Rare Intracranial Tumors (RIT) are a heterogeneous group with unmet medical needs. Although infrequent in individuals, RIT affect millions of people who lack effective disease monitoring and treatment. Frequent chromosome gains and losses are common in cancer, leading to the upregulation of oncogenes and downregulation of tumor-suppressor genes, respectively. Somatic Copy Number Variations (CNVs) affect a greater fraction of the genome than single nucleotide polymorphisms (SNPs) and have been correlated to drug resistance and tumor progression, highlighting a potential prognostic value. Cell-free circulating tumor DNA (ctDNA), which are DNA fragments released by necrotic or apoptotic tumor cells can act as a noninvasive cancer biomarker, offering a potential alternative to invasive tissue biopsies. In the present work, we aim to establish the somatic CNV signature of tumor and matched ctDNA to identify non-invasive tumor-related CNVs that may serve as biomarkers for use in liquid biopsy. We performed Whole Exome Sequencing (WES) in gDNA isolated from tumor tissue and matching ctDNA of 15 patients with RITs (pituitary tumor (n=9), craniopharyngioma (n=2), and meningioma (n=4). Raw reads were assessed for quality (Trimmomatic, FastQC), following alignment against human reference genome GRCh38 (BWA). Aligned reads were sorted and subject to duplicate removal using Picard. CNV profiles will be generated using CNVkit tool. Data analysis and visualization will be performed using R and python. The most promising aspects of liquid biopsy in cancer applications are cancer screening and early diagnosis because they can lead to better survival results and less disease burden. At the end of this work, we hope to identify the CNV signatures shared between tumor tissue and ctDNA, provide novel insights into the pathophysiology of these RITs and ultimately, suggest promising biomarker candidates for liquid biopsy.

Marine heatwaves have altered ecosystems globally, including changing community composition and facilitating the spread of invasive species. In south Puget Sound, Washington (USA), non-native Pacific oysters (Magallana gigas) have been farmed extensively for almost a century and grown in enhancement sites, however, they have only recently recruited in the wild. This study explores how the appearance of Pacific oysters was related to spatially (eight sites) and temporally (decade) warmer summer water temperatures in south Puget Sound and compares oyster persistence across five sites where recruitment occurred. The largest recruitment event from 2012-2020 was in the summer of 2015, in the middle of the east Pacific Blob marine heatwave which led to warm water temperatures off the west coast of North America. Throughout the study period, the number of oyster recruits each year was positively correlated with warmer water temperatures. Oyster population densities differed across the five sites where recruitment occurred and generally declined after 2015, but showed no site by year interactions, which is consistent with spatially-variable recruitment and similar post-recrutiment survival. Mean oyster shell heights also differed among sites, which could reflect different growth trajectories or recreational harvest patterns. This study supports the claim that warming sea surface temperatures may interact with species introductions to change modern biogeography. 

Corepressors are proteins recruited by partner proteins to negatively influence the transcription of genes. TPL is a corepressor from the model plant Arabidopsis thaliana, and while we understand a lot about how TPL works, many mysteries still remain. My project aims to identify other proteins that work with TPL to form a transcriptional repression complex at a single-engineered promoter site. First, we created a synthetic repressor called dCas9-TPL that binds and represses the transcription of the RUBY reporter. The RUBY reporter is a visual marker designed to express throughout the entire plant, turning the green plant a bright purple. Our engineered RUBY line also carries two guide RNA binding sites in its promoter with sequences not found anywhere else in the Arabidopsis genome. This allows dCas9-TPL to bind to and repress this synthetic gene and not affect the transcription of other genes. Many of these plants have morphological phenotypes, and visual screening of the repressed RUBY line showed the plants turn a faint whitish-pink instead of bright purple, signifying that the repression by TPL is working. I have screened mutagenized populations of 40,000 individuals from the validated repressed RUBY plant strains using the Ethyl methanesulfonate (EMS) protocol, which creates new point mutations. I identified 257 individuals from 129 mutagenized families with bright purple organs, which signifies that the RUBY reporter is no longer repressing due to a putative TPL interactor being mutated. I will then proceed to form complementation groups and subsequent DNA sequencing to map the mutations. By identifying regulators of corepressor function in plant biology through downstream whole genome sequencing, I hope to learn principles that can inform cellular engineering across many organisms and better understand why certain mutations associated with transcriptional repression cause developmental defects or diseases like cancer in humans.

