Recherche uO, le dépôt numérique de l'Université d'Ottawa, réunit le matériel de recherche et d'enseignement créé par notre communauté universitaire et nos partenaires. Le savoir de l'Université est ainsi disponible à long terme et en accès libre, ce qui lui procure de la visibilité et facilite sa diffusion.

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    Group 2 Innate Lymphoid Cells in Ovarian Health and Disease
    (Université d'Ottawa / University of Ottawa, 2026-07-22) Asif, Sara; Ardolino, Michele; Vanderhyden, Barbara C.
    Group 2 innate lymphoid cells (ILC2s) are a subset of tissue-resident lymphocytes that function as first responders to physiological tissue inflammation, and during malignant transformation, can direct tumor immunity in its early stages. How ILC2s contribute to ovarian health and whether they can be harnessed to improve anti-tumor therapy has not yet been elucidated. Herein, we identified the novel presence of ILC2s in the mouse ovary, and found that they represent a dynamic population that is regulated by hormonal signalling and epithelial-derived cytokines. Our data provides a phenotypic and functional characterization of ILC2s in the ovary during normal reproductive cycling, ovulation, and in a mouse model of polycystic ovarian syndrome. Having identified ILC2s in the healthy cycling mouse ovary, we next sought to extend our studies to ovarian cancer, where the role of ILC2s is undefined. Herein, we report that IL-33 treatment increases ILC2 abundance, activation, and effector function in mouse ovarian tumors. IL-33-activated ILC2s upregulate surface expression of PD-1, providing a rationale to consider anti-PD-1 (αPD-1) immunotherapy in combination. Indeed, we found that IL-33+αPD-1 treatment significantly improves survival in mice bearing ovarian tumors compared to either monotherapy. IL-33 treatment enriches ILC2s in the tumor microenvironment where they exhibit enhanced cytotoxic capabilities and expression of effector molecules IL-5 and IL-13. Survival analyses revealed that IL-5, but not IL-13 is dispensable for the therapeutic efficacy of IL-33+αPD-1 treatment. Beyond ILC2s, T cells, B cells, and NK cells all contribute to the therapeutic effect of IL-33+αPD-1 unveiling a model in which this combination treatment exerts its effects through multiple immune pathways. Together these data position ILC2s as key mediators of ovarian homeostasis and disease.
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    Unlocking the Potential of Automated Placental Screening to Predict Cardiovascular Risk After Pregnancy Complications
    (Université d'Ottawa / University of Ottawa, 2026-07-21) Zeidan, Dalia; Bainbridge, Shannon A.
    Introduction: Placenta-mediated diseases (PMDs) are critical sex-specific indicators of future maternal cardiovascular disease (CVD) risk. Placental maternal vascular malperfusion (MVM) may provide insight into postpartum CVD risk, but standard pathology assessment is time-consuming, resource-intensive, and dependent on specialized expertise. Objective: This study aimed to investigate whether placental MVM, assessed either by manual pathology review or automated image analysis, could help identify women at elevated lifetime CVD risk at six months postpartum following a pregnancy complicated by a PMD. Methods: In a multi-site cohort of women with PMDs (n=280), placental whole-slide images were reviewed by a perinatal pathologist, and lifetime CVD risk was calculated using postpartum clinical and biochemical cardiovascular risk factors. An attention-based deep learning model was applied to a subset of placental images (n=208) for automated MVM detection. Results: Manually assessed MVM and algorithm-derived MVM were not significantly associated with high lifetime CVD risk (AUC=0.52) and provided no incremental predictive value beyond clinical factors. The automated model demonstrated weak-to-modest performance for MVM detection due to lesion complexity and gestational context. Conclusion: Neither manual nor automated MVM assessment currently provides sufficient accuracy for use as a standalone CVD triage tool. Future progress requires integrated, multimodal approaches combining placental pathology with clinical and biochemical measures to improve postpartum risk stratification.
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    A Screen for Novel Regulators of Polyphosphate Accumulation in Escherichia Coli Identifies Genes Involved in Envelope Stress, Central Metabolism, and Phosphate Homeostasis
    (Université d'Ottawa | University of Ottawa, 2026-07-21) Simms, Abby; Downey, Michael
    Polyphosphates (polyP) are chains of inorganic phosphate that are present in a wide variety of organisms such as yeast, mammals, and bacteria. Despite the interesting and diverse functions of polyP across systems, bacterial polyP is of particular interest to researchers due to its contributions to bacterial survival. Across bacterial taxa, polyP accumulation promotes resistance to diverse environmental stressors, can act as a protein chaperone, and positively regulates pathogenicity, making polyP an interesting target to help treat bacterial infections. In the gram-negative bacterium, Escherichia coli, polyP is synthesized from ATP by a single polyphosphate kinase (PPK) enzyme, and is degraded into inorganic phosphate by an exopolyphosphatase. PolyP synthesis by PPK in E. coli is stress-dependent, as there is little to no detectable polyP present in the absence of stress, followed by the rapid accumulation of polyP upon exposure to stressors such as nutrient limitation. Despite this stress-specific activity, the exact trigger(s) of PPK activity at the onset of stress remain uncharacterized, as PPK’s expression and in vitro activity do not correlate with polyP accumulation. To address this open question, this work aims to characterize novel regulators of polyP that can be leveraged to investigate the mechanism of PPK activation. To achieve this, we conducted a screen of single-gene deletion mutants targeting a highly conserved family of signalling proteins called two-component systems (TCS), which have existing links to polyP biology. In doing so we highlighted five polyP-regulators, three of which (cpxA, arcB, and arcA) have not yet been reported in the literature. Upon following up on one of our hits, the envelope stress-sensing histidine kinase CpxA, we found that activation of the CpxRA TCS promotes an increase in polyP accumulation. However, polyP regulation by this system appears to be independent of PPK or PPX expression, leaving the door open to future analyses of PPK regulation, possibly at the level of localization or oligomerization. Overall, this work contributes to our fundamental knowledge surrounding the relationship between PPK activity, polyP accumulation, and cellular stress.
