Richard I. Morimoto
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.[1]
Richard I. Morimoto | |
---|---|
Born | Chicago, Illinois, U.S. | June 9, 1952
Nationality | American |
Alma mater | University of Illinois at Chicago University of Chicago |
Known for | Protein folding Heat shock response Molecular chaperones Neurodegenerative diseases Proteostasis |
Scientific career | |
Fields | Molecular biology Biochemistry |
Institutions | Northwestern University |
Doctoral advisor | Murray Rabinowitz |
Education and academic career
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)[2] 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
- Faculty liaison to founding of the Asian American Studies Program at Northwestern University – March, 1995
- Faculty Advisory Board – Asian American Studies Program at Northwestern University – 1999-
- Midwest Buddhist Temple, Chicago, IL. – Board of Trustees, 2004- ; President, Board of Trustees, 2009 – 2014
- Japanese American Citizens League, Japanese American of the Biennium, 2010
- Chicago Nikkei Forum, 2014-
- Board of Trustees, Japanese American National Museum, 2014-
- Japanese American Leadership Delegation, 2015, U.S.-Japan Council (USJC), Foreign Ministry of Japan
Science
Morimoto is widely recognized for his research on the regulation of the heat shock stress response and the function of molecular chaperones.[3] 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
- American Cancer Society Faculty Research Award, 1987
- Commandeur, Ordre des Palmes Académiques, Ministry of Education, France, 2013[4]
- 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
- Teixeira-Castro, A; Jalles, A; Esteves, S; Kang, S; da Silva Santos, L; Silva-Fernandes, A; Neto, MF; Brielmann, RM; Bessa, C; Duarte-Silva, S; Miranda, A; Oliveira, S; Neves-Carvalho, A; Bessa, J; Summavielle, T; Silverman, RB; Oliveira, P; Morimoto, RI; Maciel, P (2015). "Serotonergic signalling suppresses ataxin 3 aggregation and neurotoxicity in animal models of Machado-Joseph disease". Brain. 138: 3221–37. doi:10.1093/brain/awv262. PMID 26373603.
- Nillegoda, NB; Kirstein, J; Szlachcic, A; Berynskyy, M; Stank, A; Stengel, F; Arnsburg, K; Gao, X; Scior, A; Aebersold, R; Guilbride, DL; Wade, RC; Morimoto, RI; Mayer, MP; Bukau, B (2015). "Crucial HSP70 co-chaperone complex unlocks metazoan protein disaggregation". Nature. 524: 247–51. doi:10.1038/nature14884. PMC 4830470. PMID 26245380.
- Kirstein, J; Morito, D; Kakihana, T; Sugihara, M; Minnen, A; Hipp, MS; Nussbaum-Krammer, C; Kasturi, P; Hartl, FU; Nagata, K; Morimoto, RI (2015). "Proteotoxic stress and ageing triggers the loss of redox homeostasis across cellular compartments". EMBO J. 34: 2334–49. doi:10.15252/embj.201591711. PMC 4570520. PMID 26228940.
- Labbadia, J.; Morimoto, R.I. (2015). "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.
- Walther, DM; Kasturi, P; Zheng, M; Pinkert, S; Vecchi, G; Ciryam, P; Morimoto, RI; Dobson, CM; Vendruscolo, M; Mann, M; Hartl, FU (2015). "Widespread Proteome Remodeling and Aggregation in Aging C. elegans". Cell. 161: 919–32. doi:10.1016/j.cell.2015.03.032. PMC 4643853. PMID 25957690.
- Labbadia, J; Morimoto, RI (2015). "The biology of proteostasis in aging and disease". Annu Rev Biochem. 84: 435–64. doi:10.1146/annurev-biochem-060614-033955. PMC 4539002. PMID 25784053.
- Yu, MS; Kim, BH; Kang, SH; Lim, DJ (2015). "Combined use of crushed cartilage and fibrin sealant for radix augmentation in Asian rhinoplasty". Plast Reconstr Surg. 135: 293e–300e. doi:10.1097/PRS.0000000000001114. PMID 25626813.