Vestibular disorders are prevalent, particularly in aged people, and can cause significant impairment to quality of life including spatial disorientation. The sensory hair cells (HCs) in vestibular end organs sense head motions. Vestibular HCs degenerate as we age. Interestingly, vestibular end organs generate neural signals that terminate in the hippocampus. These connections contribute to the regulation of spatial memory and learning, although the mechanism is not completely understood. We are exploring whether loss of vestibular inputs to the hippocampus affects neurogenesis of granule cells in the dentate gyrus. A prior study showed a gradual increase in proliferative activity of granule cell progenitors after bilateral labyrinthectomy. We wondered if the same effect would occur when vestibular HCs are destroyed and if regeneration of HCs reverses the effect. We used a mouse that enables near complete killing of vestibular HCs upon injection of diphtheria toxin (DT). We administered the cell division tracer, BrdU, to experimental (HC-depleted) and control mice, all of which were adults, using 1) a pulse-fix paradigm to capture cells in the cell cycle or shortly thereafter and 2) a pulse-chase paradigm to study cells that differentiate into neurons. I am counting BrdU-labeled cells in the hippocampal dentate gyrus at different times after HC damage and in undamaged controls. In my poster, I will be presenting preliminary data that tests the hypothesis that we will see increased neurogenesis once HC inputs are lost. Once the study is completed, we hope to determine whether and how vestibular HC destruction and regeneration impact hippocampal neurogenesis. By exploring the relationship between the vestibular system and the hippocampus, we will build our understanding of how spatial orientation is regulated and whether vestibular regeneration can improve spatial orientation, which may inform on how to treat people with vestibular disorders in the future.

Mice with a loss of Notch signaling develop hydrocephalus which is a disease marked by the accumulation of cerebrospinal fluid in the brain. Interestingly, the areas of the brain with little loss of cell adhesion were areas with high levels of Hedgehog signaling. There is currently limited knowledge about the genetic basis of hydrocephalus. My hypothesis is that Hedgehog signaling helps maintain cell adhesion independent of Notch signaling by activating downstream Notch factors. Notch signaling is known to maintain neural progenitor cell (NPC) populations while Hedgehog signaling is responsible for NPC proliferation and differentiation. I differentiated mouse embryonic stem (ES) cells into spinal cord cells and treated the cells with four different Notch inhibitors in varying concentrations. I ran a qPCR measuring the expression of Hes1 and Hes5, two downstream Notch factors and SOX2, a neural progenitor marker along with 2 housekeeping genes. I performed an immunofluorescence experiment with antibodies against two cell adhesion proteins, alpha-catenin and N-cadherin as well as SOX2. Early data shows that with an increase in inhibitor concentration, there is a decrease in Hes expression in treated cells. With Compound E, a Notch inhibitor, there was a decrease in SOX2+ cells and alpha-catenin expression. These results indicate that the loss of cell adhesion may be due to premature differentiation of the NPCs into neurons. This study aims to uncover the mechanisms through which Hedgehog signaling helps maintain cell adhesion, providing insight that could facilitate the development of new therapies to treat congenital hydrocephalus.

Two common craniofacial anomalies are cleft lip and palate, where the lip and roof of the mouth do not form completely, and craniosynostosis, where the soft spots of the skull fuse prematurely. Despite the prevalence of these birth defects, the genetic mechanisms by which they occur are still widely unknown. Hedgehog (Hh) signaling is a core developmental pathway that plays many roles in skull development including functioning as a guidance cue for cranial neural crest cells (cells that provide the foundation for bone and cartilage within the head) and regulating bone ossification (the hardening of the bone by osteoblasts developing into osteocytes). I am exploring the mechanism by which elevated Hh signaling changes cell fates, either through neural crest cells or osteoblasts, to influence craniofacial development. I investigated a mutant embryonic mouse model to identify regions where overexpression of Hh correlates to abnormal craniofacial phenotypes. I explored and measured these phenotypes via imaging, utilizing a genetic Hh reporter mouse line and skeletal stained embryos of various ages. My early qualitative and quantitative observations show patterns of widening midline structure that are seen by the increase in eye spacing and incomplete formation of the nasal and palate regions, as well as regions of premature ossification in the parietal regions of the skull. These findings suggest that elevated Hh signals result in abnormal development of the craniofacial region similar to cleft lip and palate and craniosynostosis. Deriving from these findings, I’m continuing to explore how Hh signaling plays a role in craniofacial development as well as gaining insight into the mechanism in which craniofacial anomalies arise.

