Vania Prado
Professor
D.D.S. University of Itauna, Brazil
M.Sc.Federal University of Minas Gerais, Brazil
Ph.D. Federal University of Minas Gerais, Brazil
Post-Doctoral Fellowship: McGill University
Office: Robarts Research Institute
p. 519.661.2111 x86827
f. 519.850.2562
e. vprado@robarts.ca
Visit: Dr. Prado at Robarts Research Institute
Academic Journey
I went into dentistry right out of high school but chose not to go into practice after graduating. Instead, I pursued a Master’s in Biochemistry at the Brazil Federal University of Minas Gerais in Brazil, which transitioned into a PhD. During my PhD, I focused on identifying maternal proteins in amniotic fluid. The work made extensive use of two-dimensional gels, immunoblots and other protein analyses techniques. After completing my PhD, I joined McGill University for a postdoctoral fellowship where I focused on studying the Y chromosome using molecular biology. At the time, I performed daily manual DNA sequencing, as this was before PCR became widely used.
Why Science (or Why Research)?
I have always been curious, and thoroughly enjoyed the first two years of dental school, which were filled with basic sciences like physiology, biochemistry, and biology. This is what I really loved, and it sparked my fascination and desire to learn more. I realized I was particularly curious about how cells and organ’s function, with a particular interest in understanding the brain. How can biochemical reactions translate into thoughts and actions? I found professional school challenging, not because of academics, but because of the routine nature of the work. The repetitive tasks felt tedious and unfulfilling. In contrast, exploring biochemistry and physiology fuels my curiosity and passion. It is a constant journey of asking questions and seeking answers – something entirely different from dentistry.
Research/Teaching Goals
My main goal is to understand how the brain functions and what goes wrong in neurodegenerative diseases, with a focus on Alzheimer’s and Parkinson’s disease. In my lab, we use mouse models to investigate these disorders. We generate various genetically modified mouse lines by altering specific genes that we are interested in, to study the resulting molecular and behavioral changes. We employ a diverse range of genetically modified mouse models to explore specific aspects of these diseases. Using state-of-the-art molecular, behavioural, and imaging techniques, we identify the changes caused by these genetic modifications. Because our focus is on neurodegenerative diseases, we place a strong emphasis on employing robust and translatable cognitive tests. We use tasks that are automated and closely resemble those used in humans, enabling us to assess whether the changes observed in mice reflect similar phenomena in humans. Additionally, we use fluorescent probes to monitor neuronal communication in different brain regions while the animals perform behavioral tasks. This allows us to understand how changes in neuronal communication lead to alterations in behavior. This integrated approach helps us uncover molecular pathways critical for brain function and evaluate potential drugs to treat the deficits observed in the mutant animals.
Specific Research Interests
My research focuses on understanding neuronal communication in health and disease, with particular focus on Alzheimer’s, Parkinson’s, and prion diseases. One of my main interests is to understand the role of the cholinergic system in modulating brain function, especially in Alzheimer’s disease (AD). To study this, we have generated mutant mice with altered expression of the vesicular acetylcholine transporter (VAChT), which regulates pre-synaptic cholinergic signalling. These models allow us to study the function of specific neurons that secrete acetylcholine (ACh).
Using genetic, behavioral, molecular and pharmacological approaches our group has uncovered new mechanisms controlled by specific cholinergic circuits. For instance, we demonstrated that VAChT-deficient mice exhibit symptoms of myasthenia and have deficits in object and social recognition. Additionally, we dissected the role of acetylcholine-glutamate co-transmission in the striatum, which involved combining brain probes with touchscreen-based behavioral tests to measure subsecond changes in acetylcholine and dopamine release during cognitive tasks.
As cholinergic neuron degeneration is a hallmark of AD, we have generated mice with reduced VAChT levels in cholinergic neurons that project to hippocampus and cortex to explore the specific effects of reduced cholinergic signaling. Them mice exhibit many features of AD, including minimal ACh release in the cortex and hippocampus, abnormal hippocampal synaptic plasticity, progressive hippocampal degeneration, and multiple cognitive deficits. Notably, we found that VAChT deficiency worsens plaque pathology in male AD model and ovariectomized females but not in ovary-intact female mice. Conversely, VAChT over-expression reduces plaque pathology in males but not in ovary-intact females, revealing a sex-specific role for cholinergic regulation in AD progression.
Our current work uses advanced mouse models of Alzheimer’s and Parkinson’s diseases, in which mouse genes are replaced with human equivalents. We also employ cutting-edge techniques like brain clearing, which makes whole mouse brains transparent, and light-sheet microscopy, enabling high-resolution 3D imaging of brain structures. My lifelong commitment is to advance the understanding and treatment of brain disorders through innovative research and the development of novel mouse models.
