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Pharmacokinetics and efficacy of a tunable curcumin-loaded polymeric nanoparticle for neonatal neuroprotection
Thesis (Ph.D.)--University of Washington, 2025Newborns with neurological disorders are in particular need of therapeutic intervention, due to theimmaturity and rapid brain development in the perinatal period, which can increase risk of long-term
neurodevelopmental disability. In many neurological disorders, including neonatal or perinatal brain
injury, inflammation results in sustained activation of pro-inflammatory microglia that drives ongoing
pathology and worse outcomes. This thesis research focused on using anti-inflammatory small molecules-
loaded polymeric nanoparticles as potential neuroprotective agents for neonatal or perinatal brain disease
and injury. Firstly, we quantified the pharmacokinetics (PK) and biodistribution of polymeric
nanoparticles formulated using different surfactants as stabilizers, and investigated the effects of
surfactants on PK profiles and biodistribution of polymeric nanoparticles in the term-equivalent rat. Our
results show that the PK and biodistribution of polymeric nanoparticles can be adjusted by changing the
surfactant. To increase the systemic half-life of polymeric nanoparticles and formulate nanoparticles with
improved bioavailability, Pluronic F127 (F127) should be used as the stabilizer. Next, using F127 as the
stabilizer, we investigated the effects of PLGA length, stabilizer concentration, polymer functionalization,
and formulation method on curcumin loading. Upon successful optimization of a PLGA-PEG
nanoparticle with high curcumin encapsulation efficiency and drug loading, we assessed particle PK and
biodistribution in term pigs. To move into a clinical-trial ready model, we also assessed particle
accumulation in the fetal growth restricted (FGR) piglet brain following different administration routes.
We found curcumin-loaded nanoparticles were colocalized with microglia after intranasal administration,
which demonstrated the potential of our polymeric nano-platform to be used as a microglia-targeting
vehicle for hydrophobic molecules in perinatal brain injury. Finally, we used the curcumin-loaded
nanoparticles with optimized curcumin loading and systemic circulation half-life to evaluate the
neuroprotective effects in neonatal rats with brain injury at different developmental ages. The relationship
between developmental age and neuroprotective effect of the nano-therapy was revealed: after a single
dose of curcumin-loaded nanoparticles, neuroprotective effects were only observed in the acute period in
late preterm-equivalent rats with hypoxic-ischemic (HI) brain injury, but not in term-equivalent or late-
term equivalent rats with HI. Our results suggest that 1) neonatal dose determination should be based on
developmental age, and 2) multiple doses of curcumin-loaded polymeric nanoparticles are needed for
neonatal neuroprotection after HI
Paying it Forward: An Exploration of Mentor Experiences Among Women Sheet Metal Workers
Thesis (Master's)--University of Washington, 2025Tradeswomen are underrepresented in the construction industry and face gendered occupational risk factors that impact mental and physical health. Mentorship is a tradeswomen-identified strategy to support the retention and wellbeing of incoming workers to cope with negative gendered experiences. We conducted a five-year randomized control trial to evaluate the efficacy of a mentorship program for women sheet metal workers, which included an online mentorship training for mentors. Here, we explore the experience of mentors in the program, including their reflections about how the mentorship training and program impacted them, their mentees, and their communities. Ten interviews were conducted and thematically analyzed using deductive codes informed by Social Cognitive Theory (SCT) and inductive codes that emerged from the data. Mentors described their motivation to support mentees through the lens of their gendered experience in the field and reported understanding and using skills from the training with their mentees and in their own lives, including the development of communication skills and increased confidence. They expressed motivation to engage in tradeswomen-supportive programming at the local level because of participating in the program. Mentors also reported significant barriers to mentorship, including lack of time, lack of responsiveness from mentees, and cultural norms in the trades. These findings provide insight and context into the dimensions of the mentor role in an occupational-health focused intervention. These results inform recommendations for future tradeswomen-supportive programming; they also shed light on the role of individuals as intermediaries in supporting health promoting behavior