Sickle cell disease (SCD) is an autosomal recessive disorder caused by the inheritance of two abnormal hemoglobin genes and can present numerous health complications due to the sickling of red blood cells. It can lead to multiple comorbidities, and can have adverse effects on pregnancy. SCD is very common in Sub Saharan Africa in mainly developing countries, but it can pose risks to pregnant women even in developed countries. There has been conflicting information about whether or not the presence of SCD poses a significant risk to pregnancy outcomes. To analyze this, I systematically reviewed previously published evidence on the effects of SCD on maternal pregnancy outcomes in women from multiple hospitals in different countries from 1973 to 2021. I did a matched comparison of the outcomes between mothers with SCD (HbSS genotype) and mothers without SCD (HbAA genotype) using data from 11 studies. For binary variables, I used log risk ratio as the effect size metric, and for continuous variables, I used standardized mean difference. I hypothesized that the presence of SCD would pose a significant risk to pregnancy and lead to higher occurrences of adverse pregnancy outcomes. I found that there was a significantly higher risk of adverse pregnancy outcomes in mothers with SCD and their offspring, compared to mothers without SCD and their offspring. Perinatal mortality and stillbirths increased significantly with SCD, as well as intrauterine growth restriction, urinary tract infection, eclampsia, and occurrences of preterm delivery and c-section. I found that there was not a significantly higher risk of maternal death and premature rupture of membranes in mothers with SCD, although their risk was higher overall. Proper knowledge of the risks of pregnancy with SCD as well as proper management and treatment of the complications associated with it can improve maternal and fetal outcomes.

Dilated cardiomyopathy (DCM) is a leading cause of heart failure around the world. Inherited mutations cause the left ventricle of the heart to enlarge, thinning the heart muscle wall and decreasing the overall function of the heart. In my research project, I will determine if disrupting fibroblast function by knocking out a key developmental signaling factor, p38, can improve, or even reverse, DCM disease characteristics. Specific Aim 1 will be to determine the effects of p38 knockout-induced fibroblast dysfunction on cardiomyocyte function and structural remodeling in late-stage DCM. The rationale is that myocytes in DCM have poor contraction and structurally remodel to longer, thinner morphologies, which occurs in our DCM mouse model around 4 months of age. I expect to see less of these characteristics with the p38 knockout. Specific Aim 2 will assess cardiac fibroblast proliferation and fibrosis in response to disabling cardiac fibroblast function late into the DCM disease process. The rationale is that studying and observing the dynamics of the fibroblast population is critical when understanding the effects of fibroblasts and the p38 knockout model on DCM. In previous studies, the Davis lab identified that cardiac fibroblasts maladaptively respond to inherited DCM mutations in cardiac myocytes, worsening the whole heart. I expect to see less fibroblast proliferation in the p38 model. P38 is essential for fibroblast signaling pathways and functionality, so by knocking it out I will be able to test if fibroblasts are a viable therapeutic target for patients with DCM.

