Sokol  Todi, PhD

Sokol Todi, PhD

stodi@med.wayne.edu

313 577 1173

Sokol Todi, PhD

Narrative Bio

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). Dr. Todi’s laboratory investigates mechanisms of neurodegeneration and neuroprotection in age-dependent neurodegenerative diseases caused by misfolded proteins, with particular focus on polyglutamine disease proteins.

Research Summary:

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.

Other 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. 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.

 

 

Office Address

 Scott Hall, Suite 3108

Awards & Honors

 2017 – 2018 Career Development Chair, WSU.
10/2015 Award for Excellence in Research, WSU School of Medicine.
10/2014 Award for Excellence in Instruction and Teaching, WSU School of Medicine.
12/2012 Young Investigator in Spinocerebellar Ataxias, National Ataxia Foundation.
12/2011 Young Investigator in Spinocerebellar Ataxias, National Ataxia Foundation.
09/2009 K99/R00 Career Advancement Award, NINDS.
01/2008 Post-Doctoral Travel Award, American Society for Biochemistry and Molecular Biology Annual Meeting.
01/2006 Research Fellowship, National Ataxia Foundation.
01/2004 Pre-Doctoral Fellowship, American Heart Association.
12/2003 Graduate Incentive Fellowship, University of Iowa.
11/2003 Graduate Student Travel Fellowship, Society for Neuroscience Meeting.

Other Information

 

Undergraduate

University of Nebraska-Lincoln, B.Sc. (Biological Sciences) 1995. High Distinction Graduate

Graduate

University of Iowa, Iowa City, IA, PhD (Neuroscience) 2005

Position Title

Associate Professor of Pharmacology and Neurology

Fellowships

Post-Doctoral Fellow, University of Iowa College of Medicine, 2005-2007. Ubiquitin-dependent pathways in neurodegenerative diseases.

Post-Doctoral Fellow, University of Michigan Medical School, 2007-2010. Ubiquitin-dependent pathways in neurodegenerative diseases.

Prior Appointments

Research Assistant Professor, Neurology, University of Michigan, 2010

Interests

Age-related neurodegenerative diseases, molecular mechanisms of neurodegeneration and neuroprotection, ubiquitin-dependent pathways in cell function, deubiquitinating enzymes, ataxias, polyglutamine diseases, multiple sclerosis.

Publications

(SELECTED):

