Annual Student Research Poster Session

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  XRK3F2 inhibits p62 signaling and augments myeloma killing by proteasome inhibitors

  Ellen Trautman, Colin Crean, David Halladay, and Attaya Suvannasankha

  Background:

  Despite advancements in therapy, multiple myeloma (MM) remains an incurable blood cancer. Our mission is to maximize the efficacy of a primary treatment for myeloma, proteasome inhibitors (PIs) which cause intracellular waste buildup, leading to ER stress and cell death. p62(sequestosome-1) provides an alternate pathway when the proteasome is inhibited, by breaking down cytotoxic material via autophagy. Upregulation of p62 is associated with PI resistance. We identified a small molecule, XRK3F2, that binds to the ZZ domain of p62 and inhibits its autophagic function. We hypothesized that XRK3F2 would improve MM killing when combined with PIs.

  Methods Used:

  We tested XRK3F2 and PI combinations in vitro, in ex vivo co-cultures, and in a human MM xenograft model. We tested XRK3F2 plus bortezomib in vitro and in ex vivo myeloma: bone cocultures and analyzed effects on tumor burden in a prior mouse xenograft experiment. Results: XRK3F2 induced cell death in various human MM cell lines, with a IC50s of 3-6 M. When combined with carfilzomib, the most potent approved PI, at physiologically relevant doses, there was strong synergy (Combinatorial index of 0.4 to 0.6, by Chou-Talalay analysis). The combination of the two agents significantly increased tumor killing in a tumor: bone co-culture model, where the microenvironment of the tumor provides MM survival signals and potential drug resistance. Enhanced tumor killing was further confirmed in a plasmacytoma model of the human MM cell line RPMI-8226 in NSG mice. We also identified soluble BCMA (B-cell maturation antigen, sBCMA) as a sensitive biomarker for tumor burden, which allowed for serial tumor measurements in all tested models.

  Conclusion and Potential Impact:

  Combining the p62-ZZ domain inhibitor XRK3F2 with PIs shows great promise in improving the killing of MM. Work is ongoing to validate the combination in xenograft models, where tumor cells colonize bones, and in immunocompetent models. Further mechanistic studies using primary MM cells from patients are also ongoing. sBCMA is a cheap, specific, and sensitive tool for serial tumor measurement and should be further validated for preclinical and clinical usage.

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  3D & 360º Visualization in Archaeology

  Amalie Vacanti

  The Trasimeno Regional Archaeological Project (TRAP) is a long-term regional archaeological project focused on the exploration of the Castiglione del Lago territory on the West Side of Lago Trasimeno. The 2023 season involved the excavation of a new site, dubbed the Belvedere site, situated within the town of Castiglione del Lago, Italy, an area of interest due to a visible Roman structure protruding from the earth. With the unique opportunity of working with this new site and the innovations in archaeology that have developed in recent years, this summer’s research focused on the production of digital 3D and 360º content for the Trasimeno Regional Archaeological Site and digital museum, as a means of preserving important information, documenting archaeological context, and creating accessible and interactive content about the excavation.

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  Exploring the Impact of Parental Education and Employment on the Prevalence of ACEs: A Nation Wide Investigation

  Eihi Yoshinaga and Naima Shifa

  Our project seeks to examine the association between caregivers' educational attainment and employment status and the prevalence and types of Adverse Childhood Experiences (ACEs) in their children. ACEs are potentially traumatic events that occurs between the ages of 0 to 17, and it is well-established that ACE exposure is correlated to negative repercussions on mental and physical well-being in adulthood. Our study aims to identify specific caregiver conditions that elevate the likelihood of ACE exposure. Such efforts would allow the facilitation of targeted allocation of ACE-related funding for early prevention and mitigation among high-risk families. We opted to utilize the National Survey of Children's Health (NSCH) data and performed two primary statistical analyses: the Chi-square test and Logistic Regression analysis. Our results revealed clear negative correlations between ACEs and caregiver employment and educational attainment. Our findings provide valuable insights that can inform targeted interventions and support for at-risk families, ultimately working towards the prevention of ACEs and their adverse effects on children's well-being.

