Sokol V. Todi

Sokol V. Todi, Ph.D.
Associate Professor Pharmacology & Neurology
Associate Dean Post-Doctoral Affairs

Laboratory & Office, School of Medicine
540 E. Canfield, Scott Hall, Room 3108
Detroit, Michigan 48201

Office, The Graduate College
5057 Woodward Ave, Room 6307.5
Detroit, Michigan, 48202

Research Interests:

  • Ubiquitin-Dependent Pathways
  • The role of Deubiquitinating enzymes in cell biology
  • Discovery of new therapeutic targets for cancer and neurodegeneration

Research Description:

Dr. Sokol Todi is an Associate Professor in the Departments of Pharmacology and Neurology at Wayne State University School of Medicine. Dr. Todi opened the doors of his laboratory at Wayne State in December 2010 and was awarded Tenure in August 2015. During his time at Wayne State, Dr. Todi has been funded through R00 and R01 mechanisms from the NIH, as well as funds from non-governmental organizations, such as the National Ataxia Foundation, which recognized him two years in a row as a Young Investigator in Spinocerebellar Ataxias. Dr. Todi's work has also been recognized internally at Wayne (e.g. the Career Development Chair Award in 2017).

Dr. Todi's research focuses on two areas. One is the understanding of mechanisms that lead to degeneration in the most common, dominantly inherited ataxia in the world, Spinocerebellar Ataxia Type 3 (SCA3). By using a combination of Drosophila melanogaster genetics, in vitro biochemistry and mammalian cell biology, the Todi laboratory has found new clues into the life cycle of the causative protein in SCA3, ataxin-3: how it acts as an enzyme, its functions, the manner in which it is disposed off in the cell, and what regulates its toxicity in SCA3. Current studies are aimed at understanding how partners of ataxin-3 control its toxicity and how these interactions can be prevented for the purposes of therapy. The other branch of research in the Todi lab focuses on general mechanisms of ubiquitin biology. Ubiquitin (Ub) is a small protein whose chemical conjugation to other proteins regulates their function and fate; Ub-depndent processes have been linked to various diseases, including different types of cancer and age-related neurodegenerative diseases. The Todi lab has made use of fruit fly genetics and in vitro biochemistry to understand how this vital protein is regulated and recycled in the cell.

Selected Publications:

Blount JR, Libohova K, Marsh GB, Sutton JR, Todi SV (2018). Expression and Regulation of Deubiquitinase-Resistant, Unanchored Ubiquitin Chains in Drosophila. Accepted for publication. Scientific Reports.

Nath SR, Yu Z, Gipson TA, Marsh GB, Yoshidome E, Robins DM, Todi SV, Housman DE, Lieberman AP (2018). Age-dependent proteasome dysfunction underlies quality control defects in AR113Q muscle. Accepted for publication. Journal of Clinical Investigation. 

Ristic G*, Sutton JR*, Libohova K, Todi SV. Toxicity and aggregation of the polyglutamine disease protein, ataxin-3 is regulated by its binding to VCP/p97 in Drosophila melanogaster. In press. Neurobiology of Disease 2018;116:78-92.

Murray AS, Varela FA, Hyland TE, Schoenbeck AJ, White JM, Tanabe LM, Todi SV, List K. A novel mechanism regulating type IOI transmembrane serine protease trafficking: Phosphorylation of TMPRSS13 in HAI-1/HAI-2 mediated cell surface localization. Journal of Biological Chemistry 2017;292:14867-84.

Das B, Rahagopalan S, Joshi GS, Kandegedara A, Xu L, Lou D, Andersen JK, Todi SV, Dutta A. A novel iron (II) preferring dopamine agonist chelator D-607 significantly suppresses α-Syn- and MPTP-induced toxicities in vivo. Neuropharmacology 2017;123:88-99.

Sutton JR, Blount JR, Libohova K, Tsou W-L, Joshi GS, Paulson HL, Costa MDo, Scaglione KM, Todi SV. Interaction of the polyglutamine disease protein ataxin-3 with Rad23 controls its pathogenicity in Drosophila models of Spinocerebellar Ataxia Type 3. Human Molecular Genetics 2017;26:1419-31.

Tsou W-L, Qiblawi SH, Hosking RR, Gomez CM, Todi SV. Polyglutamine length-dependent toxicity from α1ACT in Drosophila models of Spinocerebellar Ataxia Type 6. Biology Open 2016;5:1770-5.

Yedlapudi D, Joshi GS, Luo D, Todi SV, Dutta AK. Inhibition of alpha-synuclein aggregation by multifunctional dopamine agonists assessed by a novel in vitro assay and an in vivo Drosophila synucleinopathy model. Scientific Reports 2016;6:38510.

Costa Mdo, Ashraf NS, Fischer S, Yang Y, Schappa E, Joshi GS, McQuade T, Dharia RM, Duschavsky M, Ouyang M, Cook D, Sun D, Larsen MJ, Gestwicki JE, Todi SV, Ivanova MI, Paulson HL. Unbiased screen identifies aripiprazole as a modulator of abundance of the polyglutamine disease protein, ataxin-3. Brain  2016;139:2891-908.

Ristic G, Guzi E, Tsou W-L, Kanack A, Scaglione KM, Todi SV. USP5 is dispensable for monoubiquitin maintenance in Drosophila. Journal of Biological Chemistry. 2016;291:9161-72.

Tsou W-L, Ouyang M, Hosking RR, Sutton JR, Blount JR, Burr AA, Todi SV. The deubiquitinase ataxin-3 requires Rad23 and DnaJ-1 for its neuroprotective role in Drosophila. Neurobiology of Disease. 2015;82:12-21.

Tsou W-L, Hosking RR, Burr AA, Sutton JR, Ouyang M, Du X, Gomez CM, Todi SV.DnaJ-1 and karyopherin α3 suppress degeneration in a new Drosophila model of Spinocerebellar Ataxia Type 6. Human Molecular Genetics 2015; 24:4385-96.

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