Evaluation of and diagnosis based on core needle biopsies at present requires trained pathologists on site for both sample manipulation and analysis of tissue structures. Microfluidic lab-on-chip architectures have been studied for automating cell-level pathology for decades, and the CoreView system developed in Eric Seibel’s lab applies similar technologies at the millimeter scale to tissue level analysis. Pulsatile flow has proven to be a reliable means by which to transport tissue samples without damage or adhesion to the flow channels, and high resolution microscope images can be taken in glass-covered channels for analysis by a remote pathologist or image processing system. I am developing a low cost and manufacturable on chip device to accurately cut and sort these tissue samples for further processing. To avoid unnecessary complexity and unreliability, compliant elastomeric actuators will be employed to actuate an on-chip knife which also acts as a valve controlling transport flow routing. This integrated compact device will achieve all of these goals in a system that can be mass-produced for low-cost and disposability if required for sterility. Such capabilities will enable tumor-rich regions to be sampled for genomic analyses that allow precision therapy, making cancer a treatable disease.

The blood-brain barrier (BBB) is a highly specialized interface of brain microvascular endothelial cells (BECs). The main functions of BECs are to protect the brain against exposure to harmful substances in the blood, and to transport and secrete nutrients and other molecules that support normal brain functions. BECs can also alter their functions in response to signals from the brain or blood compartments. GLUT-1 is the predominant transporter at the BBB that regulates glucose entry into the brain, and does so by a mechanism of facilitated diffusion, which permits glucose transport in the blood-to brain or brain-to-blood direction. GLUT-1 dysfunction occurs in and may contribute to Alzheimer’s disease.The main hypothesis is that GLUT-1 malfunction in the BBB occurs as it deteriorates with age, which causes errors in other regulation methods of the BBB leading to the development of Alzheimer's. However, it is difficult to study mechanisms of GLUT-1 dysfunction at the BBB specifically because of the involvement of multiple cell types that regulate glucose uptake into the brain in vivo. In my research, I have utilized a model of iPSC-derived brain endothelial cells (iBECs) in order to study aspects of GLUT-1 regulation in an in vitro model of the BBB. Currently, my main findings have shown that the GLUT1 transporter is functional in our system, and that GLUT1 protein expression is increased and glycolytic enzymes are decreased when iBECs switch from a proliferative state to a quiescent state. Glucose transport in the blood-to-brain direction is decreased in the quiescent state.  Additionally, high glucose exposure causes downregulation of glucose transport.  My future studies aim to determine whether proliferating vs. quiescent iBECs respond differently to high or low concentrations of glucose. In summary, we have shown that iBECs are a translatable and effective model that allows us to further investigate the regulation of GLUT-1 at the BBB to further understand the physiological mechanisms involved in Alzheimer's Disease. 

Duchenne Muscular Dystrophy (DMD) is a severe muscle wasting disease caused by the deficiency of dystrophin protein affecting ~1 in 3500 boys. Exercise has been investigated as a potential therapy but has shown conflicting effects on dystrophic muscle. Animal models that have been studied but do not fully mimic the disease and cardiac phenotype. Here, we provide the first known evaluation of exercise in a new DMD mdx rat model that mimics skeletal muscle and cardiac pathology. Having an animal model that better reflects the DMD cardiac phenotype is crucial in establishing physical activity guidelines that minimize potential damage to the heart. In Aim I of this pilot study, DMD mdx rats (n=3) and sibling wildtypes (WT; n=3) were assigned to wheel or treadmill exercise training groups (high intensity or low intensity) or unexercised (sedentary) for 6-weeks. Throughout this 6-week period, I was responsible for executing the rat treadmill exercise training protocol at low-to-moderate intensity (5x/week), and monitored the rat wheel running activity. Physiological measurements were conducted pre- and post- training (wheel running, treadmill testing, grip testing, echocardiography, and hindlimb force testing). Compared to wheel running or unexercised rats, treadmill training produced the greatest gain in treadmill exercise endurance testing and in fatigue-resistance in in-vivo hindlimb force testing for DMD rats. However, the treadmill program was associated with severe cardiac effects in DMD mdx, indicated by significant fibrosis and inflammation and echocardiography (Myocardial Performance Index, % fractional shortening and ejection fraction), a finding which will be investigated in subsequent cohorts.