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  Phenotyping of Acute Nicotine Response Behavior in Larval Zebrafish

  Mahnoor Zahid and Henning Schneider

  The alpha 3 (chrna3), alpha 5 (chrna5), and beta 4 (chrnb4) receptor genes of the neurotransmitter acetylcholine have been connected to both the onset and heavy smoking in humans. Zebrafish represent a model system for studying the role of genes in behavioral responses to nicotine. The goal of this project was to develop behavioral tests for the characterization of zebrafish gene-knockout mutants that we are developing using CRISPR/Cas9 and zebrafish from the Sanger Mutation Project. Larval zebrafish were used to look at differences in behavior between the wild types and mutated larval zebrafish at different concentrations of nicotine. The different concentrations allowed us to study nicotine sensitivity and acute nicotine response in the larval zebrafish. The acute nicotine response tests and pharmacological treatments with different nicotine cessation drugs and acetylcholine receptor blockers were carried out to determine the effect of the knockout mutation. Overall, the larval zebrafish showed higher movement activity when placed in higher concentrations of nicotine.

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  Nicotine-Seeking and Avoidance Behavior in Zebrafish Mutants

  Lidya Araya, Thanh Ngoc, Thien Nguyen, Daniel Rhodes, and Henning Schneider

  Nicotine activates nicotinic acetylcholine receptors in the brain and peripheral nervous system and triggers nicotine-seeking or nicotine-avoidance. There is evidence from genome-wide association studies in humans that genomic variances of nicotinic acetylcholine receptor genes of the types alpha3 (chrna3), alpha5 (chrna5) and beta 4 (chrnb4) contribute to heavy smoking and early onset of smoking. This project explored the role of the alpha3 nicotinic acetylcholine receptor subunit in nicotine-seeking and avoidance behavior in larval zebrafish. We used zebrafish with the mutant allele sa14384 of the chrna3 gene that represents a missense mutation and causes a stop codon in the alpha3 receptor gene (chrna3). The mutation would affect the function of heteromeric nicotinic acetylcholine receptor types that contain alpha3 subunits such as the alpha3/beta2 and alpha3/beta4 nicotinic acetylcholine receptors. The chrna3 mutant allele (sa14384) was associated differently with nicotine-seekers, nicotine-avoiders and non-seekers. Pre-treatment with a blocker (antagonist) for an alpha3/beta4 receptor in normal wildtype larval zebrafish increased the percentage of nicotine avoiders and reduced the percentage of nicotine seekers at a high nicotine test concentration. Moreover, acute nicotine response experiments using the Daniovision system showed that the alpha3/beta4 acetylcholine receptor blocker causes a reduced response in zebrafish from heterozygous parents. Overall, obtained results indicate that the alpha3 acetylcholine receptor subunit is slightly linked to nicotine seeking and avoidance behavior in larval zebrafish. Discrepancies that we observed could be based on known intricate functions of the alpha3 receptor subunit. To gain better insight into the function of the alpha3 receptor subunit future experiments will employ a larval zebrafish strain with two mutant alleles of the alpha 3 acetylcholine receptor subunit.

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  ChemWeb: A 2D Molecular Builder Game

  Suleman Bashir Baloch and Jeffrey A. Hansen

  The research is based on the development of a 2D molecular builder game for CHEM 120 students. The game allows students to draw and check their structures for a given formula against a database of possible correct structures. The game consists of 8 levels, each based on drawing the maximum possible isomers from a given chemical formula. It is created as a web-based application on React.js. The project shall allow greater liberty and ease to students in drawing structures. In addition, they shall be able to perform self-check for drawn structures which will significantly minimize the assistance required from instructors during classes.

