UVicSpace | Institutional Repository
UVicSpace is the University of Victoria’s open access scholarship and learning repository. It preserves and provides access to the digital scholarly works of UVic faculty, students, staff, and partners. Items in UVicSpace are organized into collections, each belonging to a community.
For more information about depositing items, see the Submission Guidelines.
Recent Submissions
Exploring the challenges and opportunities when public policy does not meet the needs of Indigenous communities in Canada
(2026-06-16) Lewis, Diana
Having worked in government policy for most of her career, Dr. Lewis will revisit historical examples of public policy that failed to meet the needs of Indigenous communities. Have things changed? Sadly, in many cases, they have not.
Drawing on case studies from across Canada, Dr. Lewis will examine how public policy continues to miss the mark and the consequences this can have for Indigenous communities. In an environment where major projects are increasingly being fast-tracked in the name of national unity and economic security, these policy gaps can place Indigenous communities at greater risk.
Physical activity mHealth tailored to postpartum individuals with lumbopelvic pain
(2026) Hollman, Heather; Rhodes, Ryan E.
Background: Postpartum moderate-to-vigorous intensity physical activity (MVPA) is essential for the health of the birth parent, their future pregnancies, and their children. Unfortunately, over 55% of postpartum individuals are not meeting recommended MVPA guidelines and face significant barriers to MVPA participation such as lack of childcare, sleep, and time. Up to 67% of postpartum individuals suffer from lumbopelvic pain (LPP) which can affect their ability to be active. Mobile health applications (mHealth apps) have great potential for promoting MVPA amongst postpartum individuals; however, those currently available lack quality and evidence-based recommendations and have limited effectiveness and engagement.
Objectives: To design and develop an evidence-based, acceptable, usable, feasible, scalable, and low-cost MVPA promotion mHealth app tailored to postpartum individuals with LPP. A series of three studies, following the IDEAS (Integrate, Design, Assess, and Share) framework, were conducted to meet this overarching objective.
Methods: This proposal consists of six chapters. Chapter 1 provides an introduction with a brief overview of the background literature and dissertation objectives. Chapter 2 provides a more thorough background literature review. Chapter 3 is a systematic review of mediators of postpartum PA behaviour change interventions. Chapter 4 is a cross-sectional study to determine predictors of MVPA intention-PA translation among postpartum individuals. Chapter 5 is a co-design study, in partnership with key knowledge users (i.e., individuals with lived expertise of postpartum LPP and healthcare providers) to tailor a previously existing theory-informed and evidence-based MVPA promotion mHealth app to postpartum individuals with LPP. Chapter 6 is a general discussion to synthesize the findings of the aforementioned three studies and make suggestions for future directions.
Significance: The findings of this research program illuminates the unique barriers, needs, and considerations for MVPA and mHealth when intervening with postpartum individuals with LPP. They also inform future large scale trials with the ultimate intents of optimizing health and reducing chronic disease for postpartum individuals themselves, their future pregnancies, and their children.
A factor analytic investigation of allostatic load and associations with cognitive performance
(2026) McDowell, Cynthia; MacDonald, Stuart Warren Swain
Introduction: Allostatic load (AL) reflects the cumulative physiological burden resulting from long-term chronic stress and has been linked to a range of adverse health outcomes, including cognitive impairment. However, operationalizing and measuring AL – requiring the integration of heterogeneous biomarkers across distinct physiological systems into a single unified construct – remains a significant methodological challenge. Research applying latent factor modeling to examine the underlying structure of AL is particularly limited, especially in older adults, despite AL being conceptualized as a cumulative, multisystem, and protracted process.
Objectives: The present dissertation addressed two primary research questions: (1) Which latent factor structure best indexes AL in older adulthood? and (2) Is this AL latent factor model associated with individual differences in cognitive performance? Methods: Seventeen biomarkers spanning four physiological systems (cardiovascular, anthropometric, metabolic, and inflammatory) were analyzed in a large sample (N = 12,646) of community-dwelling adults aged 65 and older (Mage = 73.10 years; 50.13% Males). Four distinct AL measurement models were tested and compared using confirmatory factor analysis to identify the model of best fit for males and females separately. Structural equation modeling was then used to examine whether the final latent AL factor was associated with six cognitive tasks spanning executive functioning, memory, and psychomotor processing speed domains, while adjusting for age, education, and total medication use.
