Spotlight: The CMRR Ataxia Imaging Team

Location: University of Minnesota, MN, USA

Year Research Group Founded:  2008

What models and techniques do you use?

A photo of the CMRR Ataxia Imaging Team
A photo of the CMRR Ataxia Imaging Team in 2019. Front row, left to right – Diane Hutter, Christophe Lenglet (PI), Gulin Oz (PI), Katie Gundry, Jayashree Chandrasekaran Back row, left to right: Brian Hanna, James Joers, Pramod Pisharady, Kathryn France, Pierre-Gilles Henry (PI), Dinesh Deelchand, Young Woo Park, Isaac Adanyeguh (insert)

Research Group Focus

What shared research questions is your group investigating?

We use high field, multi-nuclear magnetic resonance imaging (MRI) and spectroscopy (MRS) to explore how diseases impact the central nervous system. These changes can be structural, functional, biochemical and metabolic alterations. For example, we apply advanced MRI and MRS methods in neurodegenerative diseases and diabetes.

We also lead efforts in research taking place at multiple different cities across the United States and the world. As you can imagine, studies spread out across such a big area require a lot of coordination and standardization. We design robust MRI and MRS methods to be used in clinical settings like these.

Another important question for our team is how early microstructural, chemical and functional changes can be detected in the brain and spinal cord by these advanced MR methods. We are interested in looking at these changes across all stages of disease.

Why does your group do this research?

The methods we use (MRI and MRS) can provide very helpful information to be used in clinical trials. These biomarkers we look at can provide quantitative information about how a disease is progressing or changing.

There is good evidence that subtle changes in the brain can be detected by these advanced MR technologies even before patients start having symptoms. If we better understand the earliest changes that are happening in the brain, this can in turn enable interventions at a very early stage. For example, we could treat people even before brain degeneration starts to take place.

Why did you form a research group connecting multiple labs?

We came together to form the CMRR Ataxia Imaging Team to benefit from our shared and complementary expertise, experience, and personnel. We can do more together than we could apart.

Are you recruiting human participants for research?

Yes, we are! We are looking for participants for multiple different studies. You can learn more about the research we are recruiting for at the following links: READISCA,  TRACK-FA, NAF Studies, and FARA Studies. More information is also available through the UMN Ataxia Center.

A photo of the CMRR Ataxia Imaging Team in 2016
A photo of the CMRR Ataxia Imaging Team in 2016, in front of the historic 4T scanner where the first functional MR images were obtained, in CMRR courtyard. Left to right – Christophe Lenglet (PI), Sarah Larson, Gulin Oz (PI), Dinesh Deelchand, Pierre-Gilles Henry (PI), James Joers, Diane Hutter

What Labs Make Up the CMRR Ataxia Imaging Team?

The Oz Lab

Principal Investigator:  Dr. Gulin Oz

Year Founded:  2006

Our focus is on MR spectroscopy, specifically neurochemistry and metabolism studies. We focus on spinocerebellar ataxias. Also, we have been leading MRS technology harmonization across different sites and vendors.

The Henry Lab

Principal Investigator: Dr. Pierre-Gilles Henry

Year Founded:  2006

We develop advanced methods for MR spectroscopy and motion correction. Then apply these new methods to the study of biochemistry and metabolism in the brain and spinal cord in various diseases. We have been working on ataxias since 2014.

Fun Fact about the Henry Lab: The French language can often be heard in discussions in our lab!

The Lenglet Lab

Principal Investigator:  Dr. Christophe Lenglet

Year Founded:  2011

We develop mathematical and computational strategies for human brain and spinal cord connectivity mapping. We do this using high field MRI. Our research aims at better understanding the central nervous system anatomical and functional connectivity. We are especially interested in looking at this in the context of neurological and neurodegenerative diseases.

Fun Fact

Members of our team have their roots in 7 countries (US, Turkey, France, India, Mauritius, South Korea, Ghana) and 4 continents (North America, Europe, Asia, Africa)

For More Information, check out the Center for Magnetic Resonance Research (CMRR) Website!


