Azrieli Accelerator Impact

Precision engineering of the gut microbiome to support people with neurodevelopmental conditions

Principal Investigator: Dr. Erik Bakkeren, PhD, Biological Sciences, Faculty of Science 

We are becoming increasingly aware of how the trillions of microbes that colonize our bodies, the human microbiome, influence the onset, severity, and likelihood of developing neurodevelopmental disorders (NDDs). This project will explore a route to stably introduce a therapeutic microbe, Limosilactobacillus reuteri, into gut microbiomes to ameliorate symptoms that co-occur with autism spectrum disorder (ASD). This will provide a map between microbiome composition, the introduction of a therapeutic microbe, and how it affects behaviours in ASD using mouse models.  

Engineering Microbial Therapeutics to Modulate the Gut-Brain Axis in Neurodevelopment

Principal Investigator:  Dr. Xiaofan Jin, PhD, Assistant Professor, Biomedical Engineering, Schulich School of Engineering 

Collaborators: Dr. See-Yeun Ting, Dr. Pina Colarusso, Dr. Tom Louie, Dr. Marie-Claire Arietta 

This research project investigates how the gut microbiome may influence early brain development and explores a new precision approach for targeting harmful gut bacteria linked to neurodevelopmental conditions. The study focuses on Klebsiella, a bacterial group associated with immune dysregulation, neuroinflammation, and white matter brain injury, which can contribute to conditions such as cerebral palsy, learning disabilities, and sensory impairments. The project will test whether a targeted microbiome-editing strategy can safely reduce harmful bacteria linked to adverse neurodevelopmental outcomes.

Uncovering brain pathways to improve motor function in Fragile X Syndrome

Principal Investigator: Dr. Patrick Whelan, PhD, Professor, Physiology and Pharmacology/Clinical Neurosciences, Cumming School of Medicine; Faculty of Veterinary Medicine; Faculty of Kinesiology 

Co-applicants/Collaborators: Dr. Ning Cheng, Dr. Ray Turner
Research team: Dr. Jonathan Milla-Cruz, Postdoctoral Fellow 

This research project investigates the brain mechanisms underlying motor difficulties in Fragile X syndrome (FXS), a common inherited neurodevelopmental condition associated with hyperactivity, poor coordination, gait instability, and low muscle tone. Using advanced techniques, the project will examine how altered brain signaling and imbalances between excitatory and inhibitory neural activity contribute to motor dysfunction and anxiety-related behaviours in FXS. The research aims to uncover new circuit-based therapeutic targets and lay the groundwork for future treatments to improve motor function and quality of life for individuals with Fragile X syndrome.

Understanding the HACE1 Ubiquitin Ligase in Early Brain Development

Principal Investigator: Dr. Mateusz (Mats) Ambrozkiewicz, PhD, Associate Professor, Tier II Canada Research Chair in Childhood Neurodevelopment, Biochemistry and Molecular Biology, Cumming School of Medicine 

Collaborator: Dr. Sonja Lorenz, Max Planck Institute for Multidisciplinary Sciences

This research project investigates how the cerebral cortex - the part of the brain responsible for learning, perception, and decision-making - develops during embryonic life. The work focuses on HACE1, a protein linked to rare neurodevelopmental conditions associated with intellectual disability, epilepsy and developmental delays. By studying how HACE1 helps guide the formation of early brain circuitry, this research aims to advance understanding of neurodevelopmental conditions and lay the groundwork for future therapeutic strategies. 

Tracing how ancient viral DNA, the immune system and gut microbes shape brain development in children with FASD

Principal Investigator: Dr. Ann Gregory, PhD, Assistant Professor, Tier II Canada Research Chair in Viromics and One Health, Biological Sciences, Faculty of Science

Co-applicant: Dr. Tamara Bodnar, Collaborator: Shari Filipionek 

This research project explores how interactions between human endogenous retroviruses (HERVs), ancient viral DNA embedded in the human genome, the immune system, and the gut microbiome may contribute to differences in neurodevelopmental outcomes in children with fetal alcohol spectrum disorder (FASD). Although prenatal alcohol exposure is known to affect brain development, children with similar exposure histories can experience very different cognitive and behavioral outcomes, and the biological reasons for this variability remain unclear. By identifying potential links between HERV activity, microbiome-associated immune responses and neurodevelopment, the project aims to uncover new biological pathways involved in FASD and lay the groundwork for future strategies to better predict risk and support targeted interventions. 

Clinician-in-the- loop AI tools to support independent communication for nonspeaking autistic individuals

Principal Investigator: Dr. Diwakar Krishnamurthy, PhD, Professor, Electrical and Software Engineering, Schulich School of Engineering

Collaborators: Dr. Vikram. K. Jaswal, Dr. Kristen Gillespie-Lynch, Sarah Safton, and Dr. Chandra Lebenhagen 

This research project aims to improve access to personalized communication support for nonspeaking autistic individuals by developing a clinician-guided AI practice app that helps build independent typing and spelling skills. We will develop and pilot a low-cost, clinician-in-the-loop AI practice system that extends expert support into between-session practice while respecting sensory-motor needs and maintaining clinician oversight. The findings will help lay the foundation for scalable, accessible communication technologies that extend expert support beyond the clinic and increase opportunities for expressive communication and participation in daily life. 

Brain Health Vulnerability During Menopause in Women with ADHD: A Pilot Project

Principal Investigator: Dr. Brandy Callahan, PhD, Associate Professor, Tier II Canada Research Chair in Adult Clinical Neuropsychology, Psychology, Faculty of Arts 

Collaborators: Meike Boerstra, Dr. Cindy K. Barha, Dr. Eric E. Smith, Dr. Zahinoor Ismail, Dr. Jason Hassenstab 

Women’s brain health is significantly impacted by perimenopause, a transitional period lasting up to 10 years. “Brain fog” and mood changes are very common perimenopausal symptoms, and have been linked to reduced frontal, temporal and hippocampal brain volumes, indicating that female brains are actually restructured during the menopausal transition. New data suggest that perimenopause may be more challenging for women with attention-deficit/hyperactivity disorder (ADHD) but its impacts on brain health have not been directly examined. The proposed pilot project will unfold alongside a larger research project studying the hormonal experiences of female youth with ADHD and will build complementary knowledge about the lifespan impacts of hormonal fluctuations in ADHD. Ultimately, this work will catalyze larger, more ambitious investigations into the brain health of women who are aging with ADHD. 

Understanding differences in Au-Kline syndrome severity and variability through patient cell phenotyping

Principal Investigator: Dr. Ping-Yee (Billie) Au, MD, PhD, Clinical Associate Professor, Medical Genetics, Cumming School of Medicine

Co-applicants: Dr. Pina Colarusso, Dr. Timothy Shutt

This research project investigates how mutations in the HNRNPK gene disrupt brain development and contribute to HNRNPK-related neurodevelopmental disorder (also known as Au-Kline syndrome), a rare condition associated with intellectual disability, brain malformations, and neuromuscular challenges. By comparing cellular changes across variant types and in both fibroblasts and neuron-like cells, the project aims to uncover the biological mechanisms driving disease severity and variability. The findings will help identify potential therapeutic targets, improve diagnosis and prognostic tools, and establish a foundation for future drug screening and precision treatments for affected individuals.