Call for Mats Sundin Fellowship in Human Developmental Health KI 2025 - part 2

Lab website: https://howeandfishlabs.com/
Department and Institution: Laboratory Medicine and Pathobiology, Toronto General Hospital Research Institute - University Health Network
Email Address: jason.fish@utoronto.ca
 

Topic Area:
Uncovering the developmental origins of brain arteriovenous malformations:
Brain arteriovenous malformations (bAVMs) are abnormal direct connections between arteries and veins that bypass a capillary network. Because high pressure blood directly shunts to an artery, these vessels remodel over time and become a tangled lesion that is prone to rupture. Indeed, these lesions are the leading cause of hemorrhagic stroke in young people We recently discovered that the majority of patients with bAVMs have somatic activating mutations in KRAS. These mutations are found in the endothelial cells that line these lesions (Nikolaev et al, New England Journal of Medicine, 2018). We went on to demonstrate that expression of activated KRAS in the endothelium can result in bAVMs in zebrafish and mouse models (Fish et al, Circulation Research, 2020). It remains unknown when somatic mutations occur and how these mutant cells clonally expand to result in pathology later in life. It is thought that these mutations occur during vascular development and expand over time. Our ongoing work is seeking to identify how somatic mutations in KRAS lead to vessel remodeling. We have recently found that KRAS mutations alter metabolism in endothelial cells and induce cell competition between mutant and wild-type cells. Using cell culture, zebrafish and mouse models, together with human bAVM samples, we will further uncover the mechanisms involved. Furthermore, we will seek to discover directed therapies based on the specific KRAS mutations in individuals with bAVMs. This work will transform our understanding of the developmental origin of these lesions and will uncover new treatment options.

Lab website: https://thedonnellycentre.utoronto.ca/faculty/aleksandrina-goeva
Department and Institution: Molecular Genetics, University of Toronto (Donnelly Centre)
Email Address: aleksandrina.goeva@utoronto.ca
 

Topic Area:
This postdoctoral project aims to apply state-of-the-art machine learning techniques to classify cell types and cell states in the developing human brain at single-cell resolution. Leveraging high-quality, full-length single-cell RNA sequencing data, particularly from human embryonic brain tissue, the project will explore the dynamic molecular landscape underpinning neurodevelopment. The focus will be on distinguishing stable cell identities from transient or context-dependent states, a key challenge in developmental biology and neuroscience.
By expanding HiDDEN, a computational method that refines the case-control labels to accurately reflect the perturbation status of each cell, we aim to disentangle overlapping signals of differentiation, maturation, and circuit connectivity. This approach will go beyond traditional clustering and trajectory inference by integrating splicing variation and other regulatory layers, enabling a more refined understanding of cellular heterogeneity in tissue context.
Importantly, this work has direct implications for understanding the cellular origins of neurodevelopmental disorders such as Autism Spectrum Disorder (ASD). Aberrant differentiation trajectories or altered cell state dynamics may underlie pathological features of ASD. By leveraging datasets obtained as part of BRAIN Initiative Cell Atlas Network (BICAN), we can begin to precisely map these processes in relation to spatial atlas information. Moreover, we can uncover early biomarkers or targets for intervention, with potential to inform future strategies in early diagnosis and child care.
This interdisciplinary project blends computational modeling, developmental neurobiology, and translational relevance, offering a novel framework for interpreting cellular complexity in the human brain. Collaboration across machine learning and experimental biology will be essential to realize the full potential of this work in both scientific discovery and clinical impact.

Lab website: https://lab.research.sickkids.ca/hopyan/
Department and Institution: Developmental and Stem Cell Biology, SickKids | The Hospital for Sick Children
Email Address: sevan.hopyan@sickkids.ca
 

Topic Area:
Morphogenesis is an inherently biophysical process. Emerging proposals link signalling pathways, cellular behaviours, and tissue properties to explain how the embryonic body and organ primordia are shaped. My multidisciplinary lab integrates murine genetics with physical tools to measure and manipulate the determinants of morphogenesis.
For organ primordia such as the limb bud, mandibular arch, and heart, we examine how biophysical gradients of tissue stiffness and membrane potential organise cell movements to shape tissue, and how signalling pathways such as WNT5A-YAP co-regulate those gradients. We are also interested in how
physical forces influence transcription during development. Potential applications of these studies include mechanisms of congenital malformations and accelerating functional organ regeneration.

