Richard I. Morimoto Cell stress responses, molecular chaperones, protein conformational disease

Research Interests

Proteins can adopt a nearly infinite array of conformations that affect function and form or result in dysfunction and toxicity.  We are interested in the biological rules that guide protein conformation in cellular health and fail in human degenerative diseases including Alzheimer’s disease, Parkinson’s disease, ALS, Huntington’s disease, cancer, metabolic diseases and muscle wasting.  Nearly all of these diseases are associated with protein misfolding, aggregation and the formation of amyloids. Our laboratory studies the protein quality control mechanisms regulated by the proteostasis network that regulates chaperone-dependent protein folding, transport and degradation by the ubiquitin-proteasome system and the autophagy lysosome pathway.  We employ genetic, cell biological, biophysical and imaging approaches with C. elegansand patient-derived induced neurons to identify cell protective mechanisms against proteome failure and small molecule approaches to enhance cell stress protective responses to prevent failure in aging.  Our current efforts are to identify the earliest events that predict proteostasis failure in neurons and other tissues in aging, and to develop genetic and therapeutic strategies to slow or reverse this decline.

Selected Publications

Kinetic analysis reveals that independent nucleation events determine the progression of polyglutamine aggregation in C. elegans. Sinnige T, Meisl G, Michaels TCT, Vendruscolo M, Knowles TPJ, and Morimoto RI. PNAS. 2021 March 16;118(11):e2021888118.

Embryo integrity regulates maternal proteostasis and stress resilience. Sala AJ, Bott LC, Brielmann RM, and Morimoto RI. Genes & Development. 2020 May 1;34(9-10):678-687. 

Mitochondrial Stress Restores the Heat Shock Response and Prevents Proteostasis Collapse during Aging. Labbadia J, Brielmann RM, Neto MF, Lin Y-F, Haynes CM, and Morimoto RI. Cell Reports. 2017 November 7;21(6):1481-1494.

Repression of the Heat Shock Response Is a Programmed Event at the Onset of Reproduction. Labbadia J and Morimoto RI. Molecular Cell. 2015 August 20;59(4):639-650.

Widespread Proteome Remodeling and Aggregation in Aging C. elegansWalther DM, Kasturi P, Zheng M, Pinkert S, Vecchi G, Ciryam P, Morimoto RI, Dobson CM, Vendruscolo M, Mann M, and Hartl FU. Cell. 2015 May 7;161(4):919-932.

A Chaperome Subnetwork Safeguards Proteostasis in Aging and Neurodegenerative Disease. Brehme M, Voisine C, Rolland T, Wachi S, Soper JH, Zhu Y, Orton K, Villella A, Garza D, Vidal M, Ge H, and Morimoto RI. Cell Reports. 2014 November 6;9(3):1135-1150.

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. 

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