Tomohiro Nakamura, PhD
Institute Investigator
Department of Molecular and Cellular Biology
Research Focus
Our group investigates redox biology with a particular emphasis on S-nitrosylation, a nitric oxide (NO)-mediated posttranslational modification in which an NO group reacts with a critical cysteine thiol residue to regulate protein function and activity — analogous to the role of phosphorylation. Excessive NO generation in the nervous system is thought to represent a fundamental pathological mechanism underlying several neurodegenerative disorders, including Alzheimer's disease, frontotemporal dementia, Lewy body dementia, and Parkinson's disease. Our research aims to elucidate the molecular mechanisms by which aberrant protein S-nitrosylation drives mitochondrial dysfunction, protein misfolding, synaptic impairment, and neuronal cell death in the context of neurodegeneration.
Select Publications
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nakamura, tomohiro; yates, john r.; lipton, stuart a.; rissman, robert a.; masliah, eliezer; spencer, brian; scott, henry r.; deal, amanda k.; gibbs, daniel; lopez, kevin; zhang, xu; liao, lujian; oh, chang-ki Noncanonical transnitrosylation network contributes to synapse loss in Alzheimer’s disease. Science 2021, 371.
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nakamura, tomohiro; lipton, stuart a.; tannenbaum, steven r.; zhang, xu; oh, chang-ki Protein Transnitrosylation Signaling Networks Contribute to Inflammaging and Neurodegenerative Disorders. Antioxidants & Redox Signaling 2021, 35, 531-550.
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yates, john r.; nakamura, tomohiro; lipton, stuart a.; yeo, gene w.; martinez, fernando j.; ghatak, swagata; deal, amanda k.; scott, henry r.; cieplak, piotr; han, xuemei; zhang, xu; oh, chang-ki; pirie, elaine S-Nitrosylated TDP-43 triggers aggregation, cell-to-cell spread, and neurotoxicity in hiPSCs and in vivo models of ALS/FTD. Proceedings of the National Academy of Sciences of the United States of America 2021, 118.
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Lipton, Stuart A.; Nakamura, Tomohiro; Cho, Dong-Hyung; Fang, Jianguo; Cieplak, Piotr; Godzik, Adam; Gu, Zezong S-Nitrosylation of Drp1 Mediates ß-Amyloid-Related Mitochondrial Fission and Neuronal Injury. Science 2009, 324, 102-105.
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Oh, Chang- K.; Dolatabadi, Nima; Cieplak, Piotr; Diaz-Meco, Maria T.; Moscat, Jorge; Nolan, John P.; Nakamura, Tomohiro; Lipton, Stu A. S-Nitrosylation of p62 Inhibits Autophagic Flux to Promote a-Synuclein Secretion and Spread in Parkinson's Disease and Lewy Body Dementia. 2022, 42, 3011-3024.