Richard I. Morimoto

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Richard I. Morimoto
Born (1952-06-09) June 9, 1952 (age 65)
Chicago, Illinois, U.S.
Residence Evanston, Illinois, U.S.
Nationality American
Fields Molecular biology
Biochemistry
Institutions Northwestern University
Alma mater University of Illinois at Chicago
University of Chicago
Doctoral advisor Murray Rabinowitz
Known for Protein folding
Heat shock response
Molecular chaperones
Neurodegenerative diseases
Proteostasis

Richard I. Morimoto (born June 9, 1952) is a Japanese American molecular biologist. He is the Bill and Gayle Cook Professor of Biology and Director of the Rice Institute for Biomedical Research at Northwestern University.

Education and academic career[edit]

He holds a B.S. from the University of Illinois at Chicago, received a Ph.D. in Biology (laboratory of Professor Murray Rabinowitz) from the University of Chicago in 1978, and conducted postdoctoral research (laboratory of Professor Matthew Meselson) and was a Tutor in Biochemical Sciences at Harvard University in Cambridge, MA. In 1982, Morimoto joined the faculty of the Department of Biochemistry, Molecular Biology, and Cell Biology at Northwestern University in Evanston, IL. He served previously as the Chair of Biochemistry, Molecular Biology, and Cell Biology, the Dean of The Graduate School, and the Associate Provost of Graduate Education at Northwestern University.

Civic leadership[edit]

Science[edit]

Morimoto is widely recognized for his research on the regulation of the heat shock stress response and the function of molecular chaperones. His current research is to understand how organisms sense and respond to physiologic and environmental stress through the activation of genetic pathways that integrate stress responses with molecular and cellular responses that determine cell growth and cell death. The stress of misfolded and damaged proteins influences neuronal function and lifespan at the level of the organism. Consequently, these studies provide a molecular basis to elucidate the underlying mechanisms of neurodegenerative diseases including Huntington's disease, Parkinson's disease, ALS, and Alzheimer's disease. His laboratory has published over 250 papers and three monographs including two books on the Heat Shock Response and Molecular Chaperones from Cold Spring Harbor Press. During that period he received two MERIT awards from the National Institutes of Health and has been supported by the grants from the National Institutes for General Medical Science, National Institutes of Aging, National Institutes for Neurological Diseases and Stroke, American Cancer Society, Huntington's Disease Society of America, the Hereditary Disease Foundation, and the ALS Association. In addition to giving frequent talks at universities and scientific symposia throughout the world, he has been a Visiting Professor at the Technion University in Israel, Osaka University, Kyoto University, Kyoto Sangyo University, University of Rome, Beijing University, Åbo Akademi University in Finland, and École Normale Supérieure in Paris. He is a founder of Proteostasis Therapeutics, Inc. in Cambridge, MA, a biotech company that is discovering and developing novel small molecule therapeutics designed to control the body’s protein homeostasis. These novel therapies are designed to treat multiple degenerative disorders such as Alzheimer’s disease, Parkinson's disease, Huntington’s disease, cancer, and type II diabetes.

Science recognition[edit]

  • American Cancer Society Faculty Research Award, 1987
  • Commandeur, Ordre des Palmes Académiques, Ministry of Education, France, 2013
  • Doctor of Philosophy, Honoris Causa – Abo Akademi University, Turku, Finland, 2008
  • Dreyfus Distinguished Young Faculty Award, 1982
  • Elected Fellow of the American Academy of Arts and Sciences, 2011
  • Elected Fellow of the American Association for the Advancement of Science, 1998
  • Feodor Lynen Medal, German Society for Biochemistry and Molecular Biology, 2014
  • National Institutes of Health Merit Award - National Institute for General Medical Science (2000), National Institute on Aging (2011)
  • Huntington's Disease Society of America, Award for Excellence in Medicine, 2005
  • Japan Society for the Promotion of Science Fellow, 2015
  • University of Illinois, Alumni Achievement Award, 2011

Significant papers[edit]