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  Investigating rare genetic variants in a human enzyme

  Ayden Bennet, Delany Collier, Elizabeth Davis, Braden Mallery, Daniel Glimco, Ellen Trautman, Beck Wakefield, Sharon Crary Ph.D, and Daniel Gurnon Ph.D

  Our genome is like a parts-list for all of the molecular machines that make us human. Choose any two people on earth, and their DNA will be 99.9% identical- but in the context of our vast amounts of DNA, 0.1% equates to about 10,000 differences in the makeup of each individual’s machinery. These variations make us unique at the molecular level- but in some cases, they can also cause genetic disease.

  Though there are thousands of rare genetic diseases, most of them are not completely understood. Genetic variants are categorized as pathogenic (or likely pathogenic), benign (or likely benign), or when predictions fail, a “variant of uncertain significance”, or VUS. There are hundreds of thousands of VUS’s, each from a real patient with symptoms that have not been definitively linked to an underlying genetic cause.

  In our lab, we try to make a small impact by studying one protein, linked to one disease, at a time. We create and compare the activities of “normal” and “mutant” versions of the protein with the goal of providing insight into the true impact of each VUS. This summer our focus was on Lactate Dehydrogenase (LDHA), the enzyme responsible for generating the lactic acid that is essential to humans’ ability to maintain intense levels of exercise. Students were able to express and purify 8 different variants of the protein.

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  Latex Induction and Effects of Herbivory on Apocynum cannabinum

  Shiley Claypool, Tim Douglas, and Rose Keith

  Apocynum cannabinum, also known as hemp dogbane, is a species of perennial native to the U.S. This species has been found to be extremely plastic, meaning that its environment has significant effects on its phenotypic traits (Ransom et al. 1998). Plant-herbivore interactions, such as herbivory, can drive this plasticity. One of these responses includes the induction of Latex, a white sappy fluid that exits leaves and stems induced by damage (Agrawal and Konno 2009). This project investigates the effects of early-season vs. late-season herbivory on hemp dogbane, as well as how latex induction is influenced by these plant-herbivore interactions.

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  Inhibiting S100β and Troubleshooting Cell Growth

  Animesh Dali, Suhana Basnyat, Robert Passarelli, and Nipun Chopra

  S100B is a protein that is upregulated in neuronal injury. The upregulation of S100B has been observed to start multiple cascades that result in neuronal death. The inhibition of S100B would be a promising treatment for neuronal injury. In our research, we attempt to do exactly so.

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  Diagnosing the Present with An Ecotopian Lexicon

  Chirag Giri and Adam Liebman

  The book An Ecotopian Lexicon (2019) presents a collection of thirty terms and concepts from speculative fiction, anthropology, and the sociology of subcultures, each explored by a different author. The lexicon intends to address our collective “poverty of imagination” when it comes to avoiding global environmental collapse and building a different world, evidenced by the increasing dominance of apocalyptic narratives in popular culture. Although the book’s primary aim is to explore diverse concepts for imagining better futures, we have analyzed the form and content of the book for what they tell us about the present.

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  High-Risk Behavior of Students Carrying Weapon to School

  Nan Lin Wah Sin Htoo and Naima Shifa

  The rise of personal and mental issues in students has been accompanied by an increase in the number of students carrying guns and the frequency of mass shootings at schools in the US. A recent study (Dong, 2021) pointed out that future researchers should focus on recognizing high-risk youths and tackle their issues early on in life most appropriately according to individual differences such as age and personal circumstances.This research discusses the contributing factors to youths carrying guns to schools and analyzes the high-risk behaviors of students. It was hypothesized that their personal issues such as their mental wellness, high-risk behavior, and attitude towards school correlate with their decision to carry weapons, particularly guns on school property. It is found that the group of students who do not feel safe at school and carry weapons has a higher percentage of students who are showing depression and suicidal symptoms than the overall group of students. These students also tend to get into fights in school or outside school more often. It is also found that students who experience dating violence (sexual or physical), who do binge drinking more often, who have higher sexual activities and higher number of sexual partners, students who were bullied, and those who have been threatened or injured by a weapon at school property with a weapon are also more likely to carry guns than those who are not. The results of the analysis also indicate that the feeling of being unsafe at school has a significant effect on whether students carry guns or not.