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    Point-of-Care Ultrasound Assessment of Left Ventricular Function in Rapid Atrial Fibrillation or Flutter Patients in the Emergency Department
    (Université d'Ottawa | University of Ottawa, 2026-07-21) Giannakakis, Sophia-Maria; Perry, Jeffrey J.; Stiell, Ian
    Objective: The aim of this thesis is to evaluate the utilization of point-of-care ultrasound (POCUS) for left ventricular function (LVF) assessment by emergency physicians for the diagnosis and management of heart failure in rapid atrial fibrillation or flutter. Methods: A national survey of emergency physicians explored the integration and perceived barriers related to POCUS use in rapid atrial fibrillation or flutter. Subsequently, a health records review at The Ottawa Hospital ED studied diagnostic agreement of POCUS LVF assessment between ED physicians, cardiologists, and ED POCUS expert. Secondary outcomes were also analyzed regarding rapid atrial fibrillation or flutter management. Results: A fair level of agreement between cardiologists and ED physicians (k= 0.34 CI 95% 0.10-0.58) and moderate agreement was found between cardiologists and ED POCUS expert physician (kappa = 0.63 (CI 95% 0.43-0.82). A higher proportion of rapid atrial fibrillation/flutter patients with ED-performed POCUS were admitted to hospital (40% vs 19%, p<0.0001) and rate controlled with beta blocker (38% vs 24%, p=0.009) or digoxin (14% vs 5%, p=0.007). Conclusion: The utilization of POCUS in the rapid atrial fibrillation/flutter patients can help guide diagnosis and management of heart failure in the ED.
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    Quantitative MRI as a Biomarker of Disease Severity in Neuromuscular Disease
    (Université d'Ottawa | University of Ottawa, 2026-07-21) Satarkar, Tanay; Warman Chardon, Jodi
    Introduction: Oculopharyngeal muscular dystrophy (OPMD) is a slowly progressive disorder marked by ptosis, dysphagia, and proximal muscle weakness. Reliable biomarkers for monitoring are limited, making progression difficult to track in clinics and future trials. Quantitative MRI (qMRI), particularly fat-fraction (FF) and water measures offer a non-invasive way to assess muscle involvement and follow change over time. Aim: To evaluate 97 muscles in OPMD using qMRI and determine if diffusion-related MRI markers [apparent diffusion coefficient (ADC) intravoxel incoherent motion (IVIM)], and T2 relaxation time identify earlier signs of disease activity compared to muscle FF. Methods: The study included 52 participants, 40 patients with OPMD and 12 controls with whole body 3T qMRI. For FF and ADC, 97 muscles were segmented and 24 thigh muscles were segmented for IVIM and T2 map using ITK SNAP version 3.8.0. Statistical analyses used GraphPad Prism and R-studio using, Wilcoxon unpaired tests and Spearman correlation p <0.05. Results: Muscles such as adductor magnus (41.2±28.9 %), soleus (39.2±25.9 %), and biceps femoris long head (BL) (33.8±25.2 %), showed higher FF. Higher FF was linked to a stronger negative correlation between FF-ADC, adductor magnus (spearman’s ρ = -0.90), soleus (spearman’s ρ =-0.83), biceps femoris long head (spearman’s ρ = -0.87)), and FF-IVIM true diffusion (spearman’s ρ =-0.89 CI, -0.94, -0.80 respectively). IVIM perfusion-fraction correlated positively with FF in adductor magnus and biceps femoris long head (spearman’s ρ = 0.80) in the early disease duration period (0-5 years). Exploratory disease-duration stratification showed ADC did not rise prior to fat replacement, as might occur with inflammation and edema; instead, ADC decreased as fat replacement increased. Discussion: FF is a sensitive marker of disease severity and shows a strong negative correlation with diffusivity markers. In this cross-sectional analysis, diffusion values do not rise before fat replacement onset. Identifying sensitive biomarkers of OPMD severity and disease progression is important to identify treatment windows for future trials.