  • Teixeira-Castro, A., A. Jalles, S. Esteves, S. Kang, L. da Silva Santos, A. Silva-Fernands, M.F. Neto, R.M. Brielmann, C. Bessa, S. Duaret-Silva, A. Miranda, S. Oliveira, A. Neves-Carvalho, J. Bessa, T. Summavielle, R.B. Silverman, P. Oliveria, R.I. Morimoto, and P. Maciel. Sertonergic Signaling Suppresses Ataxin-3 Aggregation and Neurotoxicity in Animal Models of Machado-Joseph Disease. Brain, PMID 26373603 (2015).
  • Nillegoda, N.B., J. Kirstein, A. Szlachcic, M. Berynskyy, A. Stank, F. Stenge4, K. Arnsburg, X. Gao, R. Aebersold, D.L. Guilbride, R.C. Wade, R.I. Morimoto, M.P. Mayer, and B. Bukau. Crucial Hsp70 Co-chaperone Complex Unlocks Metazoan Protein Disaggregation. Nature 524: 247-251, DOI: 10.1038/nature14884, PMID 26245380 (2015).
  • Kirstein, J., D. Morito, T. Kakihana, M. Sugihara, A. Minnen, M.S. Hipp, C. Nussbaum-Krammer, F.U. Hartl, K. Nagata, and R.I. Morimoto. Proteotoxic Stress and Ageing Triggers the Loss of Redox Homeostasis Across Cellular Compartments. EMBO Journal 34: 2334-2349, PMID 26228940 (2015).
  • Labbadia, J. and R.I. Morimoto. Repression of the Heat Shock Response is a Programmed Event at the Onset of Reproduction. Molecular Cell 59: 639-650, DOI 10.1016/j.molcel.2015.06.027 (2015).
  • Walther, D.M., P. Kasturi, M. Zheng, S. Pinkert, G. Vecchi, P. Ciryam, R.I. Morimoto, C.M. Dobson, M. Vendruscolo, M. Mann and F.-U. Hartl. Widespread Proteome Remodeling and Aggregation in Aging C. elegans. Cell 161(4): 919-932, DOI: 10.1016/j.cell.2015.03.032, PMID 25957690 (2015).
  • Labbadia, J., and R.I. Morimoto. The Biology of Proteostasis in Aging and Disease. Annual Reviews of Biochemistry 84: 435-464, DOI: 10.1146/annurev-biochem-060614-033955, PMID 25784053 (2015).
  • Ciryam, P., R. Kundra, R. I. Morimoto, C. M. Dobson, and M. Vendruscolo. Supersaturation is a Driving Force for Protein Aggregation in Neurodegenerative Diseases. Trends in Pharmacological Sciences, 36: 72-77, DOI:10.1016/j.tips.2014.12.004, PMID 25626813 (2015).
  • Tatum, M.C., M.D. Chikka, F.K. Oi, L. Chauve, L.A. Martinez-Velazquez, H.W.M. Steinbusch, R.I. Morimoto, and V. Prahlad. Optogenetic Stimulation of Serotonin Release Activates the Heat Shock Response in Distal Tissues of C. elegans. Current Biology 25: 163-174, DOI: 10.1016/j.cub.2014.11.040, PMID 25557666 (2015).
  • Roth, D. M., D.M. Hutt, J. Tong, M. Bouchecareih, N. Wang, D. Garza, R.I. Morimoto, and W.E. Balch. Correcting Misfolding Disease by Managing the Maladaptive Stress Response. PLoS Biology 12: e1001998, PMID 25406061 (2014).
  • Kennedy, B.K., S.L. Berger, A. Brunet, J. Campisi, A.M. Cuervo, E.S. Epel, C. Franceschi, G.J. Lithgow, R.I. Morimoto, J.E. Pessin, T.A. Rando, A. Richardson, E.E. Schadt, T. Wyss-Coray, and F. Sierra. Geroscience: Linking Aging to Disease. Cell 159: 709-713, PMID 25417146 (2014).
  • Brehme, M., C. Voisine, T. Rolland, S. Wachi, J. Soper, Y. Zhu, K. Orton, A. Villella, D. Garza, M. Vidal, H. Ge, and R.I. Morimoto. A Conserved Chaperome Sub-Network Safeguards Protein Homeostasis in Aging and Neurodegenerative Disease. Cell Reports 9: 1135–1150, doi:10.1016/j.celrep.2014.09.042, PMC 4255334, PMID 25437566 (2014).
  • Van Oosten-Hawle, P., and R.I. Morimoto. Organismal Control of Proteostasis by Cell Non-Autonomous Regulation and Transcellular Stress Signaling. Genes and Development 28: 1533-1543, DOI: 10.1101/gad.241125.114, PMID 25030693 (2014).
  • Shibata, Y., and R.I. Morimoto. How the Nucleus Copes with Proteotoxic Stress. Current Biology 24: R463-474, DOI: 10.1016/j.cub.2014.03.033, PMID 24845679 (2014).
