Building expertise

Impact of Clinical and Physiologic Heterogeneity on Kidney Function in Youth with Type 1 Diabetes

Aortic coarctation, a congenital malformation affecting approximately 1 in 2,500 individuals, is characterized by a narrowing of the aorta—the vessel through which the left ventricle ejects oxygenated blood to the body. Even after surgical or catheter-based repair, persistent stiffness of the aortic wall leads to arterial hypertension in nearly 50% of patients, with consequences for left heart function. Saïd Bichali aims to establish a link between cardiac work during exercise and physical fitness (VO₂max, an indicator of both athletic conditioning and effective blood circulation) in children, adolescents, and young adults who have undergone repair for aortic coarctation, compared with matched controls. Cardiac work during exercise can be estimated using echocardiography and a blood pressure cuff, while VO₂max is measured through respiratory gas exchange during exercise testing. The ratio between left ventricular work and VO₂max in aortic coarctation could serve as an early indicator of cardiac dysfunction and the risk of late complications such as arrhythmias and heart failure. This project will enhance understanding of cardiac function in aortic coarctation by identifying abnormalities that become apparent during exercise rather than at rest. The findings could guide future, individualized therapeutic strategies (antihypertensive medications, re-intervention to repair the aorta, or exercise retraining) and highlight the beneficial role of physical activity in optimizing cardiac performance.

Impact of Clinical and Physiologic Heterogeneity on Kidney Function in Youth with Type 1 Diabetes

Early signs of diabetic kidney disease (DKD) begin to emerge during adolescence and young adulthood in individuals with Type 1 Diabetes (T1D), making this a critical period for early detection and intervention. Antoine will investigate how the individual characteristics of youth with T1D influence the detection, progression, and treatment of DKD. Using a precision medicine framework, his project aims to examine factors associated with long-term trends in kidney function from adolescence to early adulthood, as well as differential responses to SGLT2i therapy, a therapy that helps block the reabsorption of sugar, according to markers such as insulin resistance and residual insulin production. Lastly, he will explore the application of machine learning algorithms to identify renal endotypes in T1D using clinical, metabolomic, proteomic, and genetic data. Together, these pillars aim to refine early detection and personalize treatment strategies for DKD in youth with T1D. 

Interneuron Transplantation for Developmental Epileptic Encephalopathies and Autism Spectrum Disorders

Proper brain function relies on a finely tuned balance between neuronal excitation and inhibition, largely maintained by interneurons. Although relatively few in number, these inhibitory cells play a crucial role in modulating oscillatory activity within neural networks. Alterations in their function are implicated in several neurodevelopmental disorders, notably developmental epileptic encephalopathies and autism spectrum disorders.Merrick Fallah’s project explores an innovative therapeutic approach based on the transplantation of interneuron (IN) precursors in two murine models of genetic disorders: developmental epileptic encephalopathy linked to the CACNA1A gene and autism associated with the MYO9B gene. Both models exhibit reduced interneuron populations, migration abnormalities, and impaired integration into cortical networks, leading to motor, cognitive, and behavioral deficits. By targeting a shared pathological mechanism, this project paves the way for a cross-cutting therapeutic strategy applicable to a range of disorders involving interneuron dysfunction. It could offer a new treatment perspective to improve the quality of life of affected children and their families.

Exploring the impact of child eating behaviours on cardiometabolic health: a longitudinal cohort study and randomized controlled trial 

Joseph’s research explores how eating behaviours in early childhood impact body weight and cardiometabolic health, particularly in the context of changes observed during the COVID-19 pandemic. Conducted through the TARGet Kids! practice-based research network, his work examines the relationship between eating behaviours, body mass index, and serum lipid trajectories over time. Joseph is also working with TARGet Kids! investigators on the Parents Together Trial, an embedded network randomized controlled trial, assessing whether a virtual parenting program led by public health nurses can improve eating behaviours and other markers of child health in preschool-aged children. By integrating longitudinal observational analyses with an innovative intervention, this research will provide evidence to inform public health programs and policies aimed at preventing childhood obesity and promoting long-term cardiovascular health. 

