May 15, 2020 Mary Gates Hall

equally effective in treating both cardiac and skeletal muscle. SESSION O-1F The cross-platform approach may help to better predict drug efficacy, leading to a reduced rate of failure in clinical trials. HEALTH SENSINGAND MODELING Moreover, this approach may serve as a benchmark for drug discovery in other neuromuscular diseases. Session Moderator: Alex Mariakakis, Computer Science and Engineering 11:00 AM to 12:30 PM SESSION O-2E * Note: Titles in order of presentation.

A Cross Platform Study to Treat Duchenne Muscular PROTEIN BIOCHEMISTRY Dystrophy Session Moderator: Adam Steinbrenner, Biology Aniruddh Saxena, Senior, Bioengineering 1:00 PM to 2:30 PM Mary Gates Scholar, UW Honors Program * Note: Titles in order of presentation. Mentor: David Mack, Rehabilitation Medicine & Bioengineering, Institute for Stem Cell and Regenerative Evolution of a Self-Assembling Synthetic Nucleocapsid Medicine with Enhanced mRNA Packaging Mentor: Shawn Luttrell, Rehabilitation Medicine June Kim, Senior, Bioengineering Levinson Emerging Scholar, Mary Gates Scholar The dystrophin protein protects cardiac and skeletal muscle Mentor: David Baker, Biochemistry from damage during normal contraction and relaxation by Mentor: Issa Yousif, Bioengineering acting as a shock absorber in the cell. Mutations in the dys- trophin gene lead to Duchenne muscular dystrophy (DMD), RNA-based therapeutics have attracted significant interest as an X-linked recessive disease. Boys suffering from the dis- a promising alternative to traditional cancer therapy methods. ease become ventilator dependent at a young age and usu- Coupled with other technologies such as the application of ally succumb to cardiac failure in their thirties. Other symp- nanocarriers, RNA-based treatments have shown the poten- toms of DMD include muscle wasting, cardiomyopathy and tial to regulate gene expression in tumor cells with high ef- respiratory failure. Currently there is no cure for DMD and ficacy and reduced safety risks. Despite these advantages, while gene therapy has shown great promise, it still needs to delivering sufficient amounts of therapeutic cargo while es- be complemented with additional therapeutic interventions in caping from the proteolytic environment of the endosome has order to fully address the symptoms of DMD. Previous work remained a long-standing challenge. This project focuses on by our lab identified several drugs that blocked a certain type addressing this issue by evolving the I53-50-v4 (V4), a self- of calcium channel in cardiac muscle and protected the cells assembling synthetic protein nanoparticle engineered to en- from damage following injury by correcting calcium move- capsulate its own mRNA, to increase RNA packaging and ment into and out of the cell during muscle contraction. In prevent degradation upon endocytosis. With previous data this study, the leading drugs will be tested further using a suggesting a decrease in mRNA encapsulation with an in- cross-platform approach. The drugs will initially be tested in crease in mRNA length, additional designs were generated to cardiac and skeletal muscle differentiated from healthy and further validate this finding. Furthermore, different variations DMD patient-derived induced pluripotent stem cells (iPSCs). of de novo pH-responsive trimers for endosomal escape were The top three drugs that restore normal contraction and re- fused to the exterior of the V4 and tested for RNA packaging. laxation kinetics in vitro will then be tested in the DMDmdx Using computational tools, algorithms were also developed rat. This novel, small animal model has a similar progres- to model the porosity of the nanoparticle and to label residues sion of DMD symptoms to human patients. The rats will for cationic mutations. Protein nanoparticles were expressed be fed the drugs in their chow. Skeletal and cardiac muscle and purified via Immobilized Metal Affinity Chromatography performance will be evaluated to determine whether correct- (IMAC) and SEC (Size Exclusion Chromatography). Con- ing muscle contraction kinetics ameliorates the symptoms of structs were then analyzed in their mRNA encapsulation lev- DMD. Furthermore, we will show whether the same drug is els through RT-qPCR. Success of this project would demon-