Lab website: www.laboutalab.com
Department and Institution: Leslie Dan Faculty of Pharmacy and Institute of Biomedical Engineering, Keenan Centre for Biomedical Research
Email Address: hagar.labouta@unityhealth.to
 

Topic Area:
The research program in the Labouta Lab seeks to address the underrepresentation of pregnant individuals in drug delivery research and to advance the field of prenatal nanomedicine. Our work is organized into two interconnected areas of inquiry.
First, we develop and optimize targeted nanoparticles to deliver biomolecules precisely at the maternal-fetal interface and to fetal organs. These nanocarriers are designed to address complications that arise in utero and contribute to long-term adverse health outcomes in offspring.
Second, we develop organ-on-a-chip technologies to create preclinical models that recapitulate key biological barriers and disease states during pregnancy. This includes our dynamic placenta-on-a-chip platforms, which simulate mechanical forces, nutrient transport, and immune interactions across different stages of gestation and under pathological conditions such as preeclampsia and fetal growth restriction. These models allow us to characterize the properties of nanoparticles that are safe and effective for use in pregnancy and to evaluate novel prenatal therapeutics in a controlled, human-relevant context.
Our multidisciplinary approach spans stem cell biology, molecular biology, drug delivery, nanomedicine, microfluidics and biomedical engineering. The overarching goal is to translate fundamental discoveries into actionable, clinically relevant interventions. The lab is embedded in a vibrant translational research environment at the University of Toronto and St. Michael’s Hospital, with active collaborations across national and international academic institutions and industry.

Lab website: https://www.thelyelab.com
Department and Institution: Physiology AND Obstetrics & Gynaecology, Lunenfeld-Tanenbaum Research Institute – Mt. Sinai Hospital
Email Address: lye@lunenfeld.ca
 

Topic Area:
Our research studies focus on the mechanisms underlying preterm birth (PTB) and preeclampsia (PE). To define the role of the placenta in pathogenesis of preeclampsia we have: 1) generated and characterized induced trophoblast stem cells (iTSC) from pluripotent stem cells (iPSC) reprogrammed from human amnion, which support novel studies of pathways underlying PE; 2) characterized immune cell and trophoblast phenotypes that are associated with PE, 3) defined interactions at the maternal-fetal interface (decidua/placenta) that support normal placentation (including decidua vascular remodeling). Current studies seek to 1) identify differences in the transcriptomes of iTSCs from normal and PE pregnancies that may reveal the molecular origins of this disease, 2) determine whether iTSCs from PE pregnancies can remodel decidual spiral arteries, 3) recapitulate the ontogenesis of early placental development through co-culture of iTSCs and IPSCs.
We have identified of a role for maternal immune cells as instigators of myometrial inflammation and labour initiation. We are current exploring the novel concept that direct interactions between uterine myocytes and resident immune cells underlie the initiation of labour. We will define the temporal-spatial mapping of these cellular interactions during term and preterm birth, determine the molecular mechanisms by which immune cell-myocyte interactions induce labour gene expression, as well as test potential therapeutics that block macrophage-induced myocyte activation and preterm birth. We have shown that a broad-spectrum chemokine inhibitor can prevent preterm birth in animal models. We will continue to define the mechanisms by which BSCI acts and move this therapeutic towards clinical studies.

