 6:209-224  DOI:10.1111/j.1474-9726.2007.00278.x  PMID:17376146
    • Yu, L. L., Tucci, V., Kishi, S., Zhdanova, I. V. Cognitive aging in zebrafish PLoS One  2006 1:e14  DOI:10.1371/journal.pone.0000014  PMID:17183640  PMCID:PMC1762370
    • Imamura, S., Kishi, S. Molecular cloning and functional characterization of zebrafish ATM International Journal of Biochemistry & Cell Biology  2005 37:1105-1116  DOI:10.1016/j.biocel.2004.10.015  PMID:15743681
    • Kishi, S. Functional aging and gradual senescence in zebrafish Annals of the New York Academy of Sciences  2004 1019:521-526  DOI:10.1196/annals.1297.097  PMID:15247079
    • Kishi, S., Uchiyama, J., Baughman, A. M., Goto, T., Lin, M. C., Tsai, S. B. The zebrafish as a vertebrate model of functional aging and very gradual senescence Experimental Gerontology  2003 38:777-786  DOI:10.1016/s0531-5565(03)00108-6  PMID:12855287
    • Nakamura, M., Zhou, X. Z., Kishi, S., Lu, K. P. Involvement of the telomeric protein Pin2/TRF1 in the regulation of the mitotic spindle FEBS Letters  2002 514:193-198  DOI:10.1016/s0014-5793(02)02363-3  PMID:11943150
    • Kishi, S., Lu, K. P. A critical role for Pin2/TRF1 in ATM-dependent regulation. Inhibition of Pin2/TRF1 function complements telomere shortening, radiosensitivity, and the G(2)/M checkpoint defect of ataxia-telangiectasia cells Journal of Biological Chemistry  2002 277:7420-7429  DOI:10.1074/jbc.M111365200  PMID:11744712
    • Yabu, T., Kishi, S., Okazaki, T., Yamashita, M. Characterization of zebrafish caspase-3 and induction of apoptosis through ceramide generation in fish fathead minnow tailbud cells and zebrafish embryo Biochemical Journal  2001 360:39-47  DOI:10.1042/0264-6021:3600039  PMID:11695990  PMCID:PMC1222200
    • Nakamura, M., Zhou, X. Z., Kishi, S., Kosugi, I., Tsutsui, Y., Lu, K. P. A specific interaction between the telomeric protein Pin2/TRF1 and the mitotic spindle Current Biology  2001 11:1512-1516  DOI:10.1016/s0960-9822(01)00456-0  PMID:11591318
    • Kishi, S., Zhou, X. Z., Ziv, Y., Khoo, C., Hill, D. E., Shiloh, Y., Lu, K. P. Telomeric protein Pin2/TRF1 as an important ATM target in response to double strand DNA breaks Journal of Biological Chemistry  2001 276:29282-29291  DOI:10.1074/jbc.M011534200  PMID:11375976
    • Kishi, S., Wulf, G., Nakamura, M., Lu, K. P. Telomeric protein Pin2/TRF1 induces mitotic entry and apoptosis in cells with short telomeres and is down-regulated in human breast tumors Oncogene  2001 20:1497-1508  DOI:10.1038/sj.onc.1204229  PMID:11313893
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Research

research overview

  • Molecular Genetics and Epigenetics of Aging in Vertebrates

    Our research is focused on increasing our understanding of the molecular basis of aging in vertebrates using zebrafish (Danio rerio), which has now emerged as a powerful vertebrate model system that allows for large-scale genetic and genome-wide approaches to the study of senescence in multiple tissues and organs. Our initial goal is to develop experimental models of aging and geriatric diseases including neurodegenerative disease in zebrafish. A major objective of the our aging research in zebrafish is to develop a high-throughput processing system for gene identification and phenotype characterization particularly associated with age-related disorders in humans to find therapeutic interventions.


    Neurodegeneration and neuromuscular disease both seem to be correlates with aging genetically and epigenetically. These pathological processes are thought to result, at least in part, from the chronic accumulation of reactive oxygen species (ROS) generated through normal cellular metabolism as well as caused from environments. Both genetic background and epigenetic modulations are important determinants of disease susceptibility and impact the process of chronic disease development through gene-gene interactions and gene-environment interactions.


    Our recent report demonstrates the utility of zebrafish in the identification of genes that regulate oxidative stress and aging in vertebrates. Using both N-ethyl-N-nitrosourea (ENU) mutagenesis and retroviral insertion methods to induce genetic mutations in zebrafish embryos, we identified genes that alter the expression of a senescence-associated β-galactosidase under conditions of oxidative stress. Our study shows that biomarkers of stress response in embryos are consistent with neuromuscular degeneration and other advanced aging symptoms in adults since many of the genes identified in the screen also induce aging-related phenotypes in adult zebrafish. Our work demonstrates the potential for zebrafish as a tractable vertebrate model for identification of aging-related genes and their modifiers through their early developmental process in an unbiased fashion and high-throughput manner.

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Background

education and training

  • M.D. in Medicine, Wakayama Medical University
  • Ph.D., Wakayama Medical University
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Contact

full name

  • Shuji Kishi

geographic location

  • Scripps Florida 

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