Richard Morimoto Professor

Research Summary: 

We are interested in cell stress regulatory pathways and protein homeostasis (proteostasis) that ensures the stability of the proteome in health and when challenged by cell stress and the expression of metastable, misfolded, and aggregated proteins.   Using C. elegans and human iPS cells, we employ genetic, molecular, small molecule, proteomic and genomic methods and systems level analyses to identify changes during aging and age-associated diseases including metabolic diseases, cancer, and neurodegeneration.

Selected Publications:

Protein Homeostasis of a Metastable Subproteome Associated with Alzheimer’s Disease. Kundra, R., P. Ciryam, R. I. Morimoto, C. M. Dobson, and M. Vendruscolo. Proc. Natl. Acad. Sci. USA., DOI: 10.1073/pnas.1618417114 (2017).

A Transcriptional Signature of Alzheimer’s Disease is Associated with a Metastable Subproteome at Risk for Aggregation. Ciryam, P., R. Kundra, R. Freer, R. I. Morimoto, C. M. Dobson, and M. Vendruscolo. Proc. Natl. Acad. Sci. U.S.A., DOI: 10.1073 (2016). 

E2F Co-regulates an Essential HSF Developmental Program Distinct from the Heat Shock Response. Li, J., L. Chauve, G. Phelps, R. Brielmann, and R.I. Morimoto. Genes and Development 30: 2062-2075 PMID 27688402. 2016 Sep 15, Epub 2016 Sep 29.

Repression of the Heat Shock Response is a Programmed Event at the Onset of Reproduction. Labbadia, J. and R.I. Morimoto. Molecular Cell Vol. 59, Issue 4: 639-650, DOI 10.1016/j. molcel.2015.06.027 PMID: 266212459. 2015, August 20. Epub 2015, July 23.

Proteotoxic Stress and Ageing Triggers the Loss of Redox Homeostasis Across Cellular Compartments. Kirstein, J., D. Morito, T. Kakihana, M. Sugihara, A. Minnen, M.S. Hipp, C. Nussbaum-Krammer, F.U. Hartl, K. Nagata, and R.I. Morimoto.  EMBO Journal 34: 2334-2349, PMID:26228940 (2015).

Crucial Hsp70 Co-chaperone Complex Unlocks Metazoan Protein Disaggregation.  Nillegoda, N.B., J. Kirstein, A. Szlachcic, M. Berynskyy, A. Stank, F. Stenge⁴, K. Arnsburg, X. Gao, R. Aebersold, D.L. Guilbride, R.C. Wade, R.I. Morimoto, M.P. Mayer, and B. Bukau.   Nature 524: 247-251, DOI: 10.1038/nature14884, PMID:26245380 (2015).

Spreading of a Prion Domain from Cell-to-Cell by Vesicular Transport in Caenorhabditis elegans. Nussbaum-Krammer CI, Park K-W, Li L, Melki R, and Morimoto RI. PLoS Genetics. 2013 March 28;9(3):e1003351.

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.

Neuronal reprograming of protein homeostasis by calcium-dependent regulation of the heat shock response. Silva MC, Amaral MD, Morimoto RI. PLoS Genet. 2013 Aug;9(8):e1003711.

Widespread aggregation and neurodegenerative diseases are associated with supersaturated proteins. Ciryam P, Tartaglia GG, Morimoto RI, Dobson CM, Vendruscolo M. Cell Rep. 2013 Nov 14;5(3):781-90.

Selected Honors:

Fyodor Lynen Lecturer – German Society of Biochemistry

Commandeur, Ordre des Palmes Académiques, France

Elected Fellow – American Academy of Arts and Sciences

National Institutes of Health MERIT Award

Doctor of Philosophy, Honoris Causa – Abo Akademi University, Turku, Finland