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  Linking Historical Redlining Maps to Present‐Day Environmental Hazards in St. Louis

  Margaret Keller and Kenneth L. Brown

  Many of America’s cities were mapped by the Home Owners Loan Corporation (HOLC). This practice led to structurally racist housing policies and practices, namely redlining. The practice of redlining directed both public and private capital to native‐born, white families and away from Black, Latinx, and immigrant families that lived in these areas. While redlining is illegal today due to the Fair Housing Act of 1968, its impact is still evident in the structure of many U.S. cities including St. Louis (Hillier 2015). Today, redlined areas are particularly susceptible to environmental injustices because laws, regulations, governmental programs, and policies inadequately protect the marginalized minority groups living in these communities (Pulido 2015). To better characterize the undue environmental burden placed on the residents living in these redlined communities, this project aims to analyze the spatial relationships between historical HOLC redlining maps, modern-day demographics, and the present‐day environmental hazards such as brownfield sites, superfund sites, hazardous waste sites, and PM2.5 concentrations found in these communities.

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  Extended Duration Studies of Energetic Particles in the Stratosphere

  Ian Kuhl, Ashna Coondiah, and Howard L. Brooks

  The Balloon Assisted Stratospheric Experiments (BASE) program aims to measure atmospheric muon concentration at the Pfotzer Maximum with Geiger Counters carried by weather balloons. The most intense radiation is found at the Pfotzer Maximum 18 - 22 km (11 - 13 mi) above ground level. During this summer, seven flights were conducted to attain maximum time in the Pfotzer Maximum using different strategies like underfilling and multiple balloon systems.

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  High Performance Liquid Chromatography (HPLC) for Ampicillin and Cefuroxime

  Patrick McInerney and Richard Martoglio

  Appropriate levels of an active pharmaceutical ingredient (API) in medicines must be present in a medical product for the patient to receive therapeutic value. High performance liquid chromatography (HPLC) was used to develop a methodology to test for the API in Ampicillin and Cefuroxime drugs. Following the regulations of the Distributed Pharmaceutical Analysis Lab (DPAL) out of Notre Dame system sustainability requirements linearity, precision, accuracy/range, spike/degraded spike, limit of detection /quantitation, tailing factor, and number of theoretical plates were experimentally determined to meet the excepted standards.

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  SD Prisms 2D & 3D: Visualizing the Standard Deviation

  Hieu Nguyen, Tom Nguyen, Mamunur Rashid, and Jyotirmoy Sarkar

  SD Prism is a graphical R package used for visualizing the standard deviation of a data set. Given a raw data set, the standard deviation (SD) is defined as the square root of the sample variance. Sarkar and Rashid (2017) interpret the sample SD as the square root of twice the mean square of all pairwise half deviations between any two sample observations. This interpretation leads to a geometric visualization of the sample SD and a more elementary explanation as to why the denominator in the sample variance is one less than the sample size. In this article, we will explain step by step how to understand it mathematically and how the package implements the methodology to visualize the SD.

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  Method Development for the Analysis of Pharmaceuticals Using High Performance Liquid Chromatography

  To Uyen (Anita) Nguyen and Richard Martoglio

  Since 2013, there have been 1500 reports of counterfeit drugs to WHO, especially from African, American, and European regions 1. Tackling the problem of poor drug quality, the Distributed Pharmaceutical Analysis Lab (DPAL) provides a quality analysis to quantify active pharmaceutical ingredient contents with a goal to trigger a report to the MRA or WHO2. With the support of DPAL, we would like to perform a series of chromatography experiments using the HPLC in order to identify and quantify the active pharmaceutical ingredients (API) of Amoxicillin and Ciprofloxacin.