The properties of an estuary are driven largely by the vertical circulation and stratification patterns resulting from the convergence of dense salt water and less dense fresh water. These density-driven circulation patterns play an important role in the way vital nutrients are distributed throughout the environment to primary-producers. This study focuses on the seasonal variation in salinity and chlorophyll in comparison with river discharge levels of the Snohomish River, at Mount Baker Terminal, WA, within Possession Sound. This site is located 3.6 miles SW of the Snohomish River output near Mukilteo, WA. Salinity, chlorophyll, and depth data were collected from January 2020 to December 2023 using a boat based CTD (EXO SONDE). I participated in the collections from Fall 2020 to December 2023. I also reference the United States Geological Survey (USGS) streamflow data at site number 12150800. I categorized deployments by season (Winter: Dec-Feb; Spring: Mar-May; Summer: Jun-Aug; Fall: Sept-Nov) and utilized RStudio and GGPLOT2 to visualize and analyze my data. Preliminary analysis suggests well-defined haloclines and increased chlorophyll levels during spring months, corresponding with increases in river flow at this time. Decreased stratification, weak haloclines and low chlorophyll levels are conversely observed during summer months, corresponding with consistently low rates of river discharge. This raises questions concerning the impact that seasonal changes in river flow have on primary production at and around the halocline. Further analysis of chlorophyll ranges at the halocline is required to better understand this relationship. Monitoring the impact of river discharge variability and primary production is especially relevant in light of changes in seasonal weather patterns related to climate change.

Escherichia coli (E. coli) abundance is commonly used to indicate water quality and environmental health. The pH of water has been shown to affect the survival of E. coli. Possession Sound is an estuary that faces a wide range of pH (around 7.5-9.0) throughout the year due to alkaline salt water from Puget Sound mixing with acidic fresh water from the Snohomish River. Primary production, organism respiration, nutrient runoff, carbon emissions, and currents also affect pH levels. This study aims to analyze the relationship between pH and E. coli abundance in an estuarine environment. PH and E. coli data was collected from 2018 to 2023 by myself and other Ocean Research College Academy students. PH data was collected with a YSI EXO2 Sonde. E. coli data was collected using a Niskin bottle to obtain water samples which were then transferred to Petri dishes for growing and counting E. coli. My preliminary analysis shows that Possession Sound’s average pH range is around 7.5-8.5, with pH being higher in spring and summer than in fall and winter. Early analysis using Spearman’s Rank Correlation suggests that pH and E. coli have a weak, inverse relationship. There is minimal research on the relationship between pH and E. coli in a marine setting, so my study helps to provide insight into the relationship between E. coli and pH in a unique estuary.

As primary producers, plankton play an important role in the marine environment as the basis of the food chain. Because of this, plankton biodiversity can be an indicator of the health of the ecosystem. As weather patterns change, rising salinity has been documented in marine environments across the globe. This has shown harmful effects in several organisms, including plankton. This study focuses on examining the correlation between salinity and plankton biodiversity across different seasons in Possession Sound located in Everett, Washington. For each site and season I compared biodiversity values with halocline salinity data for each plankton tow. Plankton were collected using horizontal plankton net tows at the halocline and identified based on morphology. I used the Shannon Diversity Index to examine biodiversity of phytoplankton and zooplankton. I collected this data on research cruises held by the Ocean Research College Academy and used historical data collected by previous students. The collected data encompass three sites visited from 2014-2024. Preliminary analysis suggests that biodiversity and salinity will have an inverse relationship. By examining the correlation between salinity and plankton biodiversity, we can begin to understand the potential impacts of rising salinity levels in marine ecosystems.

Nutrients play a large role in marine primary productivity, and fluctuations in concentrations can have large impacts on the health of both marine life and human populations. Phosphates, silicates, nitrates, nitrites, and ammonium are all nutrients which are naturally present and key to the functioning of marine environments; however, negative consequences such as Harmful Algal Blooms (HABs) can occur if concentrations differ too far from normal ranges. Both natural processes and anthropogenic activities influence nutrient concentrations in marine environments, and in estuarine environments, like Possession Sound–part of the Whidbey Basin–the impacts of anthropogenic activities are further magnified due to unique estuarine hydrodynamics and the close proximity to dense human populations. For this study, I analyzed three sites within Possession Sound, looking at nutrient levels in comparison with dissolved oxygen (DO) and chlorophyll concentrations (as a proxy for primary productivity). I collected data during numerous research cruises and used this in tandem with the Ocean Research College Academy (ORCA) historical data set. Water samples were sent to the University of Washington Marine Chemistry Laboratory to measure nutrient concentrations, and chlorophyll and DO data were collected through the use of a conductivity, temperature, and depth (CTD) sensor. Preliminary results suggest a strong seasonal trend in nutrient values, with the lowest abundance occurring during the summer months. I hypothesize that further analysis will suggest an inverse relationship between primary productivity and nutrients. This study can potentially offer insight into the health of the Possession Sound ecosystem by assessing the extent to which dissolved oxygen, chlorophyll, and nutrient concentrations are within normal limits and following expected seasonal patterns.

