Wei-Ling Tsou
Biography
Dr. Wei-Ling Tsou is dedicated to unraveling the molecular intricacies behind age-related neurodegeneration, focusing on polyglutamine-dependent Spinocerebellar Ataxias (SCAs) and proteinopathies associated with Parkinson’s Disease. I aim to explore the pathogenicity of proteins involved in neuronal aggregation and develop strategies to counteract these harmful mechanisms. By utilizing Drosophila melanogaster and cell culture systems, I focus on the causes of neuronal toxicity, particularly protein quality control and oxidative stress pathways.
My goal is to translate these insights into meaningful therapeutic interventions that can aid in disease management and early prevention. Over the years, I’ve been fortunate to contribute to the field through numerous publications. I have also had the privilege of presenting our findings at both national and international conferences.
Beyond my research, I mentor graduate students and research assistants, guiding them through experimental techniques and troubleshooting, helping them to advance in their careers. Ultimately, I am driven by a passion for discovery and a desire to find real solutions to the challenges posed by neurodegenerative diseases.
Education
Research Associate, Department of Pharmacology, Wayne State University School of Medicine
Post-doctoral fellow, Department of Pharmacology, Wayne State University School of Medicine
Ph.D. in Neuroscience, National Yang-Ming University, Taipei, Taiwan.
M.Sc. in Medical Sciences, Taipei Medical University, Taipei, Taiwan.
B.Sc. in Nutrition and Health Sciences, Taipei Medical University, Taipei, Taiwan.
Research
Parkinson's Disease (PD)--
Proteinopathies: My research targets the molecular mechanisms behind protein aggregation and neuronal toxicity in Parkinson’s Disease, with a special focus on α-synuclein, a protein implicated in PD pathology.
Polyamine Metabolism: A major area of my work investigates the role of polyamine metabolism in PD. My lab explores how manipulating polyamine pathways impacts α-synuclein aggregation and neurotoxicity. We have shown that altering polyamine metabolism can reduce α-synuclein levels and prolong neuron longevity in Drosophila models.
Therapeutic Targets: My studies aim to identify new therapeutic strategies by modulating key pathways like oxidative stress and protein aggregation, which could help slow or stop the progression of PD. This includes testing new compounds that target polyamine metabolism for potential PD therapies.
Spinocerebellar Ataxias (SCAs)--
Spinocerebellar Ataxia Type 3 (SCA3): I developed novel Drosophila models to study SCA3, specifically exploring how different protein domains of ataxin-3 (such as lysine 117, ubiquitin-binding sites, and the VCP-binding domain) influence the toxicity caused by polyglutamine expansion. This research has revealed crucial interactions between ataxin-3 and proteins in the proteasomal degradation system, which contribute to neuronal degeneration.
Spinocerebellar Ataxia Type 6 (SCA6): In addition to SCA3, I created a Drosophila model for SCA6 that expresses both the wild-type and mutant forms of α1aCT. This model has been instrumental in identifying key protein quality control mechanisms, including the roles of chaperone protein DnaJ-1 and Karyopherin α-3 in reducing polyglutamine-induced toxicity. These insights have expanded our understanding of protein misfolding and aggregation in SCA6.
Spinocerebellar Ataxia Type 7 (SCA7): Another key focus of my research is SCA7, where I developed Drosophila models expressing full-length ataxin-7 to study the progressive neurodegeneration characteristic of this disease. These models allow for precise examination of the molecular pathways driving SCA7 neurodegeneration. Our findings contribute to future research aimed at developing novel therapeutics for SCA7 patients and their families.
Publications
1. 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)
2. 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.
3. 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.
4. 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.
5. 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.
6. 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)
7. 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
8. 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)
9. 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)
Office Address
540 E Canfield
Rm. 3108 Scott Hall
Detroit, MI 48201