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  Impact of Urea on Size and Red-Edge Emission Spectroscopy of Reverse Micelles

  Tran Nguyen, Nancy E. Levinger, and Bridget Gourley Ph.D

  We use reverse micelles (RMs) as our model system to study the impact of osmolytes on water at the nanoscale. Reverse micelles are characterized by w0 = [polar component]/[surfactant]. In our experiment, we focus on 5 different w0 (w0 = 1, 5, 10, 20, 40) and 3 concentrations of urea (0.5M, 1M, 2M). The Dynamic Light Scattering (DLS) illustrates a linear relationship between reverse w0 (the ratio) and size. Additionally, the DLS data indicates that the impact of osmolytes on size for small reverse micelles is not significant. Furthermore, Red-Edge Emission Spectroscopy shows a bigger impact on emission for smaller reverse micelles compared to the larger w0 samples.

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  Effects of nitrogen fertilizer on the sugar and ethanol production of C. Sativa

  Aidan Power, Christian Mugisha, Boanerges Bamaca, Asmita Mahara, and Mark Wilkins Ph.D

  With the decrease of fossil fuel-supply and increase of greenhouse gasses, biofuels are needed now more than ever. This includes bioethanol, an alternative fuel that can be made from waste materials, including C. Sativa (commonly known as hemp). The common belief in biological engineering is that the sugars from hemp can attract fermenting organisms to produce the needed ethanol. The question remains, however, of how external factors play into the ethanol production from hemp, such as fertilizer. I tested samples from three plots with different amounts of nitrogen fertilizer to see if the amount of sugar and ethanol varies or remains the same, and through a process of composition analysis of the sugars, pretreatment using an alkaline solution, enzymatic hydrolysis using cellulase, and fermentation using ethanol red, determined some significance regarding more sugars being produced in less fertilized fields. The connection from sugars to ethanol, however, remains to be thoroughly tested, as time constraints prevented me from taking enough samples to find any obvious trends or significance between the three plots. Future studies would include gathering more samples for both sugar and ethanol and redoing all processes in order obtain more reliable results.

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  The Impact of COVID-19 Pandemic on Undergraduate Students’ Interest in the STEM Field

  Zaheen Rashed '24, Yuchen Jiang, Zimo Ma, and Pamela M. Propsom

  The deadly consequences of COVID-19 have been well documented, as have the social, emotional, and cognitive effects. These sequelae extend to the educational system. Much less investigated have been the potential positive outcomes of the pandemic. Given that STEM education relies heavily on hands-on laboratory experiences, STEM students may have been especially impacted by pandemic-imposed remote instruction. We surveyed 392 students at one liberal arts college querying why they continue studying in STEM or leave the STEM disciplines. Because the literature indicates that people of color and those from lower socioeconomic groups were more negatively affected by COVID-19, we hypothesized that students from traditionally marginalized groups in STEM would report greater adverse educational consequences of the pandemic as well; however, this was not borne out by the findings. Across demographic groups, students reported negative impacts of COVID-19, although in a few areas we found that more traditionally “privileged” groups complained of more negative outcomes than traditionally marginalized students did. What was most novel and dramatic in our results were the positive outcomes of the “lockdown” reported by students. These beneficial results were in the areas of enhanced resilience, improved social relationships, greater opportunities, academic improvement, and better mental health. Our paper concludes with recommendations for addressing the negative outcomes of COVID-19 and remote instruction, and for taking advantage of the unexpected positive effects.

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  Magma Mixing in the 874 AD Hrafntinnuhraun Rhyolite Eruption

  Chris Shannon, Kenneth L. Brown, D. McGarvie, and Matthew Looke

  The exposed Icelandic crust contains ~10% rhyolite and ~90% basalt, and there is ample evidence in both recent and ancient rocks of interactions between rhyolitic and basaltic magmas. A spectacular and little-