Parkinson’s Disease (PD) is a neurodegenerative disease that affects movement and often leads to tremor, rigidity, and balance issues. Speech impairment, or dysarthria, is also common and may influence many aspects of speech production, such as respiration, articulation, phonation, and prosody. There are currently multiple methods for measuring speech impairment severity over time. Often, severity of dysarthria is captured by neurologists during administration of a global measure of PD severity, the Unified Parkinson’s Disease Rating Scale (UPDRS). This scale uses one question to assess speech impairment severity on a perceptual level, but does not formally evaluate specific characteristics, such as intelligibility. Alternatively, speech-language pathologists may use measures of speech intelligibility to assess dysarthria severity. This method systematically quantifies the extent that speech was understood by a listener. The connection between these two approaches is currently unknown. Therefore, the purpose of this project is to examine the relationship between UPDRS scores and speech intelligibility metrics, two commonly-used indicators of dysarthria severity in PD. Connected speech samples for 27 individuals with idiopathic PD were collected. UPDRS ratings were completed independently by a speech expert who was blinded to intelligibility scores. Speech intelligibility ratings were based on 100-word speech samples and averaged across three listeners. Statistical analyses will include Pearson correlation to determine the strength of this relationship. Expected findings include a significant negative correlation, suggesting that increased severity on the UPDRS (higher score) corresponds to increased severity on the speech intelligibility calculation (lower score). Determining the relationship between these two indicators of speech severity will unite clinical understanding of speech impairment across the fields of neurology and speech-language pathology. This will also indicate whether a single speech severity question equates to more time-intensive intelligibility ratings.

The goal of this project is to develop a dynamically evolving connectionist model that more closely resembles the brain through its information-processing. Over the years, AI has shifted from the first generation of feedforward systems to the use of recurrent or convolutional Neural Networks. The third and newest generation of AI models, the brain-based models, and the Spiking Neural Network (SNN), attempts to bridge the gap between Neuroscience and ML using biologically realistic models like Θ-model, LIF, Izhikevich, HR, HH. These models, however, are still a black box leaving very little control or understanding on the learning process within the system without the access to the inner structure of the network. In addition, these systems are highly inefficient, slow, and very complex due to the limitations imposed by the hardware and explicit simulation of partial differential equations. Real world problems require “flexible learning and dynamically adaptive connectionist systems” that are capable to adapt and accommodate new input in real time. Current solutions have focused on varying the weights within a system rather than focusing on how connections within the system are formed. Based on our understanding from organismal brain structures, our approach, called biomimetic information codec, .bic, is a morphologically-adaptive coding hierarchical network that form in accordance with energy minimization - driven by dissipation of "heat" generated by the training data - constructing cortices and connectome for processing of information. My first objective herein is to quantitatively compare detailed structures between biological (fly brain) and .bic. networks using a random matrix approach.

Neurons in the brain are dynamical in nature, maintaining constantly changing states. Neurons modulate voltage based on input currents and produce spikes when the voltage exceeds a certain threshold. Additional dynamics after spiking, called evoked after-spike currents, are important for computation and memory over time scales. The diversity of neuronal dynamics and the variability in parameters underlying them give rise to rich and varied dynamics across networks. We hypothesize that the complexity and diversity of biological dynamics in the brain play a critical role in predictive coding of temporally complex systems, and that diverse forms of after-spike currents enable computation over variable timescales. Current artificial neural networks (ANNs), that emulate the structure of biological neural networks, successfully learn relationships between static patterns but have difficulty learning dynamic patterns that change over time. We aim to incorporate complex biological dynamics and diversity in ANNs and thereby systematically explore the function of such dynamics in network computation and learning. To this end, we construct ANNs that express biologically realistic dynamics, developing methods to learn dynamics-generating parameters, such as membrane capacitance and threshold, in individual neurons. Theoretically, diverse dynamics of individual neurons will enable even more complex dynamics when combined in networks and may improve performance on tasks requiring computation over complex timescales, such as determining actions based on temporal patterns of cues. Hence, we hypothesize that when trained on temporally challenging tasks, our networks will learn diverse dynamics across neurons. We present the diversity of parameters learned and the resulting distribution of firing patterns and compare performance between our neural networks and traditional networks that only learn connection weights. This research will inform learning methods for training novel biologically inspired neural networks and will also shed light on the physiological role of diversity in the brain.

