Veronique Belzil, Ph.D., M.S., works on developing individualized approaches to treating amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD) and other related neurodegenerative diseases. Her laboratory aims to discover and characterize genetic, epigenetic and transcriptional changes driving neuronal death to better understand the complex etiology, heterogeneous clinical presentation, comorbid conditions and multifaceted environmental interaction observed in patients with neurodegenerative diseases.
Dr. Belzil's research group uses human biospecimens and integrative multiomic approaches to systematically identify disease-specific variants, elucidate their underlying mechanisms of action, shed light on distinct circuitry, and ultimately uncover static and dynamic biomarkers and putative therapeutic targets. Her lab also works on developing therapeutic approaches using gene delivery, gene silencing, gene editing and RNA interference methods in patient-derived cell lines.
- Genetic, epigenetic and transcriptional changes in ALS and FTD. While current findings suggest shared pathogenesis between ALS and FTD, the mechanistic basis of their shared and distinct circuitry remains unknown at the molecular level. Dr. Belzil systematically profiles genetic, epigenetic and transcriptional alterations at single-cell resolution, in bulk tissues, and in sorted cell populations from C9orf72-associated and sporadic postmortem brain and spinal cord samples. She integrates the resulting data sets using machine learning and other advanced computational approaches to identify common and distinct genes, regulatory sites and biological pathways altered in ALS and FTD.
- ALS in military veterans. Military veterans are at greater risk of developing ALS, and this group of patients offers a unique opportunity to shed light on the biological mechanisms that may be applicable to the broader sporadic ALS (sALS) population. Dr. Belzil generates multilevel signature profiles of different brain regions in ALS to gain a better understanding of motor neuron vulnerability and sALS-specific brain circuitry.
- Identification of biomarkers and development of clinical tests. Identification of biomarkers to facilitate early diagnosis, predict prognosis, stratify patients, identify surrogate endpoints and assess target engagement during clinical trials would be groundbreaking for ALS and FTD. Dr. Belzil generates signature profiles of different biofluids to identify unique variants that can be used for the development of clinically relevant biomarker panels.
- Identification of therapeutic targets and development of patient-centered therapeutic approaches. For approximately 82% of ALS patients and approximately 73% of FTD patients, their disease is genetically unexplained. Dr. Belzil studies disease-associated loci identified through genome-wide association studies and multiomic profiling in patient-derived cell models (immortalized lymphocytes, fibroblasts and iPSCs) using gene delivery, gene silencing, gene editing and RNA interference methods. She seeks to identify needed therapeutic targets and works closely with the Mayo Clinic Department of Neurology to quickly bring her findings from bench to bedside.
Significance to patient care
ALS and FTD are devastating and fatal neurodegenerative diseases that strike middle-aged adults just as they reach full familial, financial and career potential. A diagnosis of ALS or FTD is distressing for both patients and their loved ones, and is socially and economically detrimental for global health systems: There is no treatment to prevent, decelerate or stop neuronal death in these patients.
ALS is the most common motor neuron disease, with more than 200,000 individuals affected each year worldwide, while FTD is the second most common dementia in people under 60 years old (after Alzheimer's disease), affecting more than 900,000 individuals each year worldwide. While initial symptoms lead to the diagnosis of either FTD or ALS, up to 50% of patients eventually develop symptoms of the other disease, with 13% to 15% ultimately receiving both diagnoses. While these findings suggest shared pathogenesis, the mechanistic basis of their shared and distinct circuitry remains unknown at the molecular level, no reliable biomarkers have been identified, and no effective treatment currently exists.
- Recipient, Career Development Award, Gerstner Family Foundation, 2020-2022
- Recipient, Career Development Award, LiveLikeLou Foundation, 2020-2021
- Recipient, Career Transition Award, ALS Canada-Brain Canada, 2016-2018
- Recipient, Milton Safenowitz Postdoctoral Award, ALS Association, 2014-2016
- Recipient, Postdoctoral Award, Canadian Institutes of Health Research, 2012-2015