- Tatum, MC; Ooi, FK; Chikka, MR; Chauve, L; Martinez-Velazquez, LA; Steinbusch, HW; Morimoto, RI; Prahlad, V (2015). "Neuronal serotonin release triggers the heat shock response in C. elegans in the absence of temperature increase". Curr Biol. 25: 163–74. doi:10.1016/j.cub.2014.11.040. PMC 4840938. PMID 25557666.
- Roth, DM; Hutt, DM; Tong, J; Bouchecareilh, M; Wang, N; Seeley, T; Dekkers, JF; Beekman, JM; Garza, D; Drew, L; Masliah, E; Morimoto, RI; Balch, WE (2014). "Modulation of the maladaptive stress response to manage diseases of protein folding". PLoS Biol. 12: e1001998. doi:10.1371/journal.pbio.1001998. PMC 4236052. PMID 25406061.
- Kennedy, BK; Berger, SL; Brunet, A; Campisi, J; Cuervo, AM; Epel, ES; Franceschi, C; Lithgow, GJ; Morimoto, RI; Pessin, JE; Rando, TA; Richardson, A; Schadt, EE; Wyss-Coray, T; Sierra, F (2014). "Geroscience: linking aging to chronic disease". Cell. 159: 709–13. doi:10.1016/j.cell.2014.10.039. PMC 4852871. PMID 25417146.
- Brehme, M; Voisine, C; Rolland, T; Wachi, S; Soper, JH; Zhu, Y; Orton, K; Villella, A; Garza, D; Vidal, M; Ge, H; Morimoto, RI (2014). "A chaperome subnetwork safeguards proteostasis in aging and neurodegenerative disease". Cell Rep. 9: 1135–50. doi:10.1016/j.celrep.2014.09.042. PMC 4255334. PMID 25437566.
- van Oosten-Hawle, P; Morimoto, RI (2014). "Organismal proteostasis: role of cell-nonautonomous regulation and transcellular chaperone signaling". Genes Dev. 28: 1533–43. doi:10.1101/gad.241125.114. PMC 4102760. PMID 25030693.
- Shibata, Y; Morimoto, RI (2014). "How the nucleus copes with proteotoxic stress". Curr Biol. 24: R463-74. doi:10.1016/j.cub.2014.03.033. PMC 4207067. PMID 24845679.
- Yu, A; Shibata, Y; Shah, B; Calamini, B; Lo, DC; Morimoto, RI (2014). "Protein aggregation can inhibit clathrin-mediated endocytosis by chaperone competition". Proc Natl Acad Sci U S A. 111: E1481-90. doi:10.1073/pnas.1321811111. PMC 3992642. PMID 24706768.
- Ciryam, P.; Tartaglia, G. G.; Morimoto, R. I.; Dobson, C. M.; Vendruscolo, M. (2013). "Neurodegenerative Diseases and Widespread Aggregation are Associated with Supersaturated Proteins". Cell Reports. 5: 781–790. doi:10.1016/j.celrep.2013.09.043.
- Gidalevitz, G.; Wang, N.; Deravaj, T.; Morimoto, R.I. (2013). "Natural Genetic Variation Determines Susceptibility to Aggregation or Toxicity in a C. elegans model for Polyglutamine Disease". BMC Biology. 11: 100. doi:10.1186/1741-7007-11-100.
- Silva, M. C.; Amaral, M. D.; Morimoto, R.I. "Neuronal Reprogramming of Protein Homeostasis by Calcium-Dependent Regulation of the Heat Shock Response". PLoS Genetics. 9 (8): e1003711. doi:10.1371/journal.pgen.1003711.
- Labbadia, J.; Morimoto, R.I. (2013). "Huntington's Disease – Underlying Molecular Mechanisms and Emerging Concepts". Trends in Biochemical Sciences. 38 (8): 378–385. doi:10.1016/j.tibs.2013.05.003. PMC 3955166.
- van Oosten-Hawle, P.; Porter, R.; Morimoto, R. I. (2013). "Regulation of Organismal Proteostasis by Transcellular Chaperone Signaling". Cell. 153: 1366–1378.
- Kirstein-Miles, J; Scior, A; Deuerling, E; Morimoto, RI (2013). "The nascent polypeptide-associated complex is a key regulator of proteostasis". EMBO J. 32: 1451–68. doi:10.1038/emboj.2013.87. PMC 3655472. PMID 23604074.