Skin can detect a wide range of stimuli through the touch system, which is mediated by specific cells and structures. Merkel cells, one of these specialized types of skin cells, sense gentle touch and texture. In mammals, Merkel cells are identified by the expression of the transcription factors Sox2 and Atoh1. Recently, the Rasmussen lab identified Merkel cells in the zebrafish skin that share many characteristics of mammalian Merkel cells, including expression of Sox2 and Atoh1a. Interestingly, a paper by Konig in 2018 also described a novel cell type that expresses serotonin (5-HT), calretinin, and synaptic vesicle glycoprotein 2 (SV2), termed “HCS” cells, within the zebrafish skin. These researchers proposed that HCS cells are a different sensory population than Merkel cells, because of differing visual characteristics between these cells. However, the paper did not present any conclusive evidence, making the relationship between HCS cells and Merkel cells still uncertain. I hypothesized that Merkel cells and HCS cells are actually the same population of cells. I tested my hypothesis using antibody staining and confocal imaging of zebrafish skin. I found that Atoh1a-positive Merkel cells express serotonin and SV2, demonstrating that Merkel cells in zebrafish are the same cells as HCS cells. Overall, my results resolve the identity of recently described sensory cell types in the zebrafish skin. In future research, I hope to use zebrafish Merkel cells as a promising model to better understand touch system development and regeneration.

I invite you to close your eyes and take a deep breath—5 seconds in, 5 seconds out if you can. Deep breathing relaxes us as humans. Through technology I was able to help instigate relaxation, or at least get you thinking about it. I think that’s a beautiful thing technology can do; it can remind us to take a breath, drink water, educate us on perspectives we may never have known, make us observers of art and music. However, it’s no secret that many parts of the online universe have been created to be addicting; the AI algorithms programmed to show each user exactly what will make users scroll another ten minutes. We also know that technology has been a hotbed for hate speech in recent years as well as a place where unrealistic beauty standards (monetized by diet companies) have thrived. In my project I refer to “enchantment" as a bodily connection to the mind, the senses, and to a community. I use this idea of enchantment to explore how various technologies, both modern and traditional, can instigate enchantment, instead of the opposing dis-enchantment. What is technology's connection to catalyzing (re)enchantment in our modern lives and communities? Depression rates are increasing at an alarming rate, especially among teens; I have to wonder if teenagers’ access to social media could be a partial cause of depression, or if for some teens, social media can act as a place of salvation from other possible causes of depression (e.g., school bullying, family issues, etc.). How we interact with the world and how we view ourselves is increasingly dependent on the internet and our global interconnectedness. Technology is becoming more prominent in our daily lives than ever before, how can we make these technological experiences ones that better our lives?

The historical record of the Community, Environment, and Planning (CEP) major, a student-governed program, exists in various formats and locations. The fragmented storage and lack of cohesive narrative prevents prospective students from learning about the major, current students from documenting their experience, and past students from staying connected. This project answers the question "What are the best practices of documenting and sharing the history of an organization, using the Community, Environment, and Planning (CEP) major at the University of Washington as a case study?" The creation of an archive allows for cohesion between cohorts, continuity in storytelling and program improvements, and increased program awareness. The methods used include background research about archives as both a source of information and a subject in their own right, physical and digital archival work, and the creation of a webpage. Analyzing these methods and documenting their application to CEP also informed a framework that guides future archival efforts. Building the archive on the CEP website utilizes existing infrastructure and current visitors to the site. Through digital media and technologies, students can add their stories, access those of past students, and establish connections between them. This archive demonstrates the impact the major has had on students and the greater Seattle area and will provide a platform to help secure programmatic resources, generate prospective student interest, and strengthen alumni connections.

