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Richard I. Morimoto

Richard I. Morimoto

Bill and Gayle Cook Professor
Molecular Biosciences
PhD, University of Chicago

Email: r-morimoto@northwestern.edu
Phone: (847) 491-3340
Fax: (847) 491-4461
Room: Cook 3129

 

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Research Interests

Chaperone Networks and Mechanisms of Protein Conformational Disease

The research in the Morimoto laboratory addresses: (1) How the stress of misfolded proteins leads to the neurodegenerative disorders Huntington's disease, Parkinson's disease, Alzheimer's disease, and Amyotrophic Lateral Sclerosis. We are interested in the capacity and specificity of the protein quality control machinery to recognize misfolded and aggregation-prone proteins and the role of molecular chaperones and degradative machines in the triage clearance mechanism. We have established C. elegans transgenic lines expressing polyglutamine proteins (Huntingtin and Ataxin 3), mutant SOD1, tau, and prions to screen for modifiers and suppressors and to establish the basis of neuronal cell-type specificity. We have identified a molecular link between the insulin signaling pathway, accumulation of damaged proteins, and regulation of the heat shock response and chaperones revealing that genes that control longevity also suppress protein misfolding. The identification of the protein quality control proteome thus forms the basis for a new class of therapeutics targeting HSF1 and molecular chaperones for neurodegenerative diseases of aging, (2) Transcriptional regulation of the heat shock response. The role of stress sensors that control HSF1 activation during acute stress and recovery, during aging in response to neurohormonal stress signaling molecules, and as a general regulator of protein homeostasis and suppressor of misfolded proteins, and (3) Systems approach to stress biology. Establishing an organism-wide understanding of chaperone network integration of environmental and physiological stress in C. elegans using genetics, molecular, and informatic tools.

Selected Publications

Protein aggregation can inhibit clathrin-mediated endocytosis by chaperone competition. Yu A, Shibata Y, Shah B, Calamini B, Lo DC, and Morimoto RI. PNAS. 2014 April 15;111(15):E1481-E1490.

Dysregulation of the proteasome increases the toxicity of ALS-linked mutant SOD1. Kitamura A, Inada N, Kubota H, Matsumoto G, Kinjo M, Morimoto RI, and Nagata K. Genes to Cells. 2014 March;19(3):209-224.

Transcellular chaperone signaling: an organismal strategy for integrated cell stress responses. van Oosten-Hawle P and Morimoto RI. Journal of Experimental Biology. 2014 January 1;217(1):129-136.

Widespread Aggregation and Neurodegenerative Diseases Are Associated with Supersaturated Proteins. Ciryam P, Tartaglia GG, Morimoto RI, Dobson CM, and Vendruscolo M. Cell Reports. 2013 November 14;5(3):781-790.

Natural genetic variation determines susceptibility to aggregation or toxicity in a C. elegans model for polyglutamine disease. Gidalevitz T, Wang N, Deravaj T, Alexander-Floyd J, and Morimoto RI. BMC Biology. 2013 September;11:100.

Neuronal Reprograming of Protein Homeostasis by Calcium-Dependent Regulation of the Heat Shock Response. Silva MC, Amaral MD, and Morimoto RI. PLoS Genetics. 2013 August 29;9(8):e1003711.

Heat Shock Response Activation Exacerbates Inclusion Body Formation in a Cellular Model of Huntington Disease. Bersuker K, Hipp MS, Calamini B, Morimoto RI, and Kopito RR. Journal of Biological Chemistry. 2013 August 16;288(33):23633-23638.

Regulation of Organismal Proteostasis by Transcellular Chaperone Signaling. van Oosten-Hawle P, Porter RS, and Morimoto RI. Cell. 2013 June 6;153(6):1366-1378.

The nascent polypeptide-associated complex is a key regulator of proteostasis. Kirstein-Miles J, Scior A, Deuerling E, and Morimoto RI. EMBO Journal. 2013 May 15;32(10):1451-1468.

Identification of a Tissue-Selective Heat Shock Response Regulatory Network. Guisbert E, Czyz DM, Richter K, McMullen PD, and Morimoto RI. PLoS Genetics. 2013 April 18;9(4):e1003466.

View all publications by Richard I. Morimoto listed in the National Library of Medicine (PubMed). Current and former IBiS students in blue.