Undergraduate Research Program 1 www.uw.edu/undergradresearch strate an increase in encapsulation levels with a decrease in lapse, therefore the results from this experiment can provide mRNA length. As the phenotype of each nanoparticle design prospective molecular pathways to target for future studies in is spatially linked to its genotype, the top performing designs treating opioid withdrawal symptoms. Reducing the severity can also be selected and further evolved using both experi- of withdrawal would thus allow ease in discontinuing opioid mental and computational approaches. This will allow the use and diminish relapse. development of a novel assay for screening desired proteins and narrow the gap towards achieving an efficacious RNA- delivery system. SESSION T-2F

SESSION T-2C MEDICINE,PATHOLOGY, PHARMACOLOGY, AND BIOETHICS PSYCHOLOGY,SOCIAL WORK, 10:05 AM to 10:50 AM * Note: Titles in order of presentation. PSYCHIATRY &BEHAVIORAL SCIENCES Creating a Pre-Transplant Machine Learning Model for Predicting Infection in Patients with Multiple Myeloma 10:05 AM to 10:50 AM Adam Samir Alayli, Senior, Materials Science & Engineering * Note: Titles in order of presentation. Mentor: David Coffey, Department of Medicine

Behavioral Effects of Inhibiting P2Y12 Receptors in Infection is the most common cause of mortality among pa- Microglia during Fentanyl Withdrawal tients with multiple myeloma undergoing autologous stem- Emily K Vo, Senior, Biochemistry, Chemistry cell transplant. Understanding the risk factors that lead to UW Honors Program higher probability of infection is instrumental in their pre- Mentor: John Neumaier, Psychiatry vention. Although some risk factors are known, there are no Mentor: Kevin Coffey, Psychiatry and Behavioral Science robust predictive models for infection among myeloma pa- Mentor: David Bergkamp, Pharmacology tients receiving a hematopoietic stem-cell transplant. In this research study, we compared a variety of machine learning Prescribed opioids are the most common analgesic used for algorithms to reveal clinical features pre-transplant that are alleviating acute and chronic pain. Despite this positive at- most predictive of infection post-transplant. Using features tribute, opioids are also highly abused drugs that can lead to extracted from the electronic health record by means of nat- tolerance and dependence. This abuse has caused a dramatic ural language processing and manual abstraction, we trained increase in opioid overdose-related deaths over the past cou- our model using patients diagnosed with multiple myeloma ple of decades, deeming it a crisis. However, cessation of who received an autologous stem-cell transplant at the Seat- opioid use in tolerant individuals who wish to detoxify can tle Cancer Care Alliance. Along with being robust to missing precipitate severe withdrawal symptoms, often leading to re- data, the model is capable of processing diverse, heteroge- lapse in order to avoid experiencing these negative symptoms. neous data and identifying a class of predictive factors that In recent studies, modulation of neuropathic and neuroinflam- can guide treatment decisions. Preliminary results point to matory responses have been linked to withdrawal symptoms. lab tests such as lymphocyte, neutrophil, and platelet counts As a result, we hypothesized that microglia, the resident im- as the strongest predictive features for infection, and further mune cell of the central nervous system, serve as a potential exploration is underway to understand the full impact of these target for withdrawal treatment. In order to test this, we re- and other features. duced microglial activity by inhibiting the purinergic signal- ing pathway. This was achieved by first exposing mice to es- calating doses of fentanyl over the course of a few days to cre- SESSION T-2H ate tolerance. Then, we administered clopidogrel, a selective antagonist of the P2Y12 receptors which are expressed in mi- croglia, before inducing withdrawal using naloxone. Subse- COMPUTER SCIENCE & quently, in order to quantify whether inhibition of microglial ENGINEERING P2Y12 receptors mitigated naloxone-precipitated withdrawal 10:05 AM to 10:50 AM in fentanyl-tolerant mice, we measured avoidance of the with- * Note: Titles in order of presentation. drawal context with the conditioned place aversion (CPA) test, and evaluated somatic signs of withdrawal with Etho- Vision video analysis. Avoidance of the negative emotional and physical symptoms of withdrawal is a key driver of re-

2 Nightwatch Connect A Hierarchical Approach to Designing Itsumi Joy Niiyama, Senior, Informatics (Human-Computer Three-Dimensional, Symmetric Protein Assemblies Interaction), Industrial Engineering Radhika R. Dalal, Senior, Biology (Molecular, Cellular & Jaesuk (Jae) Lee, Senior, Human Ctr Design & Engr: Data Developmental), Biochemistry Science Mary Gates Scholar, Undergraduate Research Jacob Donald (Jacob) Chan, Senior, Industrial Engineering Conference Travel Awardee Sarah Park, Senior, Sociology Mentor: David Baker, Biochemistry Mentor: David Hendry, Information School Mentor: Una Nattermann, Biochemistry

