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Multiplex Methods for Profiling and Programming Protein Degradation
Get PDFThesis (Ph.D.)--University of Washington, 2025This thesis focuses on the development of multiplex experimental methods for profiling and programming intracellular protein degradation. In addition, it explores the synergistic application of deep-learning models for understanding and engineering protein function at scale.Chapter 1 provides an overview of the mechanisms governing proteome homeostasis and outlines the technological gap that has historically limited our ability to study these systems. I review how the convergence of multiplex cellular assays and deep learning models offers a new paradigm for dissecting endogenous regulatory networks and engineering novel protein functions.
Chapter 2 presents COMET (COmbinatorial Mapping of E3 Targets), a pooled assay for mapping E3 ubiquitin ligases to their substrates. By coupling combinatorial libraries of dual-fluorescent reporters with E3-targeting CRISPR guides, we enabled the many-by-many measurement of E3-dependent changes in protein abundance within a single experiment. I apply COMET to identify substrates of SCF complex E3 ubiquitin ligases as well as map the E3s mediating degradation of short-lived transcription factors, revealing that proteolytic regulation is often characterized by complex, many-to-many connectivity rather than simple one-to-one relationships. Finally, I demonstrate the use of deep-learning-based structural prediction models for the in silico validation of COMET-nominated E3–substrate pairs, pointing toward a future where computational nomination guides experimental validation.
Chapter 3 shifts from mapping endogenous degradation to programming it. Here, we demonstrate a multiplex framework for the discovery of functional de novo designed “proximity handles.” We designed a library of binders targeting various effector proteins and characterized them using LABEL-seq, a multiplex RNA-barcoded protein abundance assay. This approach identified hundreds of designs capable of mediating the stabilization or degradation of a target protein. We further validated a subset of designs in orthogonal assays, demonstrated handle-mediated degradation of the endogenous oncoprotein MCL1, and applied these handles to remodel mitochondrial organization. This study establishes a generalizable pipeline linking computational protein design to high-throughput cell-based readouts.
To conclude, Chapter 4 discusses future directions at the interface of multiplex technology and deep learning, specifically focusing on the potential for closed-loop design-build-test-learn cycles and the expansion of these methods to enzyme engineering
All my friends are doing it: Perceived social norms predict heavier sports betting behavior among young adults
No full textBackground. Sports betting is the fastest growing gambling behavior, particularly among young adults. Despite burgeoning evidence of the public health concerns associated with sports betting, antecedents of this addictive behavior are largely understudied. Informed by seminal psychological theories of conformity and existing norms-based prevention paradigms for high-risk behavior, the current study aimed to examine perceived social norms as a potential explanatory factor for sports betting behavior. Method. The sample was comprised of 221 young adults from 36 different US states (Mage=24.4; 77.7% male; 64.6% white). Eligibility criteria included betting on sports at least twice in the past month. At baseline, participants reported perceptions of friends’ approval and engagement in sports betting, and then two weeks later reported indices of their own sports betting behavior. Results. Generally, young adults perceived their peers to wager much more on sports betting than they themselves reported wagering, suggesting potential normative misperceptions. Those who perceived their friends to be more accepting of, and more engaged in sports betting, reported engaging in more sports betting behaviors in the subsequent two-week period. Injunctive norms more strongly predicted young adults’ total number of bets, whereas descriptive norms more strongly predicted total amount wagered and negative consequences. Conclusion. Findings provide foundational evidence for peer influence processes on sports betting behaviors among young adults. These key early-stage findings inform how social norms, and other psychosocial factors, may be leveraged within forthcoming prevention/intervention approaches aimed at stymieing the rapidly growing harms associated with sports betting
Elevated temperatures create bottlenecks in the life history of bull kelp (Nereocystis luetkeana, Phaeophyceae)
