Written by Victoria Martinez
Faces of Ataxia Research highlights scientists whose work is supported by grants from NAF. Each story shows how our donors are fueling discoveries that bring us closer to effective treatments and a cure for Ataxia.
Meet the Researcher
Project title:
- Pioneer SCA Translational Award (2019): “Mechanisms of aggregation and toxicity in SCA3”
- Pioneer SCA Translational Award (2021): “Targeting Hsc70-4 to
mitigate SCA3/MJD”
Education:
BSc, University of Nebraska-Lincoln
PhD, University of Iowa, Iowa City, IA
Post-Doctoral Fellow, University of Iowa College of Medicine
Post-Doctoral Fellow, University of Michigan Medical School
Current Position:
- Professor and Chair at Wayne State University, School of Medicine, Department of Pharmacology
Path to Ataxia Research
Dr. Todi’s journey into ataxia research began at the University of Nebraska,
Lincoln, where he arrived as an international student from Albania. There he developed a strong interest in physiology and neuroscience throughout his undergraduate studies.
Dr. Todi then completed a PhD in neuroscience at the University of Iowa, studying theauditory system of fruit flies. He used electrophysiology, microscopy, and developmental biology techniques to understand auditory transduction. Moving forward into his post-doctoral fellowships, Dr. Todi chose to focus on age-dependent diseases of the nervous system, particularly those involving polyglutamine expansions.
For his postdoctoral fellowship at the University of Iowa, Dr. Todi joined Dr. Hank Paulson’s lab to study Spinocerebellar Ataxia Type 3 (SCA3), caused by a polyglutamine expansion in the ataxin-3 protein. There, he applied biochemical techniques and enzymology principles to investigate the mechanisms underlying age-dependent neurodegeneration. Neurodegeneration is characterized by the gradual, irreversible malfunction and death of neurons, in this case, as a person ages. Dr. Todi
decided to investigate what cellular processes trigger the gradual loss of neuronal function over time. His exposure to ataxia research deepened through attendance at neuroscience conferences, which ultimately inspired him to focus on ataxia when he started his own lab.
Focus of Current Research
Dr. Todi’s laboratory investigates shared mechanisms of action among different ataxia-causing proteins and how they damage nerve cells. Dr. Todi works with both fruit flies and mammalian cell lines in the lab, ensuring they express similar genetic profiles to ataxia in humans. The Todi lab uses a mix of tools to simultaneously map active genes and proteins, visually assess cells through microscopy, and evaluate cell protective mechanisms, while isolating differences across compartments and between male and female subjects. The lab also studies how long the flies live and how well they can move, and even tests whether exercise can help. The goal is to connect what happens at the molecular level to the symptoms patients experience, so future treatments can target the problem more effectively.
Why Ataxia Research Matters
Dr. Todi’s focus in research stems from being interested in age-dependent diseases that impact the nervous system. Pursuing this interest led to him studying SCA3 early in his career. Ataxia research took on greater personal significance after he attended conferences and met people living with the condition. There he recognized the impact incurable diseases have on patients, families, and future generations. This human connection, combined with his interest in molecular biology and animal physiology, deepened his commitment to studying the inherited forms of ataxia.
Research Impact on the Ataxia Community
The Todi Lab aims to generate baseline data that can inform more complex projects. Over time, this will support the development of ataxia treatments. The Todi lab uses fly models and mammalian cell lines to map protein interactions and visualize the effects of cytotoxicity on neurons and glial cells. Through this work, they hope to identify what helps regulate protein toxicity. These insights could ultimately contribute to reducing symptoms or slowing disease progression.
Advancements through NAF Funding
Multiple grants over the years from NAF allowed Dr. Todi to pursue hypotheses that would not have been feasible to support otherwise. They would not have been possible without NAF funding due to their exploratory nature, and the lack of supporting literature and preliminary data in the field at the time. As a result, Dr. Todi was able to focus on identifying protein interactions for ataxin-3 and determining how these interactions influence the degree of cytotoxicity. The 2021 Pioneer SCA translational award enabled Dr. Todi to generate foundational data that not only advanced his understanding of ataxin-3 biology but also helped launch his career in ataxia research. This has permitted him to continue to research ataxia. This has led to his current research in fruit fly and mammalian cell models to examine protein–protein interactions.
Bridging Gaps in Knowledge
The Todi Lab aims to bridge the gap between promising results in animal models and successful treatments for patients with ataxia. Dr. Todi’s research focuses on reducing cell damage or boosting the cell’s natural protective systems, with the goal of generating strong preliminary data to guide the field. By identifying shared mechanistic pathways across different ataxia types, or simply negative data, the lab lays essential groundwork for future studies, drug development, and a deeper understanding of the biochemical changes driving ataxia and neurodegeneration.
Career Growth Through NAF Support
Receiving a NAF grant was instrumental in advancing Dr. Todi’s career. It provided crucial funding and data that supported his promotion and tenure at Wayne State University. The work funded by NAF laid the groundwork for securing larger grants from government organizations such as the NIH.
Long-Term Goals
Dr. Todi’s overarching goal is to mentor the next generation of scientists. Recognizing the rapid advances in technology and AI, he feels it is essential to empower emerging researchers. This includes supporting a wide diversity of students from various fields approaching neuroscience from unconventional perspectives. His commitment to mentorship is a key influence of his work. Additionally, Dr. Todi hopes his work will provide clear therapeutic insights, particularly for ataxia types with well-defined targets. At a minimum, he aims to contribute preliminary genetic and biochemical data that can guide future treatment development.
Hobbies Outside the Lab
Outside of the lab, Dr. Todi enjoys Italian opera, a passion fueled by his love of music and a way to keep up with the language. His husband jokes that Dr. Todi isn’t allowed to talk about opera for more than five minutes with a stranger, or else he’ll go on forever. Dr. Todi frequently attends performances in Detroit and New York City. He appreciates appreciating the nuances by seeing successive shows and isolating and appreciating the subtle variations of live performance and orchestras.