  • Yu, A., Y. Shibata, B. Shah, B. Calamini, D. Lo, and R.I. Morimoto. Protein Aggregation Inhibits Clathrin-Mediated Endocytosis by Chaperone Competition. Proc. Natl. Acad. Sci. USA PMID 24706768 DOI: 10.1073 (2014).
  • Ciryam, P., G. G. Tartaglia, R. I. Morimoto, C. M. Dobson, and M. Vendruscolo. Neurodegenerative Diseases and Widespread Aggregation are Associated with Supersaturated Proteins. Cell Reports 5: 781-790, DOI: 10.1016 (2013).
  • Gidalevitz, G., N. Wang, T. Deravaj, and R.I. Morimoto. Natural Genetic Variation Determines Susceptibility to Aggregation or Toxicity in a C. elegans model for Polyglutamine Disease. BMC Biology 11, 100, DOI: 10.1186 (2013).
  • Silva, M. C., M. D. Amaral, and R.I. Morimoto. Neuronal Reprogramming of Protein Homeostasis by Calcium-Dependent Regulation of the Heat Shock Response. PLoS Genetics 9(8), DOI: 10.1371, e1003711 (2013).
  • Labbadia, J., and R.I. Morimoto. Huntington’s Disease – Underlying Molecular Mechanisms and Emerging Concepts. Trends in Biochemical Sciences 38(8): 378-385, DOI:10.1016 (2013).
  • van Oosten-Hawle, P., R. Porter, and R. I. Morimoto. Regulation of Organismal Proteostasis by Transcellular Chaperone Signaling. Cell 153: 1366-1378, DOI:10.1016 (2013).
  • Kirstein-Miles, J., A. Scior, E. Duerling, and R.I. Morimoto. The Nascent Polypeptide Associated Complex is a Key Regulator of Proteostasis. The EMBO Journal PMID 23604074 DOI: 10.1038 (2013).
  • Guisbert, E., D. M. Czyz, K. Richter, P. D. McMullen, and R. I. Morimoto. Identification of a Tissue-Selective Heat Shock Response Regulatory Network. PLoS Genetics 9(4): DOI: 10.1371 (2013).
  • Krammer, C., K.W. Park, L. Li, R. Melki, and R.I. Morimoto. Spreading of a Prion Domain from Cell to Cell by Vesicular Transport in C. elegans. PLoS Genetics 9(3): DOI: 10.1371 (2013).
  • Ciryam, C., R. I. Morimoto, M. Vendruscolo, C. M. Dobson, and E. P. O’Brien. In vivo Translation Rates can Substantially Delay the Co-Translational Folding of the E. coli Cytosolic Proteome. Proc. Natl. Acad. Sci. USA 110: E132-140, PMID 23256155 (2013).
  • Rampelt, H., J. Kirstein-Miles, S. Scholz, N. Nillegoda, R.I. Morimoto, B. Bukau. Metazoan Hsp70 Machines use Hsp110 to Power Protein Disaggregation. The EMBO Journal 31(21): 4221-35. PMID 22990239 (2012).
  • Morimoto, R.I. The Heat Shock Response: Systems Biology of Proteotoxic Stress in Aging and Disease. Cold Spring Harbor Symposia on Quantitative Biology Volume LXXVI: Metabolism and Disease. Cold Spring Harbor Press, p. 91-99, PMID 22371371 (2012).
  • Silva, M. C., S. Fox, H. Thakkar, M. J. Rivera Beam, M. D. Amaral, and R.I. Morimoto. A Genetic Screening Strategy Identifies Novel Global Regulators of the Proteostasis Network. PloS Genetics.7(12): (2011).
  • Calamini, B., C. Silva, F. Madoux, D. M. Hutt, S. Khanna, M. Chalfant, P. Hodder, B. Tait, D. Garza, W. Balch, and R.I. Morimoto. Small Molecule Proteostasis Regulators for Protein Conformational Disease. Nature Chemical Biology (2011).
  • Teixeira-Castro, A., M. Ailion, A. Jalles, H. R. Brignull, J. L. Vilaça, N. Dias, P. Rodrigues, J. F. Oliveira, A. Neves-Carvalho, R. I. Morimoto, and P. Maciel. Neuron-Specific Proteotoxicity of Mutant Ataxin-3 in C. elegans: Rescue by the DAF-16 and HSF1 Pathways. Human Molecular Genetics 20(15): 2996-3009, PMID 21546381 (2011).
