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Shuji Kishi, M.D., Ph.D.

Associate Professor
Department of Molecular Medicine
Florida Campus
Scripps VIVO Scientific Profile
kishi@scripps.edu
(561) 228-2959

Scripps Research Joint Appointments

Faculty, Graduate Program

Other Joint Appointments

Adjunct Professor, Center for Biology & Biotechnology, Florida Atlantic University

Research Focus

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.

Education

M.D., Medicine, Wakayama Medical University
Ph.D., Wakayama Medical University

Professional Experience

2015-2017 Associate Professor, Metabolism and Aging, The Scripps Research Institute
2009-2015 Assistant Professor, Metabolism and Aging, The Scripps Research Institute

Awards & Professional Activities

A-T Children’s Project Research Award (2002, 2005)
Ellison Medical Foundation New Scholar Award in Aging (2003)
Glenn Award for Research in Biological Mechanisms of Aging (2008)
Reviewer of Motor Neuron Disease Association in the United Kingdom
NIGMS/NIH Reviewer for the Minority Biomedical Research Support (MBRS)
Grants at National Institute of General Medical Sciences (NIGMS)
Member of National Scientific Advisory Council (NSAC) in American Federation for Aging Research (AFAR)
Member of Editorial Board, Open Longevity Science

Selected References

All Publications

Imamura, S., Uchiyama, J., Koshimizu, E., Hanai, J., Raftopoulou, C., Murphey, R. D., Bayliss, P. E., Imai, Y., Burns, C. E., Masutomi, K., Gagos, S., Zon, L. I. Roberts, T. M., Kishi, S. (2008). A non-canonical function of zebrafish telomerase reverse transcriptase is required for developmental hematopoiesis. PLoS ONE 3, e3364.

Kishi, S., Bayliss, P. E., Uchiyama, J., Koshimizu, E., Qi, J., Nanjappa, P., Imamura, S., Islam, A., Neuberg, D., Amsterdam, A., and Roberts, T. M. (2008). The identification of zebrafish mutants showing alterations in senescence-associated biomarkers. PLoS Genet 4, e1000152. (Featured by RESEARCH HIGHLIGHTS (2008). Stress response and aging: zebrafish screens identify genes involved in aging. Dis Model Mech 1, 70-71.)

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., D'Andrea, A. A., Look, A. T. (2008). Chk1 suppresses a caspase-2 apoptotic response to DNA damage that bypasses p53, Bcl-2, and caspase-3. Cell 133, 864-877.

Hanai, J., Cao, P., Tanksale, P., Imamura, S., Koshimizu, E., Zhao, J., Kishi, S., Yamashita, M., Phillips, P. S., Sukhatme, V. P., and Lecker, S. H. (2007). The muscle-specific ubiquitin ligase atrogin-1/MAFbx mediates statin-induced muscle toxicity. J Clin Invest 117, 3940-3951.

Links

Department of Metabolism & Aging

The Identification of Zebrafish Mutants Showing Alterations in Senescence-Associated Biomarkers

A Non-Canonical Function of Zebrafish Telomerase Reverse Transcriptase Is Required for Developmental Hematopoiesis

Stress response and aging: zebrafish screens identify genes involved in aging