Hemodynamic and Functional Characterization of Pediatric Cerebral Arteriovenous Malformations (AVMs): the NeuroMAV Study

Cerebral arteriovenous malformations (cAVMs) are complex vascular anomalies characterized by abnormal high-flow connections between arteries and veins through a dysplastic nidus. In children, they represent the leading cause of intracerebral hemorrhage, often presenting with bleeding, higher mortality, and a greater risk of recurrence than in adults. However, risk factors identified in adults do not systematically apply to pediatric populations, and pediatric data remain limited. Moreover, the management of unruptured AVMs remains controversial due to the absence of pediatric clinical trials. The ARUBA study, which has influenced adult practice, did not include children and did not consider functional or hemodynamic parameters. This project aims to address this gap by characterizing the hemodynamic and functional profiles of ruptured and unruptured pediatric cAVMs using advanced imaging tools (4D Flow MRI, arterial spin labeling [ASL], and resting-state fMRI). This is the first project to propose an integrated approach to the pathophysiology of pediatric cAVMs. Its findings will enable the identification of biomarkers associated with rupture risk and support a personalized therapeutic approach based on imaging biomarkers rather than lesion anatomy alone.

Examining social determinants of mental health in diverse Canadian children and youth 

In Canada, one in five children and youth experience mental health challenges, yet large-scale studies often rely on clinical samples that underrepresent racialized, gender-diverse, and socioeconomically marginalized populations. This gap limits understanding of how mental health symptoms manifest across intersecting social identities and contexts and may obscure disparities in access to care. Roxy’s research uses the Spit for Science dataset, Canada’s largest community-based paediatric mental health cohort, with over 40,000 participants, to investigate how gender identity, race, ethnicity, and material deprivation interact to influence mental health traits. By focusing on traits rather than diagnoses, this work captures children and youth who may not receive formal clinical attention despite experiencing significant symptoms. The findings will generate inclusive, equity-focused evidence to inform early identification, intervention strategies, and policy reforms aimed at creating a more equitable paediatric mental health system.

Defining mechanisms of GLI3 variant associated renal malformation in Pallister-Hall Syndrome

Congenital anomalies of the kidney and urinary tract (CAKUT) are typically genetic in origin, highly phenotypically varied, and lack genotype-phenotype correlation. This suggests that pathogenesis in monogenic CAKUT is a product of genetic variant-specific mechanisms, unique to every patient – however, no such mechanisms are presently known. Dina’s work aims to fill this knowledge gap, as it hinders clinicians’ diagnostic and prognostic capacities, and prevents the development of precision therapies for CAKUT.

She is investigating variant-specific mechanisms that drive CAKUT in Pallister-Hall Syndrome, a rare genetic disorder that affects the development of many parts of the body. This study is the first to interrogate genotype-phenotype correlation in a monogenic form of CAKUT by characterizing a series of patient-specific genetic variants, with the aim of improving prognosis an development of precision therapies.

Synchronization of Bodies, Hearts, Brains and Lived Experiences in Autism: Social Interaction Multimodal Study contributing to Precision Diagnoses 

Anne Monnier’s project is part of the research carried out by the Precision Psychiatry and Social Physiology laboratory, headed by Pr. Guillaume Dumas. 

It aims to enrich our understanding of autism by exploring the atypical synchronization dynamics during social interactions. This innovative research uses multi-brain and multi-body “hyperscanning” to analyze dimensions neglected in biomedical research of autism: social interaction and lived experience. Unlike previous models which focus on individual deficits, this project suggests turning the spotlight on the dimension of interaction with others in a multimodal model which also integrates the interlocutor’s dynamics. Coordination of movements, cardiac coherence, cerebral synchronization and coherence of the personal feeling of connection to others will be four modalities studied with 80 dyads of neurotypical or autistic children interacting with their parents. The aim is to determine whether a detailed characterization of these interactions, with different mechanisms, can contribute to more precision diagnoses. 