Undergraduate Teaching:
4380b – Neuropharmacology (Course coordinator and Instructor)
4980- Seminar Research and Project (Supervisor)
Graduate Teaching:
5561- Dentistry (Instructor)
9500A – Neuroscience (Instructor)
Most Rewarding Moments
One of the most rewarding aspects of my career is witnessing the success of my trainees. Watching them grow into accomplished scientists and make meaningful contributions to the field is incredibly fulfilling. Their achievements underscore the importance of mentorship in shaping the next generation of researchers.
Equally gratifying is knowing that my work is recognized by the scientific community and holds the potential to improve lives. This recognition inspires me to continue pushing boundaries in the quest to better understand and treat brain disorders.
The collaborative environment at Western University has also been a significant source of fulfillment. I work closely with three other principal investigators, essentially functioning as a single lab. This collaboration extends to experts from Western and institutions like McGill University and the University of Toronto. Together, we have achieved so much, and this collective effort stands as one of my proudest accomplishments. Being part of such a dynamic and productive team is truly rewarding.
Advice to Students
Follow your passion!! Choose something you truly love, because when you enjoy what you do, it won’t feel like work. You’ll be motivated to put in the effort, even during late nights or weekends, and that dedication will help you excel. Loving what you do is the key to success.
Interests Outside of Academia
I enjoy paint-by-number crafts—they're a fun and relaxing way to unwind! I’ve also been learning French on Duolingo for the past four years and am proud to have a streak of over 1,400 days. In addition, I love biking and reading, which keep me active and inspired.
Awards and Recognitions:
Special Visiting Researcher - Science without Borders (UFMG, Brazil) (2015-17)
USC Teaching Honour Roll award for teaching in Physiology and Pharmacology (2015-16)
Research award - Senior Fellowship - National Research Council in Brazil
Research award - Junior Fellowship - National Research Council in Brazil
Highlighted Publications:
Sex-dependent cholinergic effects on amyloid pathology: A translational study.
German-Castelan L, Shanks HRC, Gros R, Saito T, Saido TC, Saksida LM, Bussey TJ, Prado MAM, Schmitz TW, Prado VF; Australian Imaging Biomarkers and Lifestyle flagship study of ageing.Alzheimers Dement. 2024 Feb;20(2):995-1012. doi: 10.1002/alz.13481. Epub 2023 Oct 17.PMID: 37846816
Skirzewski M, Princz-Lebel O, German-Castelan L, Crooks AM, Kim GK, Tarnow SH, Reichelt A, Memar S, Palmer D, Li Y, Jane Rylett R, Saksida LM, Prado VF, Prado MAM, Bussey TJ. Nat Commun. 2022 Dec 24;13(1):7924. doi: 10.1038/s41467-022-35601-x.PMID: 3656438
Chronic hM3Dq signaling in microglia ameliorates neuroinflammation in male mice.
Binning W, Hogan-Cann AE, Yae Sakae D, Maksoud M, Ostapchenko V, Al-Onaizi M, Matovic S, Lu WY, Prado MAM, Inoue W, Prado VF.Brain Behav Immun. 2020 Aug;88:791-801. doi: 10.1016/j.bbi.2020.05.041. Epub 2020 May 17.PMID: 32434046
Cholinergic Surveillance over Hippocampal RNA Metabolism and Alzheimer's-Like Pathology.
Kolisnyk B, Al-Onaizi M, Soreq L, Barbash S, Bekenstein U, Haberman N, Hanin G, Kish MT, Souza da Silva J, Fahnestock M, Ule J, Soreq H, Prado VF, Prado MAM.Cereb Cortex. 2017 Jul 1;27(7):3553-3567. doi: 10.1093/cercor/bhw177.PMID: 27312991
Kolisnyk B, Al-Onaizi MA, Hirata PH, Guzman MS, Nikolova S, Barbash S, Soreq H, Bartha R, Prado MA, Prado VF. J Neurosci. 2013 Sep 11;33(37):14908-20. doi: 10.1523/JNEUROSCI.1933-13.2013.PMID: 24027290
Prado VF, Martins-Silva C, de Castro BM, Lima RF, Barros DM, Amaral E, Ramsey AJ, Sotnikova TD, Ramirez MR, Kim HG, Rossato JI, Koenen J, Quan H, Cota VR, Moraes MF, Gomez MV, Guatimosim C, Wetsel WC, Kushmerick C, Pereira GS, Gainetdinov RR, Izquierdo I, Caron MG, Prado MA.Neuron. 2006 Sep 7;51(5):601-12. doi: 10.1016/j.neuron.2006.08.005.PMID: 16950158
See Publications by Vania Prado on PubMed