- Guisbert, E.; Czyz, D. M.; Richter, K.; McMullen, P. D.; Morimoto, R. I. "Identification of a Tissue-Selective Heat Shock Response Regulatory Network". PLoS Genetics. 9 (4): e1003466. doi:10.1371/journal.pgen.1003466.
- Krammer, C.; Park, K.W.; Li, L.; Melki, R.; Morimoto, R.I. "Spreading of a Prion Domain from Cell to Cell by Vesicular Transport in C. elegans". PLoS Genetics. 9 (3): e1003351. doi:10.1371/journal.pgen.1003351.
- Ciryam, P; Morimoto, RI; Vendruscolo, M; Dobson, CM; O'Brien, EP (2013). "In vivo translation rates can substantially delay the cotranslational folding of the Escherichia coli cytosolic proteome". Proc Natl Acad Sci U S A. 110: E132-40. doi:10.1073/pnas.1213624110. PMC 3545769. PMID 23256155.
- Rampelt, H; Kirstein-Miles, J; Nillegoda, NB; Chi, K; Scholz, SR; Morimoto, RI; Bukau, B (2012). "Metazoan Hsp70 machines use Hsp110 to power protein disaggregation". EMBO J. 31: 4221–35. doi:10.1038/emboj.2012.264. PMC 3492728. PMID 22990239.
- Morimoto, RI (2011). "The heat shock response: systems biology of proteotoxic stress in aging and disease". Cold Spring Harb Symp Quant Biol. 76: 91–9. doi:10.1101/sqb.2012.76.010637. PMID 22371371.
- Silva, M. C.; Fox, S.; Thakkar, H.; Beam, M. J. Rivera; Amaral, M. D.; Morimoto, R.I. "A Genetic Screening Strategy Identifies Novel Global Regulators of the Proteostasis Network". PLOS Genetics. 7 (12): e1002438. doi:10.1371/journal.pgen.1002438.
- Calamini, B.; Silva, C.; Madoux, F.; Hutt, D. M.; Khanna, S.; Chalfant, M.; Hodder, P.; Tait, B.; Garza, D.; Balch, W.; Morimoto, R.I. (2012). "Small Molecule Proteostasis Regulators for Protein Conformational Disease". Nature Chemical Biology. 8: 185–196. doi:10.1038/nchembio.763. PMC 3262058.
- Teixeira-Castro, A; Ailion, M; Jalles, A; et al. (August 2011). "Neuron-specific proteotoxicity of mutant ataxin-3 in C. elegans: rescue by the DAF-16 and HSF-1 pathways". Hum. Mol. Genet. 20: 2996–3009. doi:10.1093/hmg/ddr203. PMC 3131043. PMID 21546381.
- Prahlad, V; Morimoto, RI (2011). "Neuronal circuitry regulates the response of Caenorhabditis elegans to misfolded proteins". Proc Natl Acad Sci U S A. 108: 14204–9. doi:10.1073/pnas.1106557108. PMC 3161566. PMID 21844355.
- Gidalevitz, T; Prahlad, V; Morimoto, RI (June 2011). "The stress of protein misfolding: from single cells to multicellular organisms". Cold Spring Harb Perspect Biol. 3: a009704–a009704. doi:10.1101/cshperspect.a009704. PMID 21536706.
- Åkerfelt, M.; Morimoto, R.I.; Sistonen, L. (2010). "Heat Shock Factors: Integrators of Cell Stress, Development, and Lifespan". Nature Reviews Molecular Cell Biology. 11: 545–555. doi:10.1038/nrm2938. PMC 3402356.
- Ben-Zvi-A; Miller, E.A.; Morimoto, R.I. (2009). "The Collapse of Proteostasis Represents an Early Molecular Event in C. elegans Aging". Proc. Natl. Acad. Sci. USA. 106: 14914–14919. doi:10.1073/pnas.0902882106.
- Powers, E.T.; Morimoto, R.I.; Dillin, A.; Kelly, J.W.; Balch, W.E. (2009). "Biological and Chemical Approaches to Diseases of Proteostasis Deficiency". Annual Review of Biochemistry. 78: 959–991. doi:10.1146/annurev.biochem.052308.114844.