Written by Dr. Gulin Oz, Dr. Pierre-Gilles Henry, and Dr. Christophe Lenglet, Edited by Celeste Suart

Spotlight: The Kuo Lab

Principal Investigator: Dr. Sheng-Han Kuo

Location: Columbia University, New York, NY, United States

Year Founded:  2012

What disease areas do you research?

What models and techniques do you use?

Kuo Lab group photo.
This is a group picture of the Kuo Lab. From the left to right: Nadia Amokrane, Chi-Ying (Roy) Lin, Sara Radmard, Sheng-Han Kuo (PI), Chih-Chun (Charles) Lin, Odane Liu, Chun-Lun Ni , Meng-Ling Chen, Natasha Desai, David Ruff.

Research Focus

What is your research about?

We study how mishaps and damage in the cerebellum lead to the symptoms experienced by ataxia and tremor patients. By looking at human brains, as well as brains from mouse models, we study how different changes in brain structure can lead to symptoms. This includes how well different parts of the brain can communicate with each other.

Why do you do this research?

When you ask patients about the challenges living with ataxia or tremor, they will talk to you about their symptoms. Symptoms can make different activities of daily living very challenging! By connecting specific brain changes to specific symptoms, we want to develop treatment options that target specific diseases. By doing this, we hope to improve patient’s quality of life. 

Initiative for Columbia Ataxia and Tremor Logo. It is a circle containing a lion with its whiskers to look like a neuron

The Kuo lab is part of the Initiative for Columbia Ataxia and Tremor. It’s a new Initiative at Columbia University to bring a group of physicians, scientists, surgeons, and engineers to advance the knowledge of the cerebellum and to develop effective therapies for ataxia and tremor.

Are you recruiting human participants for research?

Yes, we are! We are looking for participants for clinical research and trials. You can learn more about the studies we are currently recruiting for at this link.

Fun Fact

In the Kuo Lab, we call ourselves “the Protector of the Cerebellum in New York City”.

For More Information, check out the Kuo Lab Website!

We are looking for new graduate students and postdoctoral researchers to join our team. If you are interested in our work, please reach out to us


Written by Dr. Sheng-Han Kuo, Edited by Celeste Suart

Snapshot: What is Neurogenesis?

Neurons are the cells that serve as building blocks of the nervous system. The brain contains an enormous variety of neurons, and they all need to get a start somewhere. The process by which neurons are formed is called neurogenesis.

An artist’s drawing of neurons in the brain. Photo used under license by Andrii Vodolazhskyi/Shutterstock.com.

When does neurogenesis happen?

Nearly all neurogenesis occurs before the age of 2 when the brain is in the early stages of being formed and refined. While most cells in the body are replaced as they wear out or get injured, neurons in the brain do not. By young adulthood, the brain has largely stopped making new neurons. Other than serving as an excellent reason to wear a helmet and otherwise protect your head from injury, this lack of new neuron formation doesn’t have a noticeable effect on how we go about our daily lives. After all, neurons are an incredibly adaptable cell type that readily change in response to a person’s environment and experiences.

In the past few decades, we have learned that there is an exception to the “all neurons are born early in life” rule. Some research has shown that new neurons can, in fact, be formed during adulthood in specific brain areas. For example, the hippocampus, a brain structure important for its role in forming and maintaining memories, continues to create neurons over the course of one’s life.

The purpose of these newly generated neurons is still debated. However, numerous studies have shown that neuron formation in the hippocampus is reduced in instances of psychiatric and neurodegenerative disorders. This includes certain types of ataxia like SCA1. This is thought to contribute to changes in cognitive function and mood, though the exact mechanisms are still being determined.

Why is neurogenesis interesting for the spinocerebellar ataxias (SCAs), aren’t these neurodegenerative disorders?

Since the discovery of neurodegenerative disorders, most research has focused on symptoms and how to delay symptom onset. This view sees neurodegenerative disorders, like the SCAs, as outcomes of mid to late-life when the toxic effects of mutant proteins become suddenly rampant. However, these disorders are caused by proteins that are present from the very earliest stages of brain formation.