In response to changing conditions, organisms express genes to optimize the match between their phenotype and the environment. Understanding the mechanisms for how genes are turned on or off is therefore an important research area. One challenge in conducting this research is that many of the proteins involved in regulating gene expression are essential to life, and disrupting their function can lead to death. My research focuses on the essential gene SPT6, which encodes a protein that works with RNA polymerase during the elongation phase of transcription. Recently, the Nemhauser Lab has found that SPT6 also plays a role in transcriptional repression. My project aims to differentiate the role that SPT6 plays in transcriptional activation and repression by disrupting its expression in Arabidopsis. Given that SPT6 mutants do not survive, here I test the use of a new tool that allows me to remove my gene of interest in a particular tissue at a particular time. The tool is based on a molecular switch that relies on serine integrases which can recombine DNA between two specific sequences. So far, I have worked with my mentor to rescue SPT6 mutants with a target that expresses the wild-type version of SPT6. Once the integrase is expressed, the recombination turns off the SPT6 gene and turns on a fluorescent reporter. I express the integrase from a promoter that is active only in the first stages of making a new root, so I can observe the impact of loss of SPT6 function in a cell type unnecessary for plants to survive in lab conditions. This project promotes an understanding of the multiple roles of SPT6 during the transtition from repression to activation, and as SPT6 is highly conserved across eukaryotes, my work in plants may also contribute to understanding human diseases. 

Almost every form of cardiac disease is characterized by fibrosis, or the accumulation of collagen, an extracellular matrix (ECM) protein, secreted by the cardiac fibroblast. The buildup of fibrosis is a major clinical burden, as it contributes to diastolic dysfunction, or the heart’s inability to relax, and arrythmias, or an irregular heartbeat. In previous studies, the Davis lab has found that in chronic injury, the heart likely undergoes minor offenses along with periods of rest which accrue over a lifetime. Even when exposed to repeat injury stimuli, the heart is able to recover, and the cardiac fibroblasts can transcriptionally regress. Yet, what remains unclear is when the heart experiences repetitive stress, which is common with hypertension, will these once-activated cardiac fibroblasts have a more aggressive response? And if so, are the activation cues stored in the primed external environment, or are they intrinsic to the cell? To address this, we developed a fibroblast isolation and injection protocol that will ultimately allow us to isolate discrete populations of fibroblasts and study them in hearts void of injury. Our results found that fibroblasts from donor hearts that were subjected to a myocardial infarction injury were detectable at 4 and 14 days post cardiac injection but had little proliferation. However, there was an increase in host fibroblasts recruited to the graft site, many of which were proliferating, and fibrosis was found within these same regions. These results demonstrate that cardiac fibroblasts from the same strain can be isolated and adoptively transferred to other hearts, without exogenous ECM. We can apply this baseline protocol to further examine fibroblast memory in vivo in a model of intermittent hypertension.

Corepressors are proteins found in all eukaryotes that work with DNA-binding proteins to repress many genes. Keeping some genes off, yet ready to quickly turn of if needed, is essential for development and physiology. Our project aims to identify interacting proteins that work with TPL, a conserved plant corepressor, to form a transcriptional repressor complex. To uncover these proteins, we created a visually screenable plant line containing RUBY, a reporter that expresses throughout the plant, turning it dark pink to purple. We next created a synthetic repressor dCas9-TPL and guide RNA (gRNA) construct that binds to and represses the RUBY reporter. Roots of plants with both constructs appeared whitish-pink, indicating dCas9-TPL is transcriptionally repressing RUBY. We then mutagenized 40,000 individuals from this line using the chemical Ethyl methanesulfonante (EMS), which creates new point mutations in random locations throughout the genome. We identified 257 individuals from 129 mutagenized families with dark pink roots, which show that repression by dCas9-TPL has been impaired. Many of these adult plants had phenotypes in addition to appearing pink, including miniaturization, infertility, and irregular growth patterns, suggesting that the mutations we found are affecting other pathways that require TPL. Using Mendelian genetics, we are currently characterizing the mutation types (i.e. homozygosity, recessive, or dominant) as well as establishing complementation groups. We will then backcross the lines with the parent line to eliminate extraneous mutations and perform whole genome sequencing to determine the precise mutation causing loss of repression. This will also tell us if repression was due to mutating a TPL interactor, or mutating one of our reporter or repressor constructs. By finding genes required for TPL to act as a corepressor, we hope to understand conserved mechanisms of corepressor activity across diverse eukaryotes.