- Westerheide, S.D.; Anckar, J.; Stevens, S.; Sistonen, L.; Morimoto, R.I. (2009). "Stress-Inducible Regulation of Heat Shock Factor 1 by the Deacetylase SIRT1". Science. 323: 1063–1066. doi:10.1126/science.1165946. PMC 3429349.
- Prahlad, V.; Cornelius, T.; Morimoto, R.I. (2008). "Regulation of the Cellular Heat Shock Response in Caenorhabditis elegans by Thermosensory Neurons". Science. 320: 811–814. doi:10.1126/science.1156093. PMC 3429343.
- Balch, W. E.; Morimoto, R.I.; Dillin, A.; Kelly, J. W. (2008). "Adapting Proteostasis for Disease Intervention". Science. 319: 916–919. doi:10.1126/science.1141448.
- Morimoto, R.I. (2008). "Proteotoxic Stress and Inducible Chaperone Networks in Neurodegenerative Disease and Aging". Genes & Development. 22: 1427–1438. doi:10.1101/gad.1657108.
- Garcia, S.; Casanueva, M.O.; Silva, C.; Amaral, M.; Morimoto, R.I. (2007). "Neuronal Signaling Modulates Protein Homeostasis in Caenorhabditis elegans Postsynaptic Muscle Cells". Genes & Development. 21: 3006–3016. doi:10.1101/gad.1575307.
- Brignull, H.; Moore, F.; Tang, S.; Morimoto, R.I. (2006). "Polyglutamine Proteins at the Pathogenic Threshold Display Neuron-Specific Aggregation in a Pan-Neuronal C. elegans Model". Journal of Neuroscience. 26: 7597–7606. doi:10.1523/jneurosci.0990-06.2006.
- Gidalevitz, T.; Ben-Zvi, A.; Ho, K.; Brignull, H.; Morimoto, R.I. (2006). "Progressive Disruption of Cellular Protein Folding in Models of Polyglutamine Diseases ". Science. 311: 1471–1474. doi:10.1126/science.1124514.
- Holmberg, C.; Staniszewski, K.; Mensah, K.; Chavez, A.; Matouschek, A.; Morimoto, R.I. (2004). "Inefficient Degradation of Truncated Polyglutamine Proteins by the Proteasome". EMBO Journal. 23: 4307–4318. doi:10.1038/sj.emboj.7600426. PMC 524390.
- Morley, J.F.; Morimoto, R.I. (2004). "Regulation of Longevity in C. elegans by Heat Shock Factor and Molecular Chaperones". Mol. Biol. Cell. 15: 657–664. doi:10.1091/mbc.e03-07-0532. PMC 329286.
- Morimoto, R.I. (2002). "Dynamic Remodeling of Transcription Complexes by Molecular Chaperones". Cell. 110: 281–284. doi:10.1016/s0092-8674(02)00860-7.
- Kim, S.; Nollen, E.A.A.; Kitagawa, K.; Bindokas, V.; Morimoto, R.I. (2002). "Polyglutamine Protein Aggregates are Dynamic". Nature Cell Biology. 4: 826–831. doi:10.1038/ncb863.
- 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). doi 10.1073/pnas.152161099
- Shen, X.; Ellis, R.E.; Lee, K.; Liu, C.-Y.; Yang, K.; Solomon, A.; Yoshida, H.; Morimoto, R.; Kurnit, D.M.; Mori, K.; Kaufman, R.J. (2001). "Complementary Signaling Pathways Regulate the Unfolded Protein Response and Are Required for C. elegans Development". Cell. 107: 893–903. doi:10.1016/s0092-8674(01)00612-2.
- Song, J.; Takeda, M.; Morimoto, R.I. (2001). "Hsp70-Bag1 Complex Mediates a Physiological Stress Signaling Pathway that Regulates Raf-1/Erk and Cell Growth". Nature Cell Biology. 3: 276–282. doi:10.1038/35060068.
- Thress, K.; Song, J.; Morimoto, R.I.; Kornbluth, S. "Reversible Inhibition of Hsp70 Chaperone Function by Scythe and Reaper". EMBO Journal. 20: 103–1041.