In 2018, researchers studying SCA1 found that neurogenesis is increased in the cerebellum of young mice. This changed how the cerebellum communicates with the rest of the brain. This suggests that cerebellar function can be affected by more than neuronal loss. It could be of wider interest in the SCAs given the cerebellar dysfunction that is common between them. No research on cerebellar neurogenesis has been performed in other SCAs by this point. However, there are some indications that neurogenesis may also be altered in SCA2.

Additionally, Huntington’s Disease, a polyglutamine repeat disorder in the same disease family as several SCAs, has been shown to have increased neurogenesis in the cortex in both young mice and prenatal babies. The combination of these recent studies has made early neuron formation an area of key interest in the study of neurodegenerative disorders.

Current theories in the field contend that while the brain can compensate for changes in neuron numbers in early life, altered neurogenesis could be creating unique brain circuitry in individuals with known disorder-causing protein mutations. These changes could make them more vulnerable to neuronal dysfunction and neurodegeneration later in life.

Evidence for changed neurogenesis in SCAs, both early and late in life, adds a new layer of consideration to what we broadly think of as a mid- to late-life neurodegenerative disease. Additional research in coming years will hopefully provide more insight into how these additional facets of neural health may inform the development of new therapies.

If you would like to learn more about neurogenesis, take a look at these resources by the Queensland Brain Insitute and News-Medical.

Snapshot written by Carrie Sheeler and edited by Dr. Chloe Soutar.

Additional References

Cvetanovic M, Hu YS, Opal P. Mutant Ataxin-1 Inhibits Neural Progenitor Cell Proliferation in SCA1. Cerebellum. 2017 Apr;16(2):340-347. doi: 10.1007/s12311-016-0794-9. PMID: 27306906; PMCID: PMC5510931.

Shukla JP, Deshpande G, Shashidhara LS. Ataxin 2-binding protein 1 is a context-specific positive regulator of Notch signaling during neurogenesis in Drosophila melanogaster. Development. 2017 Mar 1;144(5):905-915. doi: 10.1242/dev.140657. Epub 2017 Feb 7. PMID: 28174239; PMCID: PMC5374347.

Xia G, Santostefano K, Hamazaki T, Liu J, Subramony SH, Terada N, Ashizawa T. Generation of human-induced pluripotent stem cells to model spinocerebellar ataxia type 2 in vitro. J Mol Neurosci. 2013 Oct;51(2):237-48. doi: 10.1007/s12031-012-9930-2. Epub 2012 Dec 9. PMID: 23224816; PMCID: PMC3608734.

Barnat M, Capizzi M, Aparicio E, Boluda S, Wennagel D, Kacher R, Kassem R, Lenoir S, Agasse F, Braz BY, Liu JP, Ighil J, Tessier A, Zeitlin SO, Duyckaerts C, Dommergues M, Durr A, Humbert S. Huntington’s disease alters human neurodevelopment. Science. 2020 Aug 14;369(6505):787-793. doi: 10.1126/science.aax3338. Epub 2020 Jul 16. PMID: 32675289; PMCID: PMC7859879.

Eliminación de la proteína ataxina-2 agregada como vía terapéutica para SCA2

Escrito por el Dr. Vitaliy Bondar Editado por el Dr. Hayley McLoughlin. Publicado inicialmente en el 5 de febrero de 2021. Traducción al español fueron hechas por FEDAES y Carlos Barba.

Una nueva investigación sugiere que la proteína ataxina-2 mutante abruma a las células en SCA2, lo que lleva a una disminución de la autofagia y la eliminación de las proteínas dañadas.

Se pueden hacer muchas comparaciones entre células y seres humanos. Al igual que los humanos, las células pueden acumular basura y desechos en ciertos momentos y este desorden con el tiempo se vuelve problemático e incluso tóxico. Esto es precisamente lo que Jonathan Henry Wardman y sus colegas de la Universidad de Copenhague decidieron investigar a nivel celular. Preguntaron si la falta de una eliminación adecuada de las proteínas defectuosas de la enfermedad afecta la supervivencia y el bienestar celular.