Some genes are on all of the time in most cells, and carry out functions that are essential for life. Unsuprisingly, essential genes are difficult to study, as interfering with their function leads to death. One such critical component is the multi-protein Mediator complex, which is found at every eukaryotic promoter where it coordinates activation of gene expression. My project focuses on one of the core components of the Mediator complex, MEDIATOR21 (MED21). While MED21 is required for gene activation, the Nemhauser Lab recently found that it also plays a role in repression of gene expression through interaction with the corepressor protein TPL. I would like to be able to differentiate the role MED21 plays in activation versus repression using the plant model Arabadopsis. This work is made more complicated by the fact that most mutations in MED21 lead to lethal phenotypes. As an alternative I recently developed a new technology called a molecular switch that turns off MED21 in certain tissues or in reponse to addition of a chemical. The molecular switch relies on the expression of serine integrases that recognize, and recombine the DNA between, two specific DNA sequences. By expressing an integrase portein from a promoter that is only expressed in secondary roots, I can study MED21 loss of function in a small pool of stem cells while the rest of the plant is wild type and healthy. Plants that have undergone this cell-type-specfic switch exhibit several abnormal root phenotypes including agravitropism, increased root formation, and more root hairs. My next experiments include uisng a switch from wild-type MED21 to a mutant form incapable of binding to the corepressor TPL. This study will help us better understand the role MED21 plays in repression versus activation, and how state switching contributes to organogenesis.

Currently, over 6.6 million Americans use walking canes, rollators, and forearm crutches. However, little work has been done to improve the practicality of mobility aids for users. Prior work on modifying these mobility devices has centered around sensing and monitoring user interactions with their mobility device, without changes to the core structure of the devices. Our project aims to explore a set of mobility aid modifications including aesthetics, comfort, and ergonomics. We conducted over 15 qualitative interviews with mobility aid users using phenomenological interviewing strategies to understand user preferences and experiences better and gain feedback on possible adjustments to mobility devices. After qualitative analysis and creating codes based on patterns observed in the interviews analyzed, we identified and compiled unique experiences amongst mobility aid users into a codebook. We then sought to address these observations using fabrication methods such as 3D printing, laser-cutting, and soldering to modify existing mobility devices and develop prototyping materials. Subsequently, we conducted a follow-up design workshop to have users develop modifications and accessory ideas using the tools and templates we provided. Some modifications considered included interactivity stickers, physical feedback mechanisms, and improved mobility aid tip designs. Ultimately, we gained feedback for modifications in future mobility aids research and produced guidelines from our experiences working with mobility devices that can improve community input in accessibility aid research. This work also contributed valuable insights into approaching mobility aid improvements from a Human-Computer Interaction perspective.

Are we happier when we experience more comfortable weather, or do we prefer seasons that provide increased social opportunities? Current studies have shown improvement in mood due to warmer, more tolerable climates or spending more quality time with loved ones. There is a gap in the relation of these two factors combined towards an individual's mood. We hypothesized change in relationship between mood and social activity throughout fall and winter. After our second survey period, we will review and organize data points based on temperatures and climates, time in and out of school sessions for students, levels of socialness, and those who changed their answers after reflecting on the social aspects of the questions. In this study, we surveyed 260 Washington State residents aged 18-64 (M = 24.46, SD = 10.03), 56% from Eastern Washington and 44% from Western in the fall prior to the holiday season (September-November 2023) and again in winter (January-February 2024) to measure changes in mood changes. Both surveys, administered through Qualtrics, asked participants about weather types experienced during each season, followed by a Brief Mood Introspection Scale (BMIS) regarding their last two weeks and the Self-Assessment Manikin (SAM) scale of weather tolerance (0°F-104°F). Participants then were asked about socialness during each season and potential seasonal affective diagnoses. We had two target populations: participants under 23 and those who are students and those who are not students or are 23 or older. We expect students to favor periods not in school regardless of socialness, as opposed to those who are not students, who we expect to favor the times they spend with those they care about over periods of isolation as they tend to have more defined schedules.

