Wei-Ling Tsou
Office Address
Department of Pharmacology
540 E. Canfield, 3108 Scott Hall
Detroit, Michigan 48201
Office Phone
Biography
Proteins in the brain are essential for maintaining neuronal homeostasis, supporting communication, stability, and overall nerve cell function. However, in neurodegenerative diseases such as Parkinson’s Disease (PD), these protective mechanisms break down, resulting in progressive neuronal loss, protein aggregation, and motor dysfunction. My research aims to uncover the molecular and cellular pathways underlying neurodegeneration, with the ultimate goal of identifying therapeutic targets to slow or prevent disease progression.
One of the primary areas of my research is polyamine metabolism in PD. Polyamines are essential for cell growth, gene regulation, and oxidative stress balance, but their dysregulation has been linked to α-synuclein aggregation, a key pathological feature of PD. Using Drosophila models and neuronal cultures, we investigate how polyamine pathways influence protein homeostasis, mitochondrial function, and neuronal survival, and whether targeting these pathways can help protect neurons from degeneration.
I actively collaborate with Dr. Peter LeWitt, a leading neurologist specializing in PD, and Dr. Sokol Todi, an expert in protein quality control and neurodegeneration. Working with Dr. LeWitt, we study biomarkers and biochemical pathways associated with PD progression, with a particular focus on L-ornithine-derived polyamine metabolism as a potential disease marker. Our research aims to determine how polyamine dysregulation contributes to α-synuclein aggregation and mitochondrial dysfunction, two critical aspects of PD pathology. Additionally, in collaboration with Dr. Todi, we explore the role of deubiquitinating enzymes (DUBs) in neuronal homeostasis and their impact on protein degradation pathways. Understanding how ubiquitin-dependent processes regulate neurodegeneration may provide new opportunities for therapeutic intervention.
By integrating genetics, molecular biology, and translational research, my lab strives to bridge the gap between fundamental neuroscience and clinical applications. We are committed to mentoring students and researchers, fostering a collaborative and supportive environment that encourages scientific curiosity and innovation. Those interested in neurodegenerative disease research are welcome to join us in our efforts to understand PD and develop new strategies for treatment and prevention.
Current Lab Personnel:
- Bedri Ranxhi, Pharmacology PhD Student
- Zoya R. Bangash, Undergraduate Research Assistant
- Zachary M. Chbihi, Undergraduate Research Assistant
- Nazin N. Islam, Undergraduate Research Assistant
- Sama Fadloun, B.S., Research Assistant
- Carlos Santos, Undergraduate Research Assistant
Training
Post-doctoral fellow
Department of Pharmacology, Wayne State University School of Medicine, Detroit, MI, U.S.A.
Dr. Sokol Todi Labotory, 2011-2013
Research Associate
Department of Pharmacology, Wayne State University School of Medicine, Detroit, MI, U.S.A.
Dr. Sokol Todi Labotory, 2013-2016
Education
Baccalaureate:
Taipei Medical University, Taipei, Taiwan.
B.Sc. in Nutrition and Health Sciences, June 1998.
Graduate:
Taipei Medical University, Taipei, Taiwan.
M.Sc. in Medical Sciences, June 2004.
National Yang Ming University, Taipei, Taiwan.
Exchange student in University of Michigan Medical School, Ann Arbor, MI, U.S.A.
Ph.D. in Neuroscience, June 2011.
Publications
Ranxhi B, Bangash ZR, Chbihi ZM, Qadri Z, Islam NN,Todi SV, LeWitt PA, Tsou W-L. Regulation of polyamine interconversion enzymes affects α-Synuclein levels and toxicity in a Drosophila model of Parkinson’s disease. (Manuscript submitted to Movement Disorders in March. 2025). (Senior author)
Prifti MV, Nuga O, Dulay RO, Patel NC, Kula T, Libohova K, Jackson-Butler A, Tsou WL, Richardson K, Todi SV. Insights into dentatorubral-pallidoluysian atrophy from a new Drosophila model of disease. Neurobiol Dis. (2025) Feb 5:106834. doi: 10.1016/j.nbd.2025.106834.
Ranxhi B, Chbihi ZM, Bangash ZR, Todi SV, LeWitt PA, Tsou W-L. The Role of Akt Pathway in Pathogenesis of α-Synucleinopathy. Front. Mol. Neurosci. (2025) 18:1524044. doi: 10.3389/fnmol.2025.1524044 (Senior author)
Sujkowski A, Ranxhi B, Bangash ZR, Chbihi ZM, Prifti MV, Qadri Z, Alam N, Todi SV, Tsou W-L. Progressive degeneration in a new Drosophila model of Spinocerebellar Ataxia type 7. Sci Rep. (2024) Jun 21;14(1):14332. doi: 10.1038/s41598-024-65172-4. PMID: 38906973 (Senior author)
Blount JR, Patel N, Libohova K, Harris AL, Tsou W-L, Sujkowski AL, Todi SV. Lysine 117 on ataxin-3 modulates toxicity in Drosophila models of Spinocerebellar Ataxia Type 3. J Neurol Sci. (2023) Nov 15;454:120828. doi: 10.1016/j.jns.2023.120828. PMID: 37865002.
