Every Bright Young Scientist: Meet Dr. Veronique Belzil

Meet Dr. Veronique Belzil, an Assistant Professor in the Department of Neuroscience at Mayo Clinic College of Medicine in Jacksonville, Fla., and a former ALS Association Milton Safenowitz Postdoctoral Fellow. Having been personally touched by ALS, she is extremely dedicated to finding treatments and ultimately a cure for this devastating disease.

Her work focuses on sporadic ALS, which is a type of ALS that is not genetically inherited and accounts for approximately 90% of all ALS cases. We are proud to report her recent successes of identifying new ALS genes and disease pathways that can be targeted for developing potential ALS therapeutics. This important work was published in August in the journal Acta Neuropathologica. Read more about Dr. Belzil’s extraordinary work, her vision for the future of ALS research, and what she is up to now.

Thank you for joining us today! You received an ALS Association Milton Safenowitz Postdoctoral Fellowship back in 2014. How has Fellowship helped your research and career?

The Milton Safenowitz Postdoctoral Fellowship enabled me to develop the new ALS epigenetic program at Mayo Clinic Jacksonville. The aim of the project supported by the fellowship was to generate gene regulation and expression profiles of two different brain regions in ALS. Using advanced computational technologies, we identified altered biological pathways in disease that have the potential to be targeted by therapeutics.

“Without the support of donors, our work in basic and translational research would not be possible. We are extremely grateful for everybody’s generosity. The portion of money attributed to research not only contributes to a better understanding of this devastating disease, but also paves the way to develop effective therapeutics. Hopefully, because of the collaborative effort of researchers in the field and the financial support of donors, ALS will be a curable and preventable disease in a very near future.” – Dr. Veronique Belzil

Note: Epigenetics is the study of a person’s inheritable traits or characteristics impacted by gene expression (whether a gene is active or inactive) that does not involve changes in a person’s underlying DNA sequence.

Why do you love working in ALS research?

ALS has profoundly impacted my life, having lost a loved one to the disease in 2000. In 2007, I started my Ph.D. and dedicated my career to ALS research, hoping to positively impact patient and their family members’ lives. Today, I remain devoted to understanding the biological mechanisms that drive this devastating, currently incurable disease, to facilitate developing effective therapeutics. In addition to my research, I also initiate and participate in fundraising and awareness campaigns through events for The ALS Association and its Florida Chapter, the ALS Society of Quebec and Canada, and others. Regularly volunteering motivates my research and has been central to my personal and professional development. Having regular contact with patients, caregivers, and ALS advocates inspires my work and sharpens my will and determination to find a cure.

Congratulations on the publication of your paper! Please explain the major results of your published project.

The primary goal of our study was to better understand the biological processes leading to gene misregulation in the brain of ALS patients. We used two different brain regions (frontal cortex and cerebellum) from patients who agreed to donate their brains after death. We found that thousands of genes are regulated differently in sporadic ALS (not inherited) and C9orf72-associated ALS when compared to normal brains. Dr. Ebbert and I also found that, while some changes overlapped between sporadic and C9orf72-associated ALS patients, each disease group had largely distinct gene regulation and expression profiles. Finding similarities among sporadic ALS patients was especially interesting, because this is the largest ALS patient group, and the underlying cause of sporadic ALS is not well understood. These patients were simply grouped based on the facts that their cases were unexplained genetically and had no other family members affected with either ALS or dementia. Combining the results generated from the two different profiles (gene expression and gene regulation profiles) permitted the identification of multiple new genes involved in disease. Among these, SERPINA1, a gene normally expressed in the liver and blood, was increased in ALS brains. This suggests that brain cells may not tolerate increased SERPINA1 gene expression. We also found that SERPINA1 contributes to many critical cellular and molecular functions, and interacts with different molecules that have been previously linked to ALS.

What is the impact of your research?

We were able to identify new genes contributing to disease, like SERPINA1, that can potentially be targeted by therapeutics. We also identified novel cellular functions that are perturbed in ALS, which can be further explored by other research groups to develop therapies.

What are your next steps for this project?

Dr. Ebbert and I are planning to characterize the key players we identified to better understand how these changes affect the brain circuitry in ALS patients. In other words, we will determine how regulatory changes in a few genes, lead to dysfunction of other genes, and consequently disrupt normal biological processes essential for brain cell health.

What are the future goals of your research?

There are so many aspects of ALS that still need to be explored. What especially intrigues me is that only 5-8% of overall ALS cases report other affected family members, with significant clinical complexity among these members. Moreover, the fact that the known genes associated with familial (e.g. inherited) ALS remain mostly unaltered in sporadic (e.g. not inherited) ALS patients points to other likely disease culprits. My goal is to better understand the role of altered gene regulation in ALS, specifically in sporadic ALS, the most common form of ALS. I want to assess whether these alterations can be targeted by therapeutics.

Gene expression is regulated by the inherited but dynamic epigenome, whose job is to turn genes on and off; thereby, determining whether a gene is made into protein and ultimately whether the generated proteins are critical for cell survival. Such epigenetic regulation is mediated by cellular needs, environmental influences, and other factors such as diet, exercise, and aging. These characteristics make epigenetic changes great candidates to explain not only the variation in clinical presentation we observe across family members carrying the same mutation, but also the development of genetically unexplained sporadic ALS. The ultimate goal is to identify unique sporadic profiles in the general population and start preventive treatment before disease onset. In summary, my research aims to better understand the role of the epigenome in leading to neuronal death, and translate these findings into treatment.

I know you since have finished your Fellowship. What are you doing now?

I am currently an Assistant Professor in the Department of Neuroscience at Mayo Clinic College of Medicine in Jacksonville, Florida. I am also an Adjunct Professor in the Department of Neurology and Neurosurgery at McGill University in Montreal, Quebec, Canada.

What do you like to do for fun outside the lab?

I spend all my time outside the lab with my family. My 11 and 13-year-old daughters most certainly keep my husband and I busy! In addition to school, we run from ballet and vocal rehearsals to different performances they often give. When not driving around town, our family loves hiking with our dog, playing board games, preparing delicious meals together, or simply relaxing watching movies with our three cats!

Thank you Dr. Belzil for taking the time to sit down with us today. We are so pleased to hear how well your research is progressing and your promotion to Assistant Professor, which are tremendous accomplishments. Please keep us informed of all your future successes.

Read more about Dr. Belzil’s project here and here.

Donate today to support ALS research and bright, young scientists like Dr. Belzil.2017-EDAU-donate-button

Paper citation:

Conserved DNA methylation combined with differential frontal cortex and cerebellar expression distinguishes C9orf72-associated and sporadic ALS, and implicates SERPINA1 in disease.

Ebbert MTW, Ross CA, Pregent LJ, Lank RJ, Zhang C, Katzman RB, Jansen-West K, Song Y, da Rocha EL, Palmucci C, Desaro P, Robertson AE, Caputo AM, Dickson DW, Boylan KB, Rademakers R, Ordog T, Li H, Belzil VV.

Acta Neuropathol. 2017 Aug 14. doi: 10.1007/s00401-017-1760-4. [Epub ahead of print]

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