The goal of this research is to bridge the gap of stereotypes Computational protein design is an emerging field that takes between homeless adults and other community members. In advantage of first principles derived from biological protein- order to do this, we propose a pen pal application where protein interactions and explores the protein space that na- homeless adults can write and exchange letters with adults ture has yet to evolve. The Baker Lab developed a software who are not homeless. The application provides unique card called Rosetta that enables researchers to explore this space templates and a pen pal request system that matches two users and create brand new proteins more stable than those pro- together based on common interests. By building relation- duced in biological systems via evolution. This software has ships through customizable letters, our goal is to create un- been adapted to take advantage of a concept that exists every- derstanding and reduce stereotypes between these groups of where in nature- symmetry. Using this concept, I am building people. The method we are using to create this application higher-order protein assemblies including protein nanocages is Value Sensitive Design. Specifically, we are seeking to ad- and three-dimensional protein crystals. Researchers at the dress the values of storytelling and community, while sup- Baker Lab have developed a hierarchical approach to engi- porting the interests of the key stakeholders, namely home- neer these highly symmetric, complex structures. This hier- less adults, other community members, and Operation Night- archical approach involves combining protein building blocks watch. Because we are partnering with Operation Night- with different symmetric topologies multiple times to facili- watch, a nonprofit organization that assists the homeless, we tate higher-order symmetric assembly of a three-dimensional are constantly in contact with them, seeking to develop the protein crystal. By breaking up crystal symmetries into their pen pal application for their organization. However, the main constituent building blocks, we can design these higher-order focus are the users of the application so we are making sure symmetries with greater accuracy and troubleshoot experi- to include them in the design process allowing them to share mental difficulties by pin-pointing structural deviations along their stories and build relationships through this application. the way. Here, I will describe my experience using this ap- We have interviewed the stakeholders with semi-structured proach to create a protein crystal from symmetric building interviews, completed data analysis, analyzed potential stake- blocks. holder value tensions and the challenges that may come up, designed wireframes, created a high fidelity prototype, and conducted formative user testing. The main features of the SESSION T-3G app are: (1) Getting matched to a pen pal based on a profile; (2) Choosing a letter template and writing a letter; and (3) Re- MEDICINE,PHARMACY,PEDIATRICS, ceiving mail in the inbox. We have kept this application very simple: The focus is on sharing stories and catalyzing new &NEUROLOGY understandings. We are designing and coding the application 10:55 AM to 11:40 AM of the working prototype for the research symposium. * Note: Titles in order of presentation.

Lentivirus Delivery via Jugular Vein Injection Does Not SESSION T-3C Efficiently Transduce the Aorta; Most Transduction Is in Liver and Spleen Kaushik Komandur, Sophomore, Center for Study of Capable BIOCHEMISTRY &CHEMISTRY Youth 10:55 AM to 11:40 AM Mentor: Lianxiang Bi, Medicine * Note: Titles in order of presentation. Mentor: David Dichek, Cardiology

Gene therapy may be an effective way to treat vascular dis- ease. However, current approaches to achieve efficient gene delivery to the blood vessel wall require invasive surgery. Others have reported that high-concentration lentiviral vec- tors injected into the jugular vein preferentially transduce cells in the vascular wall of mice. If reproducible, this ap-