1. 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.
2. 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.
3. Ristic G*#, Sutton JR*#, Libohova K, Todi SV (2018). 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. doi: 10.1016/j.nbd.2018.04.013.
4. Murray AS, Varela FA#, Hyland TE, Schoenbeck AJ, White JM, Tanabe LM, Todi SV, List K (2017). 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. doi: 10.1074/jbc.M117.775999. (SVT:
5. Das B, Rahagopalan S, Joshi GS#, Kandegedara A, Xu L, Lou D, Andersen JK, Todi SV, Dutta A (2017). A novel iron (II) preferring dopamine agonist chelator D-607 significantly suppresses α-Syn- and MPTP-induced toxicities in vivo. Neuropharmacology. doi: 10.1016/j.neuropharm.2017.05.019. (SVT: Conceptualized part of
6. Sutton JR#, Blount JR#, Libohova K, Tsou W-L#, Joshi GS#, Paulson HL, Costa MDo, Scaglione KM, Todi SV (2017). Interaction of the polyglutamine disease protein ataxin-3 with Rad23 controls its pathogenicity in Drosophila models of Spinocerebellar Ataxia Type 3. Human Molecular Genetics. doi: 10.1093/hmg/ddx039.
7. Tsou W-L#, Qiblawi SH, Hosking RR, Gomez CM, Todi SV (2016). Polyglutamine length-dependent toxicity from α1ACT in Drosophila models of Spinocerebellar Ataxia Type 6. Biology Open. doi:10.1242/bio.021667.
8. Yedlapudi D, Joshi GS#, Luo D, Todi SV, Dutta AK (2016). 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. doi:
9. 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 (2016). Unbiased screen identifies aripiprazole as a modulator of abundance of the polyglutamine disease protein, ataxin-3. Brain. doi: 10.1093/brain/aww228.
10. Ristic G#, Guzi E#, Tsou W-L#, Kanack A, Scaglione KM, Todi SV (2016). USP5 is dispensable for monoubiquitin maintenance in Drosophila. Journal of Biological Chemistry. doi: 10.1074/jbc.M115.703504.
11. Tsou W-L#, Ouyang M#, Hosking RR, Sutton JR#, Blount JR, Burr AA#, Todi SV (2015). The deubiquitinase ataxin-3 requires Rad23 and DnaJ-1 for its neuroprotective role in Drosophila. Neurobiology of Disease. doi: 10.1016/j.nbd.2015.05.010.
12. Tsou W-L#, Hosking RR, Burr AA#, Sutton JR#, Ouyang M#, Du X, Gomez CM, Todi SV (2015). DnaJ-1 and karyopherin α3 suppress degeneration in a new Drosophila model of Spinocerebellar Ataxia Type 6. Human Molecular Genetics, 24(15):4385-96. doi: 10.1093/hmg/ddv174.
13. Blount JR*, Tsou W-L#*, Ristic G#, Burr AA#, Ouyang M#, Galante H, Scaglione KM, Todi SV (2014). Ubiquitin-binding site 2 of ataxin-3 prevents its proteasomal degradation by interacting with Rad23. Nature Communications, 5:4638. doi: 10.1038/ncomms5638.
14. Burr AA#, Tsou W-L#, Ristic G#, Todi SV (2014). Using membrane-targeted green fluorescent protein to monitor neurotoxic protein-dependent degeneration of Drosophila eyes. Journal of Neuroscience Research, 92(9): 1100-09.
15. Tsou W-L#, Burr AA#, Ouyang M#, Blount JR, Scaglione KM, Todi SV (2013). Ubiquitination regulates the neuroprotective function of the deubiquitinase ataxin-3 in vivo. Journal of Biological Chemistry, 288(48): 34460-69.
16. Seki T, Gong L, Williams AJ, Sakai N, Todi SV, Paulson HL (2013). JosD1, a membrane-targeted deubiquitinating enzyme, is activated by ubiquitination and regulates membrane dynamics, cell motility and endocytosis. Journal of Biological Chemistry. (SVT:
17. Tsou W-L#, Sheedlo MJ*, Morrow ME*, Blount JR, McGregor KM#, Das C, Todi SV (2012). Systematic analysis of the physiological significance of Deubiquitinating Enzymes. PLoS ONE, 7(8): e43112. doi:10.1371/journal.pone.0043112.
18. Blount JR, Burr AA#, Denuc A, Marfany G, Todi SV (2012). Ubiquitin-Specific Protease 25 functions in Endoplasmic Reticulum-Associated Degradation. PLoS ONE, 7(5): e36542. doi:10.1371/journal.pone.0036542.
19. Scaglione KM, Zavodszky E, Todi SV, Patury S, Xu P, Rodriguez-Lebron E, Fischer S, Konen J, Djarmati A, Peng J, Gestwicki J, Paulson HL (2011). Ube2w and ataxin-3 coordinately regulate the ubiquitin ligase CHIP. Molecular Cell, 43: 599-612. (SVT:
20. Todi SV, Scaglione KM, Blount JR#, Basrur V, Conlon PK, Pastore A, Elenitoba-Johnson K, Paulson HL (2010). Activity and cellular functions of the deubiquitinating enzyme and polyglutamine disease protein ataxin-3 are regulated by ubiquitination at lysine 117. Journal of Biological Chemistry, 285(50): 39303-13.
21. Nicastro G*, Todi SV*, Karaca E, Bonvin AMJJ, Paulson HL, Pastore A (2010). Understanding the role of the Josephin domain in the polyUb binding and cleavage properties of ataxin-3. PLoS ONE, 5(8): e12430. doi:10.1371/journal.pone.0012430.
22. Todi SV, Winborn BJ#, Scaglione KM, Blount JR#, Travis SM, Paulson HL (2009). Ubiquitination directly enhances activity of the deubiquitinating enzyme ataxin-3. The EMBO Journal, 28(4): 372-82.

 

 

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