Prifti MV, Libohova K, Harris AL, Tsou W-L, Todi SV. Ubiquitin-binding site 1 of pathogenic ataxin-3 regulates its toxicity in Drosophila models of Spinocerebellar Ataxia Type 3. Front Neurosci. (2023) Jan 17;16:1112688. doi: 10.3389/fnins.2022.1112688. eCollection 2022. PMID: 36733922.
Johnson SL, Prifti MV, Sujkowski AL, Libohova K, Blount JR, Hong L, Tsou W-L, Todi SV. Drosophila as a model of unconventional translation in spinocerebellar ataxia type 3. Cells.(2022) Apr 4;11(7):1223. doi: 10.3390/cells11071223.
Johnson SL, Libohova K, Blount JR, Sujkowski AL, Prifti MV, Tsou W-L, Todi SV. Targeting the VCP-binding motif of ataxin-3 improves phenotypes in Drosophila models of Spinocerebellar Ataxia Type 3. Neurobiology of Disease.(2021) Sep 24;160:105516. doi: 10.1016/j.nbd.2021.105516.
Johnson SL, Ranxhi B, Libohova K, Paulson HL, Tsou W-L*, Todi SV*. Ubiquitin-interacting motifs of ataxin-3 regulate its polyglutamine toxicity through Hsc70-4-dependent aggregation. Elife. (2020) Sep 21;9:e60742. doi: 10.7554/eLife.60742. PMID: 32955441 (*Co-senior author)
Pedersen A, Petriv AM, Meyer DN, Soto A, Shields J, Akemann C, Baker BB, Tsou W-L, Zhang Y, Baker TR. Nanoplastics impact the zebrafish (Danio rerio) transcriptome: Associated developmental and neurobehavioral consequences. Environmental Pollution. (2020) Nov;266(Pt 2):115090. doi: 10.1016/j.envpol.2020.115090. Epub 2020 Jul 16. PMID: 32693326 PMCID: PMC7492438
Blount JR, Johnson SL, Libohova K, Todi SV, Tsou W-L. Degron capability of the hydrophobic C-terminus of the polyglutamine disease protein, ataxin-3. Journal of Neuroscience Research. (2020) Oct;98(10):2096-2108. doi: 10.1002/jnr.24684. Epub 2020 Jul 9. (Senior author)
Johnson SL, Blount JR, Libohova K, Ranxhi B, Paulson HL, Tsou W-L*, Todi SV*. Differential toxicity from ataxin-3 isoforms in Drosophila models of Spinocerebellar Ataxia Type 3. Neurobiology of Disease. (2019) Jul 13;132:104535. doi: 10.1016/j.nbd.2019.104535. PMID: 31310802 (*Co-senior author)
Sutton JR, Blount JR, Libohova K, Tsou W-L, Joshi GS, Paulson HL, do Carmo Costa M, Scaglione MK, Todi SV. Interaction of the polyglutamine protein ataxin-3 with Rad23 regulates toxicity in Drosophila models of Spinocerebellar Ataxia Type 3. Human Molecular Genetics. (2017) Feb 1. doi: 10.1093/hmg/ddx039. PMID: 28158474
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) Dec 15;5(12):1770-1775. doi: 10.1242/bio.021667. PMID: 27979829 (First author)
Ristic G, Tsou W-L, Guzi E, Kanack A, Scaglione KM, Todi SV. USP5 is dispensable for mono-ubiquitin maintenance in Drosophila. Journal of Biological Chemistry. (2016) Apr 22;291(17):9161-72. doi: 10.1074/jbc.M115.703504. PMID: 26917723
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) Oct; 82:12-21. doi: 10.1016/j.nbd.2015.05.010. PMID: 26007638 (First author)
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(15):4385-96. doi: 10.1093/hmg/ddv174. PMID: 25954029 (First author)
Blount JR*, Tsou W-L*, 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. Nature Communications, (2014) 5:4638. doi: 10.1038/ncomms5638. PMID: 25144244 (*Co-first author)
Burr AA, Tsou W-L, Ristic G, Todi SV. Using membrane-targeted green fluorescent protein to monitor neurotoxic protein-dependent degeneration of Drosophila Eyes. Journal of Neuroscience Research, (2014) 92(9): 1100-09. PMID: 24798551
Tsou W-L, Burr AA, Ouyang M, Blount JR, Scaglione KM, Todi SV. Ubiquitination regulates the neuroprotective function of the deubiquitinase ataxin-3 in vivo. Journal of Biological Chemistry, (2013) 288(48): 34460-69. PMID: 24106274 (First author)
Tsou W-L, Sheedlo MJ, Morrow ME, Blount JR, McGregor KM, Das C, Todi SV. Systematic analysis of the physiological significance of Deubiquitinating Enzymes. PLoS ONE, (2012) 7(8): e43112. doi:10.1371/journal.pone.0043112. PMID: 22937016 (First author)
Tsou W-L, Soong BW, Paulson HL, Rodríguez-Lebrón E. Splice isoform-specific suppression of the Cav2.1 variant underlying spinocerebellar ataxia type 6. Neurobiology of Disease, (2011) Vol 43(3): 533-42. doi: 10.1016/j.nbd.2011.04.016. PMID: 21550405 (First author)
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