3 proach would be a major advance in vascular gene ther- dismutase 1 knockout (Sod1KO) mice lack superoxide dis- apy. To test reproducibility, we injected high-concentration mutase 1 (an enzyme that converts the oxidant superoxide lentivirus into mouse jugular veins and measured transduc- into hydrogen peroxide and molecular oxygen) resulting in tion 4 days later. Eight mice received 10e8 particles of a an accelerated sarcopenia phenotype. We hypothesize that green-fluorescent protein-expressing lentivirus; six mice re- improving mitochondrial function with SS-31 treatment will ceived vehicle only. Mice were euthanized and their aortas, delay the decline in muscle function in the Sod1KO mice. To hearts, lungs, livers, kidneys, spleens, quadriceps and gas- test this, we administered SS-31 to SOD1KO mice through trocnemius muscles, carotid and femoral arteries were ex- surgically-inserted osmotic pumps for 8 weeks between 3 and cised. These tissues were prepared for DNA analysis (to mea- 4 months of age, the published timeframe for the onset of sure transduction) and histology (to detect GFP expression). skeletal muscle decline in SOD1KO mice. Muscle force gen- Tissues used for DNA analysis were frozen in liquid nitrogen eration and fatigue resistance was tested in vivo in the gas- and DNA was extracted. We used quantitative PCR targeting trocnemius before pump insertion and monthly after pump the GFP gene to measure integrated proviral DNA, which we insertion for 4 months. At the end of the treatment we used quantified as proviral copies per cell. We found a mean of 3 histological and biochemical analyses of mouse tissue sam- proviral copies (range 1-6) per cell in the liver samples and ples to determine skeletal muscle fiber type, metabolite and 13 proviral copies (range 4-28) per cell in the spleen sam- protein concentrations, and muscle fiber respiration and oxi- ples. Essentially no proviral DNA was detected in the liver dant production. We expected SOD1KO mice with SS-31 to or spleen of vehicle-injected mice (p<0.003 for both; limit have a lower rate of decline in muscle force production and of detection 0.3 copies per cell). Proviral DNA was not re- increased fatigue resistance over time, higher max ATP pro- producibly detected in the other organs/tissues listed above. duction, and decreased oxidative stress. The effect of SS-31 Tissue for histology was fixed and embedded in frozen blocks on muscle function, mitochondrial quality, and redox home- for immunostaining. We anticipate that immunostaining will ostasis has exciting potential as a translational therapeutic enable detection or exclusion of lower levels of transduction. treatment for human sarcopenia. Intravenously injected lentiviral vectors seem to efficiently transduce the spleen and liver and do not efficiently trans- duce cells in the blood vessel wall. Our data suggest that SESSION T-4F better vector targeting is needed to deliver gene therapy to the vessel wall by IV injection. MEDICINE,NEUROSURGERY, PEDIATRICS,PATHOLOGY SESSION T-4F 11:45 AM to 12:30 PM * Note: Titles in order of presentation. MEDICINE,NEUROSURGERY, Increasing Therapeutic Transgene Expression by Using PEDIATRICS,PATHOLOGY Cis-Regulatory Modules 11:45 AM to 12:30 PM Ethan Knight, Senior, Neuroscience, Public Health-Global * Note: Titles in order of presentation. Health Mary Gates Scholar The Effect of Mitochondrial Targeted Therapeutic SS-31 Mentor: David Dichek, Cardiology on a Model of Accelerated Sarcopenia Mentor: Meena Sethuraman Kevin Andrew Nguyen, Senior, Biology (Physiology) Atherosclerosis, a cardiovascular disease that results from fat Mary Gates Scholar, UW Honors Program (cholesterol) accumulation in the walls of large arteries, is the Mentor: David Marcinek, Radiology major cause of heart attacks and strokes. Gene therapy, de- Mentor: Matthew Campbell, Radiology livered directly to the artery wall, has the potential to prevent Sarcopenia, the age-related of loss of muscle mass and func- and reverse atherosclerosis by removing cholesterol from the tion, is associated with a decline in quality of life in the el- artery wall. Our group has used gene therapy to prevent and derly and has few effective treatment options. Sarcopenia is reverse atherosclerosis in a rabbit model; however, the effects linked to mitochondrial dysfunction and elevated mitochon- are partial. Reasons for partial success likely include expres- drial oxidant production. We are investigating the role of el- sion of inadequate levels of the therapeutic transgene prod- evated mitochondrial oxidative stress in sarcopenia using a uct (apolipoprotein AI; a protein that removes cellular choles- mitochondrial targeted therapeutic and a mouse model of ac- terol and transports it to the liver for excretion). To address celerated sarcopenia. SS-31 is a mitochondrial targeted pep- this limitation and achieve more-effective gene therapy, we tide that associates with cardiolipin, decreases oxidant pro- hypothesized that incorporation within our gene-transfer vec- duction, and increases ATP production in vivo. Superoxide tors of DNA sequences that activate transcription from nearby