Results: A bifactor model with relaxed orthogonality constraints emerged as the best-fitting structure for both sexes, whereby biomarkers loaded onto both a general AL factor and system-specific latent factors. In males, tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6) were the strongest contributors to the general AL factor, highlighting the central role of inflammatory processes in males. In females, triglycerides and high-density lipoprotein (HDL) cholesterol were the strongest indicators of AL, suggesting that lipid dysregulation may be more salient in the expression of AL among aging females. Using this bifactor model structure, the general AL factor was significantly associated with individual differences in performance across all three cognitive domains in both sexes, even after adjusting for covariates.
Conclusion: This dissertation provides an empirically rigorous and theory-informed modeling approach that advances both the conceptual and methodological foundations of AL research. The findings highlight the value of a latent AL factor for capturing individual differences in cognitive health and provide key insights for measuring multisystem dysregulation, understanding sex-specific biological differences, and enhancing early identification of cognitive vulnerabilities linked to chronic stress in older adults.
Rewiring co-stimulatory receptors with targeted antibody agonists to improve cell therapy against cancer
(2026) Goodwin, Sydney; Nelson, Brad H.; Smazynski, Julian
Adoptive cell therapies (ACTs) have transformed cancer treatment, yet their efficacy is often limited by poor T cell persistence and sustained functionality. Effective anti-tumour immunity requires durable co-stimulatory signalling, particularly through pathways such as CD28, while inhibitory checkpoint pathways including PD-1 and CTLA-4 suppress T cell activity within the tumour microenvironment. Although immune checkpoint inhibitors (ICIs) can relieve inhibitory signalling, they remain dependent on pre-existing anti-tumour immunity. One potential approach involves the use of agonistic antibodies to stimulate co-stimulatory receptors on T cells; however, systemic administration of co-stimulatory agonists is associated with significant toxicity due to indiscriminate activation of endogenous immune populations. Another attractive approach is the use of switch receptors that combine the extracellular domain of a checkpoint protein with the intracellular domain of a co-stimulatory protein, such that endogenous ligand binding delivers a targeted stimulatory signal to adoptively transferred T cells. However, switch receptors are limited by endogenous ligand expression that varies between patients and cancer types, reducing their versatility and predicted efficacy.
To address these limitations, we hypothesized that clinically approved ICIs could be repurposed as selective activators of chimeric co-stimulatory receptors (CCRs), enabling antibody-mediated enhancement of adoptively transferred T cells while avoiding broad systemic immune activation.
To test this hypothesis, we engineered multiple CCR constructs fusing the extracellular domains of immune checkpoint proteins (PD-1, PD-L1, and CTLA-4) with the intracellular domain of CD28. Human T cells expressing these CCRs were evaluated for functional activation following stimulation by clinically relevant ICIs. In vitro, CCR-expressing T cells demonstrated robust activation in response to checkpoint antibodies, including enhanced IL-2 secretion, proliferation, and cytotoxicity that exceeded responses induced by conventional CD28 agonist antibodies. These findings established that ICIs can be functionally repurposed to deliver potent co-stimulatory signals through our engineered receptors.
However, despite strong in vitro activity, in vivo adoptive transfer studies in NSG mouse models revealed a profound and unexpected loss of CCR-expressing T cells following systemic ICI administration. This depletion occurred across multiple CCR constructs and antibody subclasses, suggesting that antibody engagement may trigger deleterious immune-mediated mechanisms that override the intended co-stimulatory effects. Mechanistic studies investigating antibody Fc interactions demonstrated that Fc engineering strategies altered these effects in vitro but did not restore CCR+ T cell persistence in vivo. These findings implicate complex contributions from Fcγ receptor interactions, complement activation, and/or other immune processes.
Collectively, this work establishes checkpoint-converting CCRs as a novel and conceptually compelling platform to improve cellular immunotherapies, while also identifying a major translational barrier to their implementation. More broadly, this thesis highlights the importance of Fc biology, host immune interactions, and preclinical model selection in the development of antibody and cell-based combination strategies. Although substantial mechanistic challenges remain, resolving the pathways responsible for CCR+ T cell depletion may enable the future development of next-generation ACT platforms that leverage existing clinically approved immunotherapies to enhance anti-tumour responses.
2025 Gladys Nipp and Stephen Mah Award-Winning Research Proposal
(University of Victoria Libraries, 2025) Chau, (Ngoc Tram) Anh
In this award-winning 500-word research proposal, graduate student (Ngoc Tram) Anh Chau describes a proposed use of UVic Libraries' Chinese-Canadian collections.