While research on burnout has focused specifically on service-oriented roles (e.g., healthcare), recent trends indicate a growing prevalence of burnout in academic settings. Burnout syndrome (BS) is a set of psychological symptoms arising from interplay of chronic occupational stress and individual factors. These symptoms often manifest as emotional exhaustion, depersonalization, and diminished professional satisfaction. Academic burnout has become a concern due to its association with poor academic performance, dropout rates and mental health symptoms (e.g., depression & anxiety). This study employed a pre-and post-design, assessing burnout before and after a burnout management workshop. An online survey via Qualtrics gathered data from community college students in the Pacific Northwest (N = 28, primarily women (78%), aged 16-20 (63%), including dual enrolled high school students. The survey employed a revised Purdue Burnout Questionnaire and collected demographic information. The burnout management workshop, facilitated by two psychology faculty members, addressed burnout facets and various management techniques. We hypothesized that participating students would show improvement after attending the workshop. Initial analysis revealed a reduction in total burnout scores before and after the workshop. Despite a noteworthy decrease, the change did not reach statistical significance. This nonsignificant trend suggests a positive direction, and further qualitative data, scheduled for collection in Spring 2024. Understanding and addressing academic burnout is crucial as it directly correlates with students' academic performance and mental health. By examining burnout in the college setting, we hope to contribute valuable insights that can inform policies and interventions to create a more supportive academic environment. 

In recent years, screen time has become an integral part of daily life for people of all ages, whether that be using social media, entertainment apps, or engaging in various online activities. However, many researchers worry that too much screen time may have negative impacts on one’s well-being, especially when it comes to adolescents and to young adults. This study analyzed the impacts of screen time on college students’ social well-being. The Social Model of Well-Being Scale (Keyes, 1998) was distributed online through Qualtrics. The survey also asked participants to report their average daily screen time and which category their most used application falls into (social media, entertainment, creativity, information and reading, etc.). We hypothesized that higher screen time would negatively impact college students’ social well-being. Participants were aged 18-64 and were students at a public 2-year college in the Pacific Northwest. Participants were recruited through voluntary sampling via recruitment posters around campus and through several psychology professors offering extra credit for participation in the survey. As data collection is still ongoing through the winter, the preliminary results (N = 166) revealed that the average social well-being score was 41.56 (SD = 7.28) with a range of 18-64, with higher scores indicating a greater sense of social well-being including social integration, acceptance, contribution, and cohesion. Cell phone use ranged from 30 minutes to 20 hours a day, with an average of 5.73 hours per day. 63% of the sample also reported social media as their most used application. Our findings will provide insight into the mental health of 2-year college students as it relates to screen time. This information may aid in the development of on-campus resources to decrease screen time and increase social well-being.      

Traumatic brain injury (TBI) is recognized as a risk factor for neurodegenerative diseases, but the underlying mechanisms remain unclear. This study aimed to investigate how localized brain injury alters pathologic protein aggregation associated with neurodegenerative disease, focusing on hyperphosphorylated tau (p-tau) and beta-amyloid deposition in brain parenchyma adjacent to chronic contusion. Using brain donors from the University of Washington Brain Repository, cases with a diagnosis of chronic contusion were identified. Beta-amyloid and p-tau deposition were assessed in sections adjacent to the contusion and in contralateral sections without contusion (internal control). Manual counting and HALO imaging software were utilized to quantify the highest density of neuritic plaques/neurofibrillary tangles and overall deposition of abnormal protein in grey matter, respectively. Statistical analyses were performed to compare deposition in contusion versus control sections. Preliminary data was collected in 9 cases, predominantly male with a median age of 79 years. Neurofibrillary tangles were significantly higher in sections with contusion compared to internal controls (p=0.0188), with a similar trend observed for neuritic plaques (p=0.0723). HALO software analysis confirmed increased deposition of both proteins in the contusion compared to control sections (p=0.0391 for both p-tau and beta-amyloid). These findings support that TBI may modulate neurodegeneration by increasing p-tau and beta-amyloid deposition and underscores the importance of further research into the relationship between TBI and neurodegenerative diseases. Next, I will expand our cohort with more cases from the last few years and plan to compare brain contusion in mid-life to contusion occurring after the age of 65. In addition to assessing abnormal protein deposition, I will also examine the neuroinflammatory response. I expect to find greater levels of neuroinflammation as well as increased tau and beta-amyloid aggregation in the older age group as the neuroinflammatory response becomes prolonged during aging.

