Sokol V. Todi
Sokol V. Todi, Ph.D.
Departments of Oncology, Neurology, Pharmacology
540 E. Canfield, Room 6105
Detroit, MI 48201
- Ubiquitin-Dependent Pathways
- The role of Deubiquitinating enzymes in cell biology
- Discovery of new therapeutic targets for cancer and neurodegeneration
Our laboratory studies ubiquitin-dependent pathways involved in protein quality control. Post-translational modification of proteins by ubiquitin (Figure 1) regulates almost every cellular process and pathway, from gene expression to protein degradation, from cell division to cell death. The process of ubiquitin removal (deubiquitination), accomplished by a large family of proteases known as deubiquitnating enzymes (DUBs), is a central component of ubiquitin-dependent pathways. Due to their direct involvement in regulating ubiquitin homeostasis and protein fate (Figure 2), DUBs have been linked to many diseases, including several types of cancer and neurological diseases.
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Our newly established laboratory studies the role of DUBs in neurodegeneration, and more recently in breast and prostate malignancies. We are currently conducting several projects, including:
- The role of the DUB JosD1 in cell division and cell migration
- The role of USP-class DUBs in protein quality control in cancer and in neurodegeneration
- Understanding enzymatic properties and discovering interacting partners of DUBs involved in cancer and in neurodegeneration, with the hope of targeting for future therapy.
Ristic G, Tsou WL, Todi SV. An optimal ubiquitin-proteasome pathway in the nervous system: the role of deubiquitinating enzymes. Front Mol Neurosci. 2014;7:72.
Blount JR, Tsou WL, Ristic G, Burr AA, Ouyang M, Galante H, Scaglione KM, Todi SV. Ubiquitin-binding site 2 of ataxin-3 prevents its proteasomal degradation by interacting with Rad23. Nat Commun. 2014;5:4638.
Burr AA, Tsou WL, Ristic G, Todi SV. Using membrane-targeted green fluorescent protein to monitor neurotoxic protein-dependent degeneration of Drosophila eyes. J Neurosci Res. 2014;92:1100-9.
Faggiano S, Menon RP, Kelly GP, McCormick J, Todi SV, Scaglione KM, Paulson HL, Pastore A. Enzymatic production of mono-ubiquitinated proteins for structural studies: The example of the Josephin domain of ataxin-3. FEBS Open Bio. 2013;3:453-8.
Tsou WL, Burr AA, Ouyang M, Blount JR, Scaglione KM, Todi SV. Ubiquitination regulates the neuroprotective function of the deubiquitinase ataxin-3 in vivo. J Biol Chem. 2013;288:34460-9.
Scaglione KM, Basrur V, Ashraf NS, Konen JR, Elenitoba-Johnson KS, Todi SV, Paulson HL. The ubiquitin-conjugating enzyme (E2) Ube2w ubiquitinates the N terminus of substrates. J Biol Chem. 2013;288:18784-8.
Seki T, Gong L, Williams AJ, Sakai N, Todi SV, Paulson HL. JosD1, a membrane-targeted deubiquitinating enzyme, is activated by ubiquitination and regulates membrane dynamics, cell motility, and endocytosis. J Biol Chem. 2013 ;288:17145-55.
Education and Training:
PhD (2005): University of Iowa, Iowa City, Iowa
Post-Doctoral Training (2005-2007): University of Iowa, Iowa City, Iowa
Post-Doctoral Training (2007-2010): University of Michigan, Ann Arbor, Michigan