The research question at hand asks how block parties can be used as an empowerment tool to positively affect civic engagement for the Black community. The project lies within the contexts of outreach strategies for underrepresented minority communities; the power of civic engagement and identity; and the inherently political history of the Black community and public space. The primary methods include an in-depth literature review to adequately frame the topic; the interviewing of Black community leaders in applicable disciplines across the United States for their experience and insight; and a creative depiction of the block party re-envisioning into one that centers Black empowerment, learning, and civic amplification. The findings propose a potential solution to magnifying Black voices in civic processes by taking a contemporary approach to the traditional idea of a block party. The final product is the literature review and representation of the Bl*ck Empowerment Party through a virtual zine. These products aim to provide individuals of underrepresented identities with the framework and inspiration to implement the project through discovering innovative methods of public outreach and empowerment rooted in the histories of their own communities in hopes of encouraging engaged citizens. The Bl*ck Empowerment Party addresses the inequities within city structures and development processes through offering a creative solution that honors the rightful space for affected communities to be empowered stakeholders and catalysts.

In the past decade, there has been an increasing focus on the sexual lives of college students. Through this focus, both academic literature and popular culture perpetuate a narrative of “hookup culture” (i.e. environments that accept and facilitate casual sex encounters without romantic or emotional intentions) within this demographic. Though many theories support the importance of studying the sexual lives of college students, this narrative neglects the emotional aspects of intimate relationships, limiting the field’s understanding of intimacy in college. By conducting a thematic analysis of anonymous, written responses from college students (n = 59), this project studied how college students’ perceptions of intimacy differ from the popular narrative of hookup culture and casual sex. Using Erik Erikson’s stages of developmental theory and previous sociological research, I hypothesized that college students will emphasize the emotional components more than the sexual components of their intimate relationships and perceptions. The results of this study expand our understanding of intimate relationships among college students and challenge the limiting narrative of hookup culture and casual sex as ways to study and understand this demographic’s intimate relationships.

Medical tape is used to hold essential devices to the skin for long periods of time. Unfortunately, without means for safe removal, these strong adhesives are painfully removed from the skin, often resulting in medical adhesive-related skin injuries (MARSI). Initial stakeholder interviews have indicated that medical tape removal is painful for the patient, and causes significant anxiety for nurses and caregivers. A 2015 study showed 98.6% of nurses considered skin tears common, occurring in 15% of senior patients and 17% of neonatal patients. A medical tape that offers high adhesion with means for safe removal is needed to eliminate MARSI and increase quality of care. UnTape addresses this need by providing a medical tape that has high adhesion during use but allows for easy and injury-free removal, by simply heating the tape for a few seconds with a heat pack prior to removal. The result is a rapid reduction of the force needed to remove the tape from the patient’s skin without risking MARSI. The tape is formulated with pressure-sensitive adhesive (PSA) that contains an embedded temperature-responsive additive (TRA). The additive will migrate to the surface of the tape upon heating, and melt in the range of 38-43°C, forming puddles that disrupt the adhesive and skin interface. The TRA is selected with a melting temperature that is high enough to avoid accidental peel strength reduction during fever, but below the pain threshold (45-47°C) for skin. Different additives have exhibited over a 50% reduction in peel force. This work focuses on optimization of product definition to yield consistent in vitro testing results, paving the way to clinical studies. The unique properties of UnTape allow for stronger skin adhesion for critical medical devices while eliminating the risk of MARSI upon removal, reducing nurse and patient stress, and providing higher quality medical care.