Age-related macular degeneration (AMD), a multifactorial eye disease, is distinguished by drusen formation and thickening of Bruch’s membrane. Early onset macular drusen (EOMD) is a rare inherited retinal degeneration with clinical similarity to AMD. EOMD results from genetic variants that cause decreased protein expression levels of complement factor H (CFH) and factor H-like protein 1 (FHL-1). The precise mechanism of drusen formation is unknown, although there are multiple lines of evidence that complement dysregulation and inflammation play a major role. RPE cells derived from EOMD patient induced pluripotent stem cells (iPSCs) can serve as in vitro models for understanding the effects of altered local complement. The complement system is a cascade of proteins and reactions that modulate inflammatory responses for the removal of pathogens. Specific components, such as C3a, could be involved in inflammatory responses that contribute to drusen formation and AMD. The purpose of this project is to observe how increased C3a impacts inflammatory cytokine secretion in EOMD RPE cells. iPSCs were generated from peripheral blood mononuclear cells collected from two patients in an EOMD family and differentiated into RPE cells. Western blot analysis was performed on EOMD and control RPE cells to quantify C3a, CFH, and FHL-1 levels to determine baseline expression levels. Control and EOMD RPE were treated with C3a, and inflammatory cytokine (IL-6 and IL-8) secretion was measured by ELISA. Decreased CFH/FHL-1 secretion and increased local C3a were observed in EOMD RPE. Preliminary data indicate that increased C3a levels may alter cytokine secretion by RPE, indicating that increased complement may play a role in local inflammatory responses that contribute to the pathophysiology of EOMD and AMD.

Age-related macular degeneration (AMD) is an acquired degeneration of the retina characterized by the presence of lipid-rich deposits, or drusen, underneath the retinal pigment epithelium (RPE). Development of drusen has been linked to degradation of extracellular matrices and aberrant RPE lipid metabolism. Mutations in tissue inhibitor of metalloproteinase 3 (TIMP3), involved in extracellular matrix (ECM) degradation, have been associated with Sorsby Fundus Dystrophy (SFD), an autosomal dominant inherited disease phenotypically similar to AMD. SFD and AMD share clinical features, such as the presence of drusen, geographic atrophy, and choroidal neovascularization. The aim of this project is to evaluate the hypothesis that increased ECM degradation results in reprograming of SFD RPE metabolism towards increased branched chain amino acid (BCAA) oxidation, resulting in lipid synthesis and deposition. We found that SFD induced pluripotent stem cells (iPSC)-RPE have increased apolipoprotein E deposits, and may have increased lipid metabolism. SFD RPE were found to have decreased levels of FABP7, a lipid binding protein that regulates lipid metabolism by increasing fatty acid oxidation, by proteomics and confirmed by Western blot. SFD RPE cells show increased BCAA consumption and upregulated expression of branched chain amino acid transaminase 1 (BCAT1), an enzyme that catalyzes the animation of BCAAs. Control RPE were treated with BCAT1 inhibitors, BCATc Inhibitor 2 and gabapentin. Treatment of RPE with 50 µM of BCATc Inhibitor 2 resulted in a greater than two-fold decrease in BCAA consumption at 48 hours, indicating effective inhibition of BCAT1. Results from this study will help determine whether enhanced BCAA oxidation results in activation of increased lipid synthesis and lipid deposits in SFD iPSC RPE.