Los investigadores optaron por estudiar células derivadas de un paciente que tiene ataxia espinocerebelosa tipo 2 (SCA2). La causa de SCA2 es la expansión de la repetición CAG en el gen ATAXIN-2 , que codifica la cadena de aminoácidos de poliglutamina en una proteína de unión al ARN , ataxina-2. Se encuentra que la proteína ATXN2 expandida poliQ defectuosa se agrega dentro de la célula y las horas extraordinarias pueden afectar su supervivencia. La acumulación de productos proteicos agregados derivados de genes mutados es un sello distintivo de muchos tipos de ataxias espinocerebelosas, así como de otras formas de trastornos neurodegenerativos como la enfermedad de Parkinson.

No está claro cómo la agregación de proteínas afecta la supervivencia celular. Sin embargo, se han correlacionado múltiples defectos celulares con la agregación de ataxina-2. Por ejemplo, se ha informado que las mitocondrias que generan energía para una célula funcionan de manera anormal en modelos celulares SCA2. Además, un mecanismo de depuración celular, llamado autofagia , que es responsable de limpiar los compartimentos celulares defectuosos y ciertas proteínas rotas, se muestra menos eficaz en varios modelos de SCA2. Estos mecanismos los autores decidieron investigar en su artículo de investigación recientemente publicado.

scientist using microscope
Una nueva investigación que utiliza células SCA2 arroja luz sobre las causas de los síntomas de la enfermedad. Foto de Chokniti Khongchum en Pexels.com

Los científicos identificaron por primera vez la evidencia de disfunción celular SCA2 mediante la detección de una elevación significativa de los niveles de caspasa-9 y caspasa-8. Son proteínas que indican estrés celular y muerte. Los autores plantearon la hipótesis de que dicha disfunción celular puede deberse a la acumulación de ataxina-2 defectuosa. Para probar esta hipótesis, decidieron bloquear sistemáticamente dos vías celulares que procesan proteínas defectuosas: proteostasis y autofagia.

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Results of the RISCA study: gaining a better understanding of how ataxia symptoms first appear in at-risk patients

Written By Dr. David Bushart Edited by Celeste Suart

The RISCA study will help researchers design smarter, more efficient clinical trials by teaching us about the very early stages of SCA

Ataxia research has grown significantly in recent years. Although much work still remains, we are gaining a better understanding of how ataxia affects patients. Several exciting, new therapies are currently being studied. These advances would not be possible without the involvement of ataxia patients in clinical research studies. Some clinical studies are drug trials, where patients are enrolled to help researchers determine whether new therapies are effective at treating ataxia. However, other equally important types of clinical studies also exist. Ataxia patients play a critical role in the success of these studies.

What would an ideal treatment for ataxia look like? Ideally, we would be able to treat patients when their symptoms are very mild, or perhaps even before their symptoms appear at all. However, there are several obstacles to developing and testing this kind of hypothetical treatment:

First, it can be hard to know which patients to treat if symptoms are not yet present! There are many people who descend from patients affected by SCA of some kind. They have a 50% chance of being affected. While some of these people have been genetically tested, many have not. This makes it difficult to predict whether they will eventually develop SCA at all.

Second, along those lines, it could be very difficult to predict whether a drug is working to prevent symptoms from appearing if we don’t know precisely when symptoms should appear. It is much easier to tell if a drug is working when it is given to a patient with obvious symptoms – if their symptoms improve, the drug works.

Third, it can be difficult for researchers to enroll enough patients into clinical trials to get a meaningful result. This is complicated by the fact that we don’t know the answers to the first two questions above. Until recently, it remained unclear how a trial to test such a hypothetical treatment would need to be designed.

Thankfully, recent work has helped us better understand the answers to these questions. Results from the RISCA study were recently released. RISCA, which is a prospective, longitudinal, observational cohort study, was designed to study individuals who are at-risk for developing SCA, and how SCA symptoms might first appear.

Doctor and patient discussing something while sitting at the table
The RISCA study was designed to give doctors and patients more information about when ataxia symptoms first start to appear. This information is incredibly important for future ataxia clinical trials. Photo used under license by S_L/Shutterstock.com.
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