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

Research Interests

Human lifespan has doubled over the past century, and with this has come the dramatic rise in degenerative diseases including cancer, metabolic and muscle wasting diseases, dementia and Alzheimer’s disease. Our studies on the biology of aging, using C. elegans for discovery science and direct differentiated patient-derived neurons for translation, examines the role of cell stress responses that regulate cell-protective mechanisms and protein quality control, and inter-tissue communication that ensures organismal survival and stress resilience. We employ genetic, molecular and live-cell imaging approaches to identify pathways that are essential for molecular protection against the appearance and accumulation of protein aggregates. These studies ask why proteins associated with Alzheimer’s disease, Huntington’s disease and ALS form toxic aggregating species that interfere with cellular function, how aging leads to a functional decline in the proteostasis machinery for protein folding and degradation which uncovers genetic and small molecule approaches to reset and restore cellular and organismal health.

Selected Publications

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.