  • Prahlad, V. and R.I. Morimoto. Neuronal Circuitry Regulates the Response of C. elegans to Misfolded Proteins. Proc. Natl. Acad. Sci. U.S.A. 108: 14204-14209, PMID 21844355 (2011).
  • Gidalevitz, T., V. Prahlad, and R. I. Morimoto. The Stress of Protein Misfolding: From Single Cells to Multicellular Organisms. Cold Spring Harbor Perspectives in Biology, 3: PMID 21536706 (2011).
  • Åkerfelt, M., R.I. Morimoto, and L. Sistonen. Heat Shock Factors: Integrators of Cell Stress, Development, and Lifespan. Nature Reviews Molecular Cell Biology, 11: 545-555 (2010).
  • Ben-Zvi-A., E.A. Miller, and R.I. Morimoto. The Collapse of Proteostasis Represents an Early Molecular Event in C. elegans Aging. Proc. Natl. Acad. Sci. USA. 106: 14914-14919 (2009).
  • Powers, E.T., R.I. Morimoto, A. Dillin, J.W. Kelly, and W.E. Balch. Biological and Chemical Approaches to Diseases of Proteostasis Deficiency. Annual Reviews of Biochemistry 78: 959-991 (2009).
  • Westerheide, S.D., J. Anckar, S. Stevens, L. Sistonen, and R.I. Morimoto. Stress-Inducible Regulation of Heat Shock Factor 1 by the Deacetylase SIRT1. Science 323: 1063-1066 (2009).
  • Prahlad, V., T. Cornelius and R.I. Morimoto. Regulation of the Cellular Heat Shock Response in Caenorhabditis elegans by Thermosensory Neurons. Science 320: 811-814 (2008).
  • Balch, W. E., R.I. Morimoto, A. Dillin, and J. W. Kelly. Adapting Proteostasis for Disease Intervention. Science 319: 916-919 (2008).
  • Morimoto, R.I. Proteotoxic Stress and Inducible Chaperone Networks in Neurodegenerative Disease and Aging. Genes and Development 22: 1427-1438 (2008).
  • Garcia, S., M.O. Casanueva, C. Silva, M. Amaral, and R.I. Morimoto. Neuronal Signaling Modulates Protein Homeostasis in Caenorhabditis elegans Postsynaptic Muscle Cells. Genes and Development: 21: 3006-3016 (2007).
  • Brignull, H., F. Moore, S. Tang and R.I. Morimoto. Polyglutamine Proteins at the Pathogenic Threshold Display Neuron-Specific Aggregation in a Pan-Neuronal C. elegans Model. J. Neuroscience 26: 7597-7606 (2006).
  • Gidalevitz, T., A. Ben-Zvi, K. Ho, H. Brignull and R.I. Morimoto. Progressive Disruption of Cellular Protein Folding in Models of Polyglutamine Diseases . Science 311: 1471-1474 (2006).
  • Holmberg, C., K. Staniszewski, K. Mensah, A. Chavez, A. Matouschek, and R.I. Morimoto. Inefficient Degradation of Truncated Polyglutamine Proteins by the Proteasome. EMBO Journal 23: 4307-4318 (2004).
  • Morley, J.F. and R.I. Morimoto. Regulation of Longevity in C. elegans by Heat Shock Factor and Molecular Chaperones. Mol. Biol. Cell 15: 657-664 (2004).
  • Morimoto, R.I. Dynamic Remodeling of Transcription Complexes by Molecular Chaperones. Cell 110: 281-284 (2002).
  • Kim, S., E.A.A. Nollen, K. Kitagawa, V. Bindokas and R.I. Morimoto. Polyglutamine Protein Aggregates are Dynamic. Nature Cell Biology 4: 826-831 (2002).
  • Morley J.F., Brignull H.R., Weyers J.J. and R.I. Morimoto. The threshold for polyglutamine-expansion protein aggregation and cellular toxicity is dynamic and influenced by aging in Caenorhabditis elegans. Proc Natl Acad Sci U S A. (2002).
  • Shen, X., R.E. Ellis, K. Lee, C.-Y. Liu, K. Yang, A. Solomon, H. Yoshida, R. Morimoto, D.M. Kurnit, K. Mori and R.J. Kaufman. Complementary Signaling Pathways Regulate the Unfolded Protein Response and Are Required for C. elegans Development. Cell 107: 893-903 (2001).
  • Song, J., M. Takeda, and R.I. Morimoto. Hsp70-Bag1 Complex Mediates a Physiological Stress Signaling Pathway that Regulates Raf-1/Erk and Cell Growth. Nature Cell Biology 3: 276-282 (2001).