Lab website: https://www.milikulab.ca/
Department and Institution: Nutritional Sciences, University of Toronto (Medical Sciences Building)
Email Address: kozeta.miliku@utoronto.ca
 

Topic Area:
Cardiovascular disease (CVD) is the leading cause of mortality globally. Increasingly, research grounded in the Developmental Origins of Health and Disease (DOHaD) framework demonstrates that the roots of CVD begin early in life, even before conception. While maternal influences have been extensively studied, the role of paternal health and nutrition at the time of conception remains underexplored.
Our research lab focuses on how paternal periconception cardiovascular health and diet contribute to the early-life development of CVD risk factors in children. Using data from the nationally representative, population-based, longitudinal Canadian CHILD Cohort Study, we examine how paternal cardiometabolic conditions and dietary patterns may shape offspring trajectories related to obesity and cardiovascular health. These relationships are investigated through the application of advanced longitudinal statistical modeling, including principal component analysis, latent class trajectory models and mixed-effects regression models, to capture complex, time-dependent patterns in child health development.
We also integrate epigenetic analyses to explore whether epigenetic modifications, e.g. changes in DNA methylation, are the potential underlying mechanism, linking early paternal exposures to long-term offspring health outcomes.
This interdisciplinary research bridges clinical epidemiology, molecular biology, and public health, offering a more comprehensive understanding of how paternal health contributes to chronic disease risk. The findings have direct implications for preventive strategies, potentially shifting public health guidelines to include both parents in early-life interventions aimed at reducing the burden of CVD across generations.

Lab website: https://mitchell.csb.utoronto.ca/
Department and Institution: Cell and Systems Biology, University of Toronto
Email Address: ja.mitchell@utoronto.ca
 

Topic Area:
Discovering the Transcriptional Regulatory Networks that Control the Onset of Preterm Labour: At the end of pregnancy during labour, contractions of the myometrium, a layer of smooth muscle cells in the uterus, generate the force needed to expel the fetus. These contractions are initiated when the expression of specific genes in smooth muscle cells are activated in response to hormonal, mechanical and inflammatory signals. This cell-coordinated contractile response can occur prior to term, causing women to enter labour too early. In these cases preterm labour can result in the delivery of underdeveloped infants at high risk of death or complications later in life.
Currently, there is no effective treatment for preterm labour, and little is known about how gene expression changes during pregnancy and labour are regulated. We study the components involved in activating genes in both term labour and preterm labour to better understand the basis of preterm labour and develop new preterm labour therapies. We use genome-wide chromatin biology and gene expression approaches (ATAC-seq, ChIP-seq, RNA-seq) in human and mouse tissues, and CRISPR genome engineering in human cells and mouse models to reveal the genetic links to preterm labour.
The project will involve learning cutting edge genome-wide techniques and large scale data analysis methods to investigate the role of a novel transcription factor in labour onset. CRISPR deletion and endogenous gene tagging will be used to study this transcription factor as a regulator of gene expression in myometrial cells.

Lab website: https://www.mrsantoslab.org
Department and Institution: Molecular Genetics, Lunenfeld-Tanenbaum Research Institute – Mt. Sinai Hospital
Email Address: mrsantos@lunenfeld.ca

Topic Area:
Our lab is interested in the molecular mechanisms that regulate development of the early mammalian embryo and in pluripotent embryonic stem cells, and how such mechanisms are modulated by environmental inputs. In published work, we used a mouse model to show that maternal vitamin C is required for activity of Tet1 in DNA demethylation in the fetal germline, progression of female germ cells through meiosis, and fertility (Blaschke, Nature 2013; DiTroia, Nature 2019). Building upon this work, we have implemented several other mouse models of environmental stress during pregnancy, in which we are studying both the immediate molecular and developmental impact as well as the long-term consequences, including intergenerationally. Environmental perturbations we are particularly interested include psychological stress, malnutrition, infection and hyper/hypothermia. We are interested on the molecular signal transmission from the stressed mother, its epigenetic encoding in embryos and how this manifests in adult physiology in adults, with potential for intergenerational transmission. We envision that the mammalian embryo is highly attuned to variations in environmental factors and capable of discriminating their nature at the molecular, developmental and physiological levels. We also use human cells, including ESCs, to complement and expand upon some of our findings. As always, we are very open to new ideas and input that trainees bring to the lab.

