Faculty
Richard I. Morimoto, PhD
Professor
Molecular Biosciences
PhD, University of Chicago
Email: r-morimoto@northwestern.edu
Phone: (847) 491-3340
Fax: (847) 491-3340
Room: Cook Rm 3129
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. 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
Collapse of proteostasis represents an early molecular event in Caenorhabditis elegans aging. Ben-Zvi A, Miller EA, Morimoto RI. Proc Natl Acad Sci U S A. 2009 Sep 1;106(35):14914-9. Epub 2009 Aug 24.
Destabilizing protein polymorphisms in the genetic background direct phenotypic expression of mutant SOD1 toxicity. Gidalevitz T, Krupinski T, Garcia S, Morimoto RI. PLoS Genet. 2009 Mar;5(3):e1000399. Epub 2009 Mar 6.
Stress-inducible regulation of heat shock factor 1 by the deacetylase SIRT1. Westerheide SD, Anckar J, Stevens SM Jr, Sistonen L, Morimoto RI. Science. 2009 Feb 20;323(5917):1063-6.
Proteotoxic stress and inducible chaperone networks in neurodegenerative disease and aging. Morimoto RI. Genes Dev. 2008 Jun 1;22(11):1427-38. Review.
Brignull, H.R., J.F. Morley, S.M. Garcia, and R.I. Morimoto. Modeling Polyglutamine Pathogenesis in C. elegans. Methods in Enzymology 412: 256-282 (2006).
Westerheide, S., T. Kawahara, K. Orton, and R.I. Morimoto. Triptolide, an Inhibitor of the Human Heat Shock Response that Enhances Stress-Induced Cell Death. J. Biol. Chem. 281: 9616-9622 (2006).
Matsumoto, G., S. Kim, and R.I. Morimoto. Huntingtin and mutant SOD1 form aggregate structures with distinct molecular properties in human cells. J Biol Chem. 281: 4477-4485 (2006).
View all publications by Richard I. Morimoto listed in the National Library of Medicine (PubMed). Past and current IBiS students in blue