No full textThesis (Master's)--University of Washington, 2025The bull kelp Nereocystis luetkeana has declined in parts of the Salish Sea due to local and global change factors, including rising sea surface temperatures. As a foundation species, its loss has broad impacts on biodiversity and nearshore ecosystem function, underscoring the need to identify and address mechanisms of decline. Elevated temperatures affect all stages of the bull kelp life cycle, but it remains unclear whether some stages are more vulnerable than others. To assess stage-specific sensitivity, I examined the effects of four temperatures (10, 12, 15, and 18°C) on the development of gametophytes and young sporophytes cultured from field-collected sori over four weeks. The density of female gametophytes declined significantly at 15°C and 18°C, while the density of male gametophytes remained consistent across temperatures, leading to greatly reduced sex ratios over time. Gametophyte reproductive success was severely limited at 18°C, suggesting a thermal threshold for successful recruitment. Sporophyte production was reduced at 15°C and nearly absent at 18°C, driven by the reductions in the density of female gametophytes and impaired reproductive success at elevated temperatures. These findings reveal critical bottlenecks in bull kelp maturation and recruitment, with serious implications for population persistence and ecosystem resilience in a warming ocean
EXPERIENCING THE SACRED: A phenomenological exploration of architecture as sentient space
No full textThesis (Master's)--University of Washington, 2025Experiencing the Sacred considers how a sense of sacredness in architecture comes from lived, embodied experience, rather than the presence of religious symbols or functions. Utilizing phenomenological thinkers such as Merleau-Ponty, Bachelard, Pallasmaa, and Norberg-Schulz, this thesis investigates how spatial atmosphere, sensory perception, material quality, and movement all contribute to experiences of the sacred.The thesis compares three notable projects – the Lotus Temple in New Delhi, the Chapel of St. Ignatius in Seattle, and the Water Temple in Awaji. In this examination, it draws attention the ways in which architecture can activate an experience of contemplation, stillness, and transcendence via sensory engagement, and elemental forces. Central themes include light and shadow, the notion of ritual movement, spatial thresholds, and the evolving relationship between interior spaces and the natural world.
Ultimately, this thesis argues that sacredness is not restricted to religious buildings, and that sacredness can be awakened in any given architecture with the potential for deep attention, presence, and emotional connection
A Search for Neutral Long-Lived Particles Decaying into Displaced Jets in the ATLAS Calorimeter in Proton-Proton Collisions at the LHC
No full textThesis (Ph.D.)--University of Washington, 2025A search for neutral long-lived particles (LLPs) decaying in the ATLAS hadronic calorimeter using 140 fb^-1 of proton proton collisions at √s = 13 TeV delivered by the LHC is presented. The analysis targets pair-produced LLPs where at least one LLP is produced with sufficiently low boost that its decay products can be resolved as separate jets. No excesses of events relative to the background predictions are observed. Higgs boson branching fractions to pairs of hadronically decaying neutral LLPs larger than 1% are excluded at 95% confidence level for proper decay lengths in the range of 30 cm to 4.5 m depending on the LLP mass, a factor of three improvement on previous searches in the hadronic calorimeter
Optomechanical Integrated Circuits for Efficient Microwave-to-Optical Transduction
No full textThesis (Ph.D.)--University of Washington, 2025Microwave-to-optical transduction is crucial for long-distance data transmission in both clas-sical and quantum networks. In classical applications, microwave-to-optical transduction can be
achieved through electro-optics effect. In quantum applications, cavity-optomechanical systems
with microwave phononic mode are uniquely suitable for this task. However, a scalable platform to
achieve efficient microwave-to-optical transduction is still elusive. This work presents three novel
approaches to address these limitations.
First, a wafer-scale boron-doped gallium phosphide (BGaP) material platform is utilized to
demonstrate scalable optomechanical devices. The BGaP optical resonators exhibit intrinsic quality
factors exceeding 25,000 at visible and 200,000 at telecom wavelengths. It further demonstrates
a low acoustic propagation loss and an integrated acousto-optic frequency shifter (AOFS) using a
zinc oxide (ZnO) hybrid integration. These results show BGaP material as a promising platform
for scalable optomechanical technologies.