Efficient Machine Learning Methods to discover the Determinants of Immune Protection against Cytomegalovirus Infection

This research project focuses on the development of advanced machine learning and bioinformatics methods to better understand the mechanisms of immune protection against cytomegalovirus (CMV) infection, a common congenital infection and the leading cause of deafness and neurodevelopmental disorders in children. Using massive, ultra-dimensional data from cutting-edge technologies such as third-generation sequencing and phage immunoprecipitation sequencing, the team will analyze viral genomes and immune responses within well-characterized longitudinal cohorts to identify the characteristics of CMV strains capable of bypassing pre-existing immunity and causing mother-to-child transmission.

This project is designing machine learning models to identify reinfections during pregnancy, to intervene and prevent fetal transmission. In addition, they aim to define mutations that enable reinfection and identify better vaccines targets among CMV variants. These efforts will help guide the development of precision vaccines that offer broad protection against multiple viral strains in mothers and children. The tools created by this project could also be adapted to other viruses, strengthening the public health response to emerging viral threats. 

Advancing molecular characterization and diagnostics of pediatric neurodevelopmental disorders through long-read sequencing

Mengqi’s work investigates four rare pediatric neurodevelopmental disorders (NDDs) – Kabuki, CHARGE, Sotos, and Tatton-Brown-Rahman syndromes, known for their phenotypically complex and highly variable clinical presentations. These syndromes are characterized by intellectual disability, growth dysregulation, and congenital anomalies, emphasizing the crucial connection between epigenetic regulation and neurodevelopment. The clinical overlap among these syndromes presents challenges for early-life diagnosis, highlighting the need for a deeper exploration of epigenetic markers to enhance both understanding and clinical management.

Previous research has successfully identified syndrome-specific DNA methylation signatures for over 60 NDDs, providing valuable insights into their pathophysiology and aiding in diagnosis. However, these findings have been constrained by the limited coverage of specific genomic regions available in the EPIC array platform. To address this limitation, this study aims to leverage long-read sequencing (LRS), an emerging technology capable of capturing both novel genomic variants and epigenomic information across the entire genome. The application of LRS will provide unprecedented insights into DNA methylation landscapes and alterations in pediatric NDDs, leading to expanded diagnostic capabilities and phenotype-epigenotype-genotype correlations. Early identification of epigenetic markers may facilitate predictive diagnostics and targeted therapeutic interventions, significantly impacting patient outcomes.

PCHP Scholars

Dr. Ashish Deshwar, Precision Child Health Scholar in Translational Genomics

LDr. Deshwar’s research program is committed to reaching a genetic diagnosis for all children seen at the hospital through utilizing the latest technological advances and applying them to rare disease. His work represents the critical application of research technologies into the clinic, driving the PCH movement through three areas of interest: 

•  Zebrafish models of new genetic diseases: In some cases, where a new potential disease gene is identified, Dr. Deshwar’s group develops a zebrafish model to help describe an entirely new disease, providing a diagnosis for the patient and creating a model where you can then study the disease mechanisms and develop therapies. 
• Leveraging a multi-omics approach for genetic diagnosis: Using technologies like RNA sequencing and proteomics (study of proteins) to complement the DNA studies we do; we can better understand and interpret the consequence of the genetic changes seen in children.  
• Bespoke functional assays: By using established molecular biology techniques in a personalized, or “bespoke” fashion, we can design highly individualized tests (i.e. a test created specifically for a child seen at the hospital) to assess the impact of an individual’s genetic change

This work is an important prelude to the next step in a patient’s journey – delivering individualized treatment. To design effective precision therapies, we first need to reveal and understand the complexity of the diagnosis.  

Training or Fellowship opportunities

The Precision Health Scholarship Program is one of the flagship initiatives of the Partnership, aimed at funding innovative research and training the next generation of researchers.

Upcoming opportunities