The Analysis of Photochemical Nitrile Imine Cross-Linking for Ribonucleosides in Gas-Phase Ions
Thesis (Master's)--University of Washington, 2025This research presents the exploration of nitrile imine cross-linking related to ribonucleoside ions in the gas phase. Riboguanosine was tagged with 4-(2-phenyl-2H-tetrazol-5-yl)benzoic acid at the 5’O-ribose position. The tagged nucleosides were analyzed by liquid chromatography mass spectrometry (LC-MS) and tandem mass spectrometry including ultraviolet photodissociation tandem mass spectrometry (UVPD-MS) and collision-induced dissociation tandem mass spectrometry (CID-MS). Crosslinking was found to occur in tetrazole-guanosine ions upon N2 loss under CID-MS2 and UVPD-MS2. The spectra from CID-MS3 and UVPD-CID-MS3 also suggested that the cross-linking involved interactions between the guanine carbonyl group and the nitrile imine
From River to Root: Native Traditional Food Plants, Salmon, and the Work of Living Sovereignty – Restoring Salmon Habitat & Revitalizing Traditional Foodways Through Tribal Leadership
Thesis (Master's)--University of Washington, 2025This management plan preface aims to introduce a community-guided management plan for a traditional food forest and salmon habitat restoration site at Chief Leschi Schools (CLS) in Puyallup, Washington. Developed in partnership with educators, students, and project partners, the management plan centers place-based, community-led action in response to intersecting environmental and social crises. Specifically focusing on, the ongoing impacts of settler colonial land management and societal structures, the systematic dismantling of traditional food systems, and the urgent need for climate adaptation strategies (Gilio-Whitaker, 2019; Coté, 2022). This project approaches restoration as a relational, action-based process rooted in centering Tribal sovereignty and leadership while also critically engaging with and seeking to disrupt ongoing settler-colonial discourses and impacts that are deeply intertwined and embedded in environmental spaces. This aligns with growing efforts to build co-management frameworks that uphold Indigenous knowledge systems and Indigenous community-defined priorities, demonstrating how meaningful partnerships can support both ecological recovery and cultural revitalization when tribal leadership is respected and prioritized in habitat restoration (Donatuto et. al., 2014; Dent et. al., 2023)
Light-Regulated Reproduction of Ctenophores
1. Light-regulated spawning in Ctenophore
Light is one of the most common environmental factors affecting animal behaviors and life cycles. Ctenophora, as one of the earliest branched lineages among metazoans1, can provide insight on how light-regulated behaviors have evolved in animals. Mnemiopsis leidyi, an Atlantic coast ctenophore, requires 3-4 hours of darkness to spawn2. Bolinopsis microptera and Pleurobrachia bachei suggest they need to be exposed under bright light. This requirement is opposite of M.leidyi, despite B.infudibulum is phylogenetically closely related to M.leidyi. However, there is no experiment that clearly determines whether the spawning happens in a dark environment or light environment3. Furthermore, it is not clear whether it’s the dark to light transition or only the light cue triggers the spawning. I hypothesize that strong light triggers spawning in Bolinopsis, Pleurobrachia, and another species Beroe abyssicola regardless of day-night cycle.
I conducted preliminary experiments on B.microptera and P.bachei. They were collected after sunset (B.microptera n = 9, N = 18, P.bachei n = 5, N= 10) and before sunset (B.microptera n = 4, N = 8, P.bachei n = 4, N= 8). The number of animals in each group changes due to availability at the FHL dock.The experiment group was exposed to headlight for 12 hours, and the control group was kept under cover of tin foil in darkness for 12 hours. There is no B.abyssicola around the dock now, so all the animals used (n=2, N=4) come from kreisel maintained by Dr. Eric Edsinger. Each group was put under light for 2 hours. The results show that all B.microptera and P.bachei collected after sunset spawned under light and did not spawn in dark. B.microptera and P.bachei collected after sunset spawned in both groups. No Beroe spawned. The results indicate that light activation of spawning seems to not be associated with phylogenetic relationship, and gradual transition from light to dark is needed for dark inhibition of spawning.