Lab websites: https://lab.research.sickkids.ca/scott/; https://www.wilsonlab.org/index.html
Department and Institution: Developmental and Stem Cell Biology AND Genetics and Genome Biology, SickKids | The Hospital for Sick Children
Email Address: ian.scott@sickkids.ca; michael.wilson@sickkids.ca
 

Topic Area:
The Scott and Wilson labs at The Hospital for Sick Children are seeking a co-supervised Postdoctoral Fellow to pursue work on conserved non-coding gene regulatory elements that regulate cardiopharyngeal development and disease. We have identified via functional and comparative genomics approaches conserved (zebrafish to human) gene regulatory elements that are active during the earliest stages of cardiac and pharyngeal development. Using the zebrafish model, we have further found elements whose early open chromatin status is dependent on the activity of the pro-cardiac Gata5/6 transcription factors. Initial analysis of these “Gata-sensitive” regions has shown that they are highly active in the cardiac lineage and are further enriched for functional disease-associated variants (as validated in zebrafish transgenic and enhancer mutant models) in a patient cohort with Hypoplastic Left Heart Syndrome (HLHS). Our initial work shows that Gata5/6 play key roles in setting the epigenetic framework that later cardiopharyngeal development works from.
We are continuing this work on a number of fronts, including: 1) examining the role of conserved Gata5/6 target regulatory elements and genes in zebrafish heart development; 2) expanding this work to an analysis of pharyngeal (with a focus on Tbx1) development; and 3) carrying out a comprehensive study of conserved regulatory elements for patient variants associated with congenital heart disease and modeling these in zebrafish as well as other assays (MPRA in cultured hiPSC CMs, mouse models, etc.).We are seeking ambitious individuals with cross-disciplinary interests (developmental biology, bioinformatics, comparative and functional genomics, human disease genetics).

Lab website: https://www.serghides.ca/
Department and Institution: Immunology, Princess Margaret Cancer Research Tower
Email Address: lena.serghides@utoronto.ca
 

Topic Area:
With the overall objective of optimizing antiretroviral therapy for pregnant women with HIV and their infants, the aims of the Serghides Lab are: (1) to identify mechanisms that contribute to adverse birth outcomes in the context of HIV and antiretroviral exposure, as well as identify biomarkers of risk, and interventions to improve outcomes, (2) to understand the effects of in utero exposure to HIV and antiretrovirals on the development of children who are HIV exposed but uninfected and identify
underlying mechanisms, and (3) to develop animal and ex-vivo models to facilitate the study HIV and antiretroviral effects in the context of pregnancy.

Lab website: https://lab.research.sickkids.ca/wong/
Department and Institution: Laboratory Medicine & Pathobiology, SickKids | The Hospital for Sick Children
Email Address: apwong@sickkids.ca
 

Topic Area:
Our lab focuses on advancing the understanding of human fetal lung development and the prenatal origins of congenital lung diseases, with a particular emphasis on cystic fibrosis (CF). Unlike animal models, which only partially replicate human lung development, our work leverages a unique combination of human fetal lung tissue and human induced pluripotent stem cell (iPSC)-derived models to study key developmental processes. We have established a robust fetal lung explant culture system to examine branching morphogenesis and epithelial differentiation. Using this system, we demonstrated that Wnt/β-catenin signaling is crucial for airway development, and its disruption leads to reduced branching and impaired differentiation, especially of ciliated epithelial cells.
In parallel, we are investigating the fetal origins of CF. Although CF is clinically diagnosed postnatally, our studies of CF fetal lung tissue at 15 weeks gestation reveal early histopathological abnormalities, including mucus obstruction and altered cellular composition. Single-cell RNA sequencing further indicates a significant expansion of stromal cells and a reduction in epithelial and endothelial populations, implicating early CFTR dysfunction in shaping lung architecture.
Beyond wet-lab experimentation, we are developing in silico models of the human lung by integrating multi-scale biological data. These computational models, validated through our iPSC-derived and fetal
tissue platforms, aim to simulate developmental and disease processes. Ultimately, our goal is to establish a “digital lung” for applications in regenerative medicine and precision therapies.
Our research also extends to other CF-affected organs, enabling a comprehensive view of how CFTR mutations disrupt human development systemically.