Second, we develop a BGaP-based optomechanical integrated circuit (OMIC) featuring the first
ring-type optomechanical cavity—an optomechanical ring resonator (OMR)—in which phononic
and photonic modes co-circulate and interact. The hybrid platform, which combines suspended
BGaP for waveguiding and ZnO for phonon generation, achieved an intermodal conversion efficiency
of ηi = 2.1% at a low acoustic pump power of 1.6 mW. This enables an efficient microwave-to-optical
transduction for quantum information and microwave photonics applications.
Finally, we introduce a non-suspended OMIC using silicon-on-sapphire (SOS), compatible with
state-of-the-art superconducting qubits. By leveraging the triple co-resonance modes, we report
a phonon pump-enhanced coupling rate Gb = 3.6 GHz/mW−1/2 at a low microwave drive power
PMW = 3.6 mW. This is the first OMIC demonstration on a non-suspended material platform
with a GHz pump-enhanced coupling rate, and we project a two-order magnitude improvement
of coupling rate by optimizing the design, which paves the way for an ultra-efficient microwave-
to-optical conversion for quantum interconnect. We conclude by discussing the outlook and the
challenges of OMIC and propose possible ways to improve the OMIC performance for quantum
transduction
Physicochemical Hydrodynamics and Machine Learning Characterization of Isothermal Nucleic Acid Amplification Nucleation Site Analysis
No full textThesis (Ph.D.)--University of Washington, 2025Nucleic acid diagnostics have advanced since PCR's first use in sickle cell and HIV diagnosis in the 1980s. PCR remains the gold standard for detecting SARS-CoV-2 and monitoring HIV viral load but is limited by resource-intensive requirements, making it impractical for low-resource or home settings. My research aims to adapt PCR’s strengths using isothermal nucleic acid amplification for rapid, low-cost diagnostics to support global health.I first present a novel assay combining RPA-based amplification with lateral flow detection, offering PCR-level sensitivity with LFA-like ease. It meets WHO SARS-CoV-2 detection standards, demonstrates high specificity, variant resilience, and uses a simple lysis method suitable for minimal devices.
For HIV viral load monitoring, I developed a buffer-modified recombinase polymerase amplification assay on microfluidic chips using amplification nucleation site analysis (ANSA), where nucleation site counts correlate with nucleic acid input, enabling precise, mobile phone-compatible measurements.
Finally, I describe a machine learning approach using a ResNet-18 model to analyze temporal ANSA data and predict DNA concentrations. Two models classify DNA by clinical groups or log-fold changes. This work supports robust, POC-suitable HIV diagnostics and establishes a platform for broader quantitative nucleic acid testing across global health settings
A Qualitative Evaluation of Healthcare Providers’ Perspectives and Experiences in the Application of the “Responding to Gender-based Violence” Training in Timor-Leste
No full textThesis (Master's)--University of Washington, 2025Introduction: Gender-based violence (GBV) is a pervasive and deeply rooted issue in TimorLeste, where nearly 59% of women experience intimate partner violence in their lifetime.
Despite the existence of national policies, the health sector’s capacity to provide effective,
survivor-centered GBV care remains limited. In response, a training program was developed to
strengthen healthcare providers’ knowledge, attitudes, confidence, and communication skills for
GBV response. This study evaluated the implementation of the GBV training program to
understand its effect and identify key facilitators and barriers to sustained integration within the
health system.
Method: This study used a qualitative study design informed by the Consolidated Framework
for Implementation Research (CFIR), which includes the five domains: (1) Intervention
Characteristics, (2) Outer Setting, (3) Inner Setting, (4) Characteristics of Individuals, and (5)
Implementation. A total of 34 healthcare providers who engaged in the GBV training participated
in the study. Data collection involved 19 in-depth interviews (IDIs) and four focus group
discussions (FGDs) with trained health providers at ten community health centers in Liquica and
Ermera municipalities. All interviews were conducted in Tetum by the principal investigator and
transcribed verbatim. We conducted a thematic analysis using a combination of deductive
coding, based on selected CFIR constructs, and inductive coding to capture unanticipated
insights emerging from the data. Coding and data organization were facilitated using ATLAS.ti
software.