  • Thress, K., J. Song, R.I. Morimoto and S. Kornbluth. Reversible Inhibition of Hsp70 Chaperone Function by Scythe and Reaper. EMBO Journal 20: 103-1041 (2001).
  • Satyal, S., E. Schmidt, K. Kitagawa, N. Sondheimer, S. Lindquist and R.I. Morimoto. Polyglutamine Aggregates Alter Protein Folding Homeostasis in C. elegans. Proc. Natl. Acad. Sci. USA. 97: 5750-5755 (2000).
  • Shi, Y. D. Mosser and R.I. Morimoto. Molecular Chaperones as HSF1 Specific Transcriptional Repressors. Genes and Development 12: 654-666 (1998).
  • Morimoto, R.I. Regulation of the Heat Shock Transcriptional Response: Crosstalk between a Family of Heat Shock Factors, Molecular Chaperones, and Negative Regulators. Genes and Development 12: 3788-3796 (1998).
  • Kanei-Ishii C. Tanikawa J. Nakai A. Morimoto R.I. and S. Ishii. Activation of heat shock transcription factor 3 by c-Myb in the absence of cellular stress. Science. 277(5323):246-8, 1997.
  • Freeman, B.C., D. Toft and R.I. Morimoto. Molecular Chaperone Machines: Chaperone Activities of the Cyclophilin CyP-40 and the Steroid Aporeceptor Associated Protein p23. Science 274: 1718-1720 (1996).
  • Freeman, B.C. and R.I. Morimoto. The Human Molecular Chaperones HSP90, HSP70 (HSC70) and HDJ-1 have Distinct Roles in Recognition of a Non-native Protein and Protein Refolding. EMBO Journal 15: 2969-2979 (1996).
  • Lee, B., J. Chen, D. Jurivich, C. Angelidis and R.I. Morimoto. Pharmacological Modulation of the Heat Shock Factor Activity by Anti-Inflammatory Drugs Protects Against Stress-Induced Cellular Damage. Proc. Natl. Acad. Sci. USA 92: 7207-7211 (1995).
  • Abravaya, K., M. Myers, S. Murphy and R.I. Morimoto. Human Heat Shock Protein HSP70 Interacts with HSF, the Transcription Factor That Regulates Heat Shock Gene Expression. Genes and Development 6, 1153-1164 (1992).
  • Jurivich, D., L. Sistonen, R. Kroes and R.I. Morimoto. Effects of Sodium Salicylate on the Human Heat Shock Response. Science 255, 1243-1245 (1992).
  • Abravaya K., Phillips B. and R.I. Morimoto. Attenuation of the heat shock response in HeLa cells is mediated by the release of bound heat shock transcription factor and is modulated by changes in growth and in heat shock temperatures. Genes & Development. 5(11):2117-27, 1991.
  • Sarge, K., V. Zimarino, K. Holm, C. Wu and R.I. Morimoto. Cloning and Characterization of Two Mouse Heat Shock Transcription Factors with Distinct Inducible and Constitutive DNA Binding Ability. Genes and Development 5, 1902-1911 (1991).
  • Wu, B., C. Hunt and R.I. Morimoto. The Structure and Expression of the Human Gene Encoding the Major Heat Shock Protein HSP70. Mol. Cell. Biol. 5, 330-341 (1985).

In pop culture[edit]

In a Youtube video[1] published in 2009, members of the Morimoto lab showed C. elegans forming a smiley face on a culture plate. The video description jokes that when a post doc in the lab told them to smile, the C. elegans, lacking faces as individuals, formed the smiley face as a group, suggesting that they are intelligent, have ears, and can work in groups. In reality, the footage is playing in reverse: the C. elegans were placed into that formation on the plate by a human and then crawled away. By reversing the footage, it looks like the C. elegans spontaneously form a smiley face. The video manipulation is hinted at in the description that reminds the viewers that the YFP is brighter in the individuals' head than their tails.

External links[edit]

References[edit]