4 gene promoters (sequences known as “cis-regulatory mod- bivariate relationships between whether trainings related to ules or “CRMs”) would increase the amount of apolipopro- cultural competence, humility, and diversity were provided tein AI mRNA transcribed from our vectors. We used a and participant perceptions of cultural competence and un- bioinformatics approach and in vitro measurements of tran- derstanding of the Latinx culture. A preliminary analysis of script levels in cultured vascular cells, to identify 11 potential 18 participants found no significant differences at the p < .05 CRMs within the sequences of 4 highly expressed vascular level. However, trends suggest practitioners who are provided cell genes. Some of these CRMs increased apolipoprotein with training across categories of competence, humility and A1 mRNA levels, but not above levels we had achieved us- diversity were likely to report feeling culturally competent. ing other strategies. We are now repeating this approach, us- Additionally, no meaningful differences were seen in average ing newly available in vivo data generated with single-cell ratings of knowledge of the Latinx culture. Preliminary find- RNA sequencing of vascular tissue and with a separate tech- ings suggest trainings are beneficial for practitioners working nique that identifies highly expressed vascular cell-specific in mental health within the Latinx community, particularly genes. We will use the sequences of highly expressed genes for facilitating cultural competence but not necessarily for in- that we identify, along with bioinformatics tools, to identify creasing knowledge around the Latinx culture. new CRMs that are more likely—than the CRMs identified previously, using in vitro data—to increase apolipoprotein AI transgene expression above previously attained levels. We SESSION T-4H anticipate that incorporation of these CRMs into our gene- therapy vectors will increase the efficacy of our vectors in HIGHER EDUCATION,ETHICS & preventing and reversing atherosclerosis. RESEARCH 11:45 AM to 12:30 PM SESSION T-4G * Note: Titles in order of presentation.

HEALTH SERVICES,PUBLIC HEALTH Improving Awareness, Acceptance and LGBTQ+ Literacy Among Incoming Fraternity and Sorority SCIENCES,ENVIRONMENTAL & Members at the University of Washington OCCUPATIONAL HEALTH SCIENCES Megan Lee, Senior, Environmental Studies, Community, Environment, & Planning 11:45 AM to 12:30 PM Emma Rose Hurring, Senior, Public Health-Global Health * Note: Titles in order of presentation. Mary Gates Scholar Mentor: David Inwards-Breland, Pediatrics, Seattle Practitioners Cultural Competence in Mental Health Children’s Hospital Adely Martinez, Senior, Social Welfare Mentor: Tara Wenger, Division of Genetic Medicine, Mary Gates Scholar University of Washington/Seattle Children’s Hospital Mentor: David La Fazia, Social Work and Nursing Historically, the dominant culture in fraternities and sororities Latinx individuals feel that mainstream mental health ser- has been heteronormative. Prior studies have found mem- vices cannot adequately address their specific needs and that bers of the Greek system have higher levels of intolerance non-Latinx therapists may be insensitive to their psychosocial towards those in the LGBTQ+ community than those outside needs. The Latinx population is a rapidly growing population. of the Greek system. There is little data about the effective- In 33 states they account for 58% of the population; in the re- ness of educational initiatives on LGBTQ+ literacy, aware- maining they account for 7%. As a result of increase in pop- ness and acceptance in the Greek system. Thus, we set out ulation in the United States, there is an urgent need to under- to determine the effectiveness of an educational intervention stand the Latinx culture and create interventions that are ef- to promote LGBTQ+ literacy and attitudes among new fra- fective for Latinx individuals. Studies reveal barriers around ternity and sorority members at the University of Washing- therapists lacking empathy towards Latinx clients, and lack ton. To do this, we administered surveys to incoming fra- of language metaphors in order to translate mental health di- ternity (n=383) and sorority (n=208) members to assess lit- agnosis. To address these gaps, the study aims to discover eracy, awareness and acceptance before and after a standard- what are the barriers and needed supports to promote cul- ized presentation on LGBTQ+ issues developed with content turally competent care by mental health practitioners serving experts from Seattle Children’s Hospital. Post-intervention, Latinx communities. This study uses primary data obtained significantly more participants reporting knowing that there through a quantitative survey from mental health practition- are more than two genders compared to thinking there are ers who are serving or have served Latinx individuals. Chi- only two genders or feeling unsure. More participants cor- square and independent samples t-tests were run to examine rectly defined the acronym LGBTQ after the intervention