2.Ctenophore imaging methods
I developed a protocol to stain ctenophores for microCT scanning collaborating with Dr.Rebecca Varney and Jorge Merchán. The Pleurobrachia bachei was fixed in Rain X for one hour at room temperature 4. 1.5% lugol iodine solution was added to the sample for contrast staining. From the microCT scan results, shrinkage in size has been observed, but the morphology, including internal structure remains intact
Designing for and Exploring Justice-Oriented Citizenship in Adult ESOL Education
Thesis (Ph.D.)--University of Washington, 2025Immigrant and refugee newcomers to the U.S. face the daunting task of navigating cultural, economic, and civic integration (Wrigley, 2012)--often without the support of federal or even local governments. Those that find their way to adult education programs such as English for Speakers of Other Languages (ESOL) courses, experience a strong emphasis on workforce education as mandated by the Workforce Innovation and Opportunity Act (WIOA) which funds much of adult basic education. Programs that attempt to emphasize civics often provide a shallow, individualistic approach to democratic engagement that primarily focuses on basic access to public services, naturalization and voting, and volunteerism. While this can be beneficial knowledge, it does not on its own prepare newcomers to fully engage in U.S. democracy. This three paper dissertation explores how one ESOL-civics program for adult learners adopted a justice-oriented approach to civics and the impacts of this approach on learning as a form of belonging and becoming. The first paper offers an empirical analysis utilizing qualitative, community-based design research methods to examine justice-oriented citizenship practices in the ESOL context, interweaving students’ participation patterns and identity shifts as evidence of their learning. The second paper is written for practitioners and provides concrete, on-the-ground approaches to implementing justice-oriented civics in adult ESOL classrooms while simultaneously considering the challenges for federally funded programs. Lastly, in the spirit of reciprocity, the third piece is written for the organization where this research was conducted. As a program update and report, the third piece addresses concerns and lines of inquiry co-developed with program staff
Differential Disclosure Experiences Amongst Sexual Victimization Survivors: Exploration of Alcohol Use, Sexual Risk Behaviors, and Mental Health Outcomes
Thesis (Master's)--University of Washington, 2025Sexual victimization is a pervasive issue that significantly impacts the physical, mental, and emotional well-being of survivors. This study investigates how disclosure experience differences influence variability in negative post-victimization outcomes - specifically alcohol use, sexual risk behaviors, and mental health symptoms- amongst cisgender women survivors of sexual victimization (N=347), aged 21-30. Through secondary data analysis, we assessed disclosure characteristics, including disclosure status (completed or non-disclosure), recipient type (informal vs. formal), and perceived helpfulness across assault types - and their relationship to post-victimization negative outcomes. Findings reveal that, contrary to prior literature, survivors who do not disclose their victimization exhibited lower levels of sexual risk-taking in comparison to survivors who did disclose their victimization. Notably, when examining only the type of disclosure recipient, survivors of adult/adolescent sexual assault (ASA) who disclosed exclusively to formal recipients (e.g., medical professionals, law enforcement) exhibited significantly higher mental health symptoms, compared to those who experienced other assault types or disclosed to different recipient types. However, when factoring in perceived helpfulness of their disclosure, survivors from all assault types who felt their disclosure was helpful reported significantly lower alcohol use and risk, particularly when disclosing exclusively to formal recipients. These findings highlight the nuanced impact of disclosure on recovery experiences and underscore the need for improved support mechanisms for survivors. Insights gained are essential for future research and tailored interventions targeting victimization populations
Quantitative Pipelines for Tracking and Understanding the Evolution of Cerebrovascular Atherosclerosis with Multi-contrast, Multi-time Point Vessel Wall Magnetic Resonance Imaging
Thesis (Ph.D.)--University of Washington, 2025Given the substantial global health burden and anticipated rise in mortality rates associated with stroke, imaging of cerebrovascular atherosclerotic plaque plays a crucial role in stroke prevention efforts. Three-dimensional (3D), multi-contrast MR vessel wall imaging (VWI), applied to both carotid and intracranial arteries, offer non-invasive and comprehensive techniques to directly visualize atheromatous plaques and discern their composition, including features such as Gadolinium contrast enhancement (CE) and intraplaque hemorrhage (IPH). Particularly in longitudinal studies, this capability allows for the monitoring of lesion evolution over time, providing valuable insights into the disease process and the efficacy of medical interventions. This research presented advances in VWI analysis of both carotid and cerebral atherosclerosis and deepens our understanding of the evolution of atherosclerosis in the context of stroke.Firstly, regarding intracranial atherosclerosis, standardized pipelines for 3D multi-planar, multi-contrast, and multi-time point imaging review were established, ensuring reproducibility in measuring plaque morphology. A novel CE map was introduced to objectively quantify plaque CE intake. In one of the first prospective studies tracking intracranial atherosclerosis evolution using 3D VWI, this research observed the evolution of intracranial plaques over a 1-year follow-up period and found that plaques progressing over time demonstrated inward remodeling and lumen loss, while regressing plaques exhibited luminal expansion. Significantly, plaque CE and diabetes mellitus were identified as biomarkers predicting plaque progression.
