Written by Taylor Stolberg
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:
- Graduate Research Fellowship (2024): “Elucidating cholesterol impairments in spinocerebellar ataxia type 3: a mechanism underlying oligodendrocyte maturation deficits ”
Education:
- B.S., Neuroscience, Duke University
Current Position:
- Neuroscience PhD Candidate at the University of Michigan, under the supervision of Hayley McLoughlin, PhD
Path to Ataxia Research
Alexa’s interest in ataxia started in undergrad. At Duke, Alexa joined a research lab studying pathology in Huntington’s Disease (HD), a polyglutamine disease. Polyglutamine diseases are genetic conditions caused by a mutation in which the amino acid glutamine is repeated more times in a protein than it should be. Polyglutamine diseases include HD and several types of ataxias, including Spinocerebellar ataxia types 1, 2, and 3.
Excited by the mission of the work, Alexa wanted to continue neurodegeneration research, specifically in polyglutamine diseases. When Alexa started graduate school at the University of Michigan, she joined Dr. Hayley McLoughlin’s lab. She was intrigued by Dr. McLoughlin’s work on Spinocerebellar ataxia type 3 (SCA3) and appreciated the large ataxia research community at the University of Michigan.
Focus of Current Research
Currently, Alexa studies the role of oligodendrocytes in SCA3 disease progression. Oligodendrocytes are a type of brain cell that produce a substance known as myelin. Myelin is a fatty (‘lipid’) coating that covers neurons. The function of myelin is to insulate neurons, thereby speeding up neuron electric signaling.
Alexa is investigating how oligodendrocytes become dysfunctional in SCA3. Using genetic mouse models, Dr. McLoughlin’s lab found that myelin-producing oligodendrocytes are reduced in the SCA3 brain. Alexa’s recent studies, funded by NAF, investigated whether lipids (fats) are changed in SCA3 mice. The myelin made by oligodendrocytes is largely composed of lipids. Knowing how lipids are changed in disease could help us better understand the pathology of oligodendrocytes in SCA3.
Why Ataxia Research Matters
Witnessing family members suffer from neurological illnesses, Alexa wanted to develop treatments for similar diseases. This initial personal connection led her to study ataxia in Dr. McLoughlin’s lab.
Additionally, Alexa is excited to study the mechanisms for rare diseases such as ataxia. She emphasized that many basic questions about how ataxia starts and progresses remain unanswered. Learning about these struggles in rare disease patients, Alexa hopes to remain in the ataxia field.
Research Impact on the Ataxia Community
Alexa’s research on oligodendrocyte and lipid changes can have both mechanistic and clinical benefits. To identify treatments for a disease, we need knowledge on how the disease develops at a molecular and cellular level. This includes researching the types of cells altered in diseases.
Alexa’s work in genetic mouse models demonstrates oligodendrocytes are dysfunctional in SCA3. Damage to oligodendrocytes suggests these brain cells are vulnerable to the repeat mutation in SCA3. Understanding oligodendrocyte vulnerability allows researchers such as Alexa to assess whether these cells could be potential therapeutic targets. Currently, there are no FDA-approved cures for SCA3. Investigating how oligodendrocytes and lipids are altered in disease can lead to studies on how to reduce toxicity in this cell type.
Advancements through NAF Funding
Academically, Alexa learned a lot from this work. Firstly, this NAF-funded project opened up a collaboration opportunity with Dr. Stephanie Cologna at the University of Illinois at Chicago. The McLoughlin and Cologna labs ran an unbiased, large-scale study characterizing lipids in both human and mouse SCA3 brain samples, a technique known as lipidomics.
This study allowed Alexa to evaluate which brain lipids were changed in SCA3 disease. For instance, Alexa learned that one type of lipid, cholesterol, was reduced in SCA3 human and mouse samples compared to controls. The results were published in the journal Neurobiology of Disease earlier this year (you can access the article here). Alexa reported that to her knowledge, this was the first unbiased investigation of brain lipids in SCA3.
Bridging Gaps in Knowledge
Prior to her paper, brain lipids had not been extensively investigated in SCA3. Alexa’s work reveals which lipids in the brain are changed, and compares lipid changes across genetic mouse models and patients with SCA3.
As lipids are a major component of brain tissue, this knowledge gives researchers a new understanding about the pathology of SCA3. Understanding lipid changes allows researchers to investigate how these alterations contribute to patient symptoms across the course of disease.
Career Growth Through NAF Support
Receiving a NAF grant has allowed Alexa to continue studying ataxia long-term. Namely, NAF’s investment in Alexa’s research paved the way for support from the National Institute of Neurological Disorders and Stroke through the NRSA F31, a training grant for predoctoral researchers. This grant will fund the remainder of Alexa’s graduate studies, including her ongoing oligodendrocyte and lipid research. The aforementioned publication describing how lipids are altered in SCA3 brains was also a major outcome of this funding.
Alexa is very grateful for the support from the NAF community, and stated during the interview she wants to remain in the ataxia field. After her PhD, she hopes to enter a career in academia. Academic careers involve conducting research and teaching at a university. People in academia may discover new treatment targets, mechanisms of disease, and publish papers to inform others of their work. To enter academia, having a history of funding is important for young researchers. The NAF grant is a first stepping stone for Alexa to become a researcher of ataxia.
Long-Term Goals
Alexa hopes her research can provide new answers to patients on SCA3 pathology. As SCA3 currently has no cure, Alexa hopes her work may give patients more information on the biology of SCA3 and potential therapeutics being researched.
Hobbies Outside the Lab
When away from the lab, Alexa enjoys Pilates, baking, and playing board games with friends.