Results: Findings revealed several facilitators and barriers across the CFIR domains. In the
innovation domain, the training was widely perceived as a valuable transformative improvement
to providers’ clinical practice to respond to GBV. Within the individual characteristic domain,
providers reported enhanced confidence and strengthened survivor-centered care following the
training. However, in the process domain, the absence of ongoing learning hindered the
retention and consistent application of GBV response skills. The inner setting domain
highlighted persistent barriers, including limited health resources and inadequate safe space
infrastructure, which constrained effective service delivery. Finally, under the outer setting
domain, cultural norms and community stigma discouraged survivors from seeking care, while a
lack of legal protections posed significant challenges to providers’ ability to respond safely and
confidently to GBV cases.
Conclusion: This study highlights that GBV training can significantly improve healthcare
providers’ confidence, knowledge, and clinical practices in responding to GBV. However,
sustainable implementation requires more than individual-level change. It depends on
addressing systemic barriers. Aligning continuous capacity building with supportive
infrastructure, legal protections, and multisectoral coordination is essential to strengthen GBV
response and ensure accessible, survivor-centered care in Timor-Leste
On Finding Home: Fractures and Dislocations In Memory Through War, Rebirth, and the Ghostly in Trauma
No full textThesis (Master's)--University of Washington, 2025This essay critically examines memory and trauma through my experiences in war and motherhood. I consider violence in war stories and the role of memory and imagination in my work. I question what is possible in finding home and making a life when the past cannot be erased and yet has been forgotten. Within this past, I wonder about grace within what is absent as well as within creation and destruction. This essay creates testimony on the importance of craft as my path to question both what my past means to me now as a new mother and about how my past might create meaning beyond my personal experience? This paper discusses works such as Venus In Two Acts by Saidiya Hartman, The Things They Carried by Tim O’Brien, Home by Toni Morrison, and other works related to war, memory, and the speculative. This paper discusses Korean American identity and generational trauma through Tastes Like War by Grace M. Cho, The Magical Language Of Others by E.J Koh, and other works
Differential Expression of IFN-Gamma Stimulated Antiviral Genes in Human Herpes Simplex Virus Infection
No full textThesis (Master's)--University of Washington, 2025Herpes simplex virus type 2 (HSV-2) causes highly prevalent and recurrent ulcerative disease that affects millions of individuals worldwide. Clinical outcomes vary widely, ranging from asymptomatic, subclinical illness to severe, painful ulcerations. HSV-2 prevalence is further associated with an elevated risk of human immunodeficiency virus (HIV) acquisition, due to the recruitment of HIV-susceptible CD4+ T cells to sites of mucocutaneous infection. As HSV can establish latency in sensory ganglia and reactivate throughout an individual’s lifetime, a host's innate and adaptive immune system must continuously surveil and contain viral activity. Viral containment is primarily attributed to HSV-specific CD8+ T cells that persist at sites of prior infection, alongside the network of chemokines and cytokines that coordinate local antiviral immune responses. Within the herpes lesion microenvironment, interferon gamma (IFN-γ) plays a critical role in viral control by inducing the expression of interferon-stimulated genes (ISGs) in neighboring cells, most notably keratinocytes and fibroblasts, which produce antiviral proteins, microbicidal molecules, phagocytic receptors, and additional immune modulators that help establish an antiviral state. In this study, we investigated donor-dependent IFN–γ–induced gene expression in primary structural cells isolated from individuals with asymptomatic or severe HSV-2 disease. By assessing the transcriptional response of specific ISGs in keratinocytes and fibroblasts exposed to IFN-γ, we identified distinct patterns of gene expression based on both donor phenotype and cell type. Our findings suggest that variability in the magnitude and regulation of IFN-γ-responsive genes may underlie the heterogeneous clinical manifestations of HSV-2 infection. Understanding the mechanisms that govern effective immune control can help us identify determinants of disease severity and inform the development of targeted therapeutic strategies aimed at long-term containment and eradication of HSV-2