Secondly, tailored analysis pipelines were proposed for two complementary carotid VWI contrasts, enabling consistent measurements of vessel thickness, plaque burden, and IPH. Through a long-term prospective study spanning up to 6 years with up to 5 scans per patient, our research revealed the systemic nature of atherosclerosis, characterized by bilateral plaque evolution symmetry. IPH emerged as a significant driver of plaque progression, capable of disrupting bilateral symmetry and accelerating plaque burden increase. These findings underscore the critical importance of integrating IPH assessment into clinical evaluations of plaque progression.
Collectively, these studies establish robust quantitative methods for analyzing vessel wall imaging and provide critical insights into atherosclerotic disease progression in cerebrovascular territories. By establishing the clinical significance of imaging biomarkers like contrast enhancement and intraplaque hemorrhage, this research enables improved risk stratification and monitoring of treatment response, potentially advancing stroke prevention strategies
COVID-19 and Influenza Vaccine Acceptance and Hesitancy Among Caregivers of Children with Cancer
Thesis (Master's)--University of Washington, 2025Introduction:Children with cancer are immunocompromised and at increased risk for complications from infections including COVID-19 and influenza. Vaccination is recommended, but caregiver perceptions in this high-risk group are not well understood.
Methods:
We conducted a cross-sectional survey of English- and Spanish-speaking caregivers of pediatric oncology patients at a large urban pediatric hospital from March to June 2022. The survey addressed COVID-19 and influenza vaccine knowledge, attitudes, and experiences and included validated questions to identify vaccine hesitancy. Caregiver survey responses were linked to their child’s electronic health record data. COVID-19 vaccine acceptance, defined as documented or caregiver-reported vaccine receipt or intention to vaccinate if age-ineligible at survey administration, was the primary outcome. Influenza vaccine acceptance was a secondary outcome. Associations between survey responses and COVID-19 or influenza vaccine acceptance were assessed using multivariable logistic regression.
Results:
Of 441 eligible caregivers, 100 (23%) responded. COVID-19 vaccine acceptance was 71%, influenza vaccine acceptance was 82%, and 57% of caregivers were identified as vaccine hesitant. Vaccine hesitancy was significantly negatively associated with COVID-19 vaccine acceptance. Perceived vaccine safety, efficacy, prior influenza vaccination, and pandemic-related concern about cancer were positively associated with COVID-19 vaccine acceptance.
Conclusion:
Caregiver perceptions strongly influenced COVID-19 and influenza vaccine acceptance. Specific and provider-driven communication strategies are needed to address ongoing vaccine hesitancy in this uniquely at-risk population
Physical Accessibility Guide for LeMay - America's Car Museum
Thesis (Master's)--University of Washington, 2025Disabled people are just as worthy of access to information as any other group of people, including at museums. And for museums, fulfilling their mission should mean ensuring genuine opportunities for engagement for visitors of all abilities. LeMay - America's Car Museum (ACM) attracts local and national visitors and seeks to understand how it can improve physical access to its exhibits and galleries for current and future visitors. The purpose of this project was to create an implementation guide that aids the museum in their journey towards accessibility. This guide delineates the access issues and solutions specific to ACM and provides information, resources, and background. In this project, accessibility is focused on the following physical disabilities: limited mobility, visual impairment, and auditory impairment. The use of existing literature and best practices on accessibility within the museum field helped to inform the initial approach. Importantly, the implementation of a focus group composed of individuals with physical disabilities was critical and highlights the importance of including disabled people in any process that is related to them. Since making museum-wide changes can be a lengthy and expensive process, this guide takes a phased approach to implementing these changes, organizing them into categories and then breaking those categories down further into what are “low-hanging fruit” or more lengthy processes. The audience for the guide are staff at ACM who will implement the change. Ultimately, the outcomes are for visitors with disabilities to feel engaged in a space that is designed for universal access