- Satyal, S.; Schmidt, E.; Kitagawa, K.; Sondheimer, N.; Lindquist, S.; Morimoto, R.I. (2000). "Polyglutamine Aggregates Alter Protein Folding Homeostasis in C. elegans". Proc. Natl. Acad. Sci. USA. 97: 5750–5755. doi:10.1073/pnas.100107297.
- Shi, Y. D. Mosser; Morimoto, R.I. (1998). "Molecular Chaperones as HSF1 Specific Transcriptional Repressors". Genes & Development. 12: 654–666. doi:10.1101/gad.12.5.654.
- Morimoto, R.I. (1998). "Regulation of the Heat Shock Transcriptional Response: Crosstalk between a Family of Heat Shock Factors, Molecular Chaperones, and Negative Regulators". Genes & Development. 12: 3788–3796. doi:10.1101/gad.12.24.3788.
- Kanei-Ishii, C. Tanikawa J. Nakai A. Morimoto R.I.; Ishii, S. (1997). "Activation of heat shock transcription factor 3 by c-Myb in the absence of cellular stress". Science. 277 (5323): 246–8. doi:10.1126/science.277.5323.246.
- Freeman, B.C.; Toft, D.; Morimoto, R.I.; Chaperone Machines, Molecular (1996). "Chaperone Activities of the Cyclophilin CyP-40 and the Steroid Aporeceptor Associated Protein p23". Science. 274: 1718–1720. doi:10.1126/science.274.5293.1718.
- Freeman, B.C.; Morimoto, R.I. (1996). "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. doi:10.1002/j.1460-2075.1996.tb00660.x.
- Lee, B.; Chen, J.; Jurivich, D.; Angelidis, C.; Morimoto, R.I. (1995). "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. doi:10.1073/pnas.92.16.7207.
- Abravaya, K.; Myers, M.; Murphy, S.; Morimoto, R.I. (1992). "Human Heat Shock Protein HSP70 Interacts with HSF, the Transcription Factor That Regulates Heat Shock Gene Expression". Genes & Development. 6: 1153–1164. doi:10.1101/gad.6.7.1153.
- Jurivich, D.; Sistonen, L.; Kroes, R.; Morimoto, R.I. (1992). "Effects of Sodium Salicylate on the Human Heat Shock Response". Science. 255: 1243–1245. doi:10.1126/science.1546322.
- Abravaya, K.; Phillips, B.; Morimoto, R.I. (1991). "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. doi:10.1101/gad.5.11.2117.
- Sarge, K.; Zimarino, V.; Holm, K.; Wu, C.; Morimoto, R.I. (1991). "Cloning and Characterization of Two Mouse Heat Shock Transcription Factors with Distinct Inducible and Constitutive DNA Binding Ability". Genes & Development. 5: 1902–1911. doi:10.1101/gad.5.10.1902.
- Wu, B.; Hunt, C.; Morimoto, R.I. (1985). "The Structure and Expression of the Human Gene Encoding the Major Heat Shock Protein HSP70". Mol. Cell. Biol. 5: 330–341. doi:10.1128/mcb.5.2.330.
In pop culture
In a YouTube video[5] 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.
References
- "A Conversation with Richard Morimoto". Cold Spring Harbor Symposia on Quantitative Biology. 80: 336–337. 2015-01-01. doi:10.1101/sqb.2015.80.030031. ISSN 0091-7451. PMID 27325725.
- Limited, The Company of Biologists (2014-01-01). "Creating a path from the heat shock response to therapeutics of protein-folding diseases: an interview with Rick Morimoto". Disease Models & Mechanisms. 7 (1): 5–8. doi:10.1242/dmm.014753. ISSN 1754-8403. PMC 3882042. PMID 24396148.
- "Professor Richard Morimoto - Proteostasis Symposium 2017". Proteostasis Symposium 2017. Retrieved 2018-08-01.
- "Professor Richard Morimoto awarded Les Palmes Académiques". Consulat Général de France à Chicago. Retrieved 2018-08-01.
- https://www.youtube.com/watch?v=c-86OQgcMTM