5 than before, and significantly more understood the distinc- a negative trait demonstrates that when a group member is tion between gender and sex. More participants understood forcibly reminded of group membership, one of several in- the definition of heteronormative, pansexual and had an im- group behaviors emerges. This appears to remain true in the proved understanding of the difference between transgender case of a dominant group identity, though this area has yet to and cisgender post-intervention. Participants’ level of anx- be thoroughly explored. This and related research suggests iety about their own sexuality did not change from pre- to that the stark reminder of gender duality that is gendered vio- post-intervention, but after the intervention, participants rated lence may also bring psychological behaviors related to group the Greek System as more inclusive of LGBTQ+. After the membership into play. This makes the various theoretical intervention, participants reported feeling significantly more frameworks posited for viewing group identity a potentially prepared if a friend approached them to reveal that they are fruitful place to start identifying the social-psychological in- LGBTQ+. In conclusion, an educational intervention resulted terplay at work in this area, providing the basis for deeper in an increase in LGBTQ+ literacy and self-reports of aware- work on topics across the spectrum of gender. ness and acceptance of LGBTQ peers among incoming Greek system at a large public university. Further research can de- termine if this intervention would be similarly effective in SESSION T-8E different geographic regions, private university settings and potentially help with academic success and wellbeing. ENGINEERING 3:30 PM to 4:15 PM SESSION T-6E * Note: Titles in order of presentation. How Does Editor Interaction Help Build the Spanish PSYCHOLOGY,PEDIATRICS Wikipedia? 1:50 PM to 2:35 PM Diana Victoria (Diana) Davidson, Junior, Japanese * Note: Titles in order of presentation. Undergraduate Research Conference Travel Awardee Nancy Li, Senior, Computer Science (Data Science), Psychology vs. Socialization: Proposing a Framework Linguistics For Studying Societal Attitudes About Gender Violence Melissa Guadarrama, Junior, Pre-Major (Arts & Sciences) Emma Breysse, Sophomore, Psychology, Shoreline Ryder Black, Junior, Pre-Sciences Community College Mentor: David McDonald, Human Centered Design & Mentor: Rachel David, Gender Studies, Shoreline Engineering Community College Mentor: Taryn Bipat

Gender violence is an extreme manifestation of bias. More The English language Wikipedia is notable for its large num- and more, research suggests that attitudes surrounding such ber of articles. However, 288 other active language editions manifestations are likely the product of a combination of ob- of Wikipedia have also developed through the intricate inter- jective psychological mechanisms and more obvious reac- actions of contributing editors. While the editor interactions tions to socialization. This same body of work shows that in the English Wikipedia have been researched extensively, understanding the combination is key to any attempt to effec- these other language editions remain understudied. To un- tively target biased behaviors. When it comes to gender vi- derstand how editors currently come to consensus in article olence and societal attitudes surrounding specific instances, building in the Spanish language, a team of researchers has psychological research barely scratches the surface of this leveraged an existing English framework that depicts how interplay. The nearest researchers have come is in studies power and policies play a role in mass collaboration. Us- pertaining to power dynamics and reactions to stereotypes, ing this English language framework, we are using qualitative with a few related tangents in courtroom-based studies and coding methods to build a unique model of the editor interac- analyses of masculine identity. Database and library searches tions on the Spanish language Wikipedia. The results of this for research in the fields of group theory, gender identity and study will help contribute to a deeper understanding of how a stereotype formation and maintenance confirmed the paucity framework in a different language edition of Wikipedia varies of study and revealed an as-yet unexplored intersection be- from the English. Our preliminary results show that policy tween these fields. This literature review suggests exploring plays a large role in justifying editor decisions for the edits that intersection beginning with research that views gender they make on various articles. Furthermore, our research find- as a group. Studies of gender salience in children show that ings have expanded our knowledge of the issues surrounding where an expectation of gender duality is imposed, group- replication of an English framework in a different language like behaviors emerge. Similar research into the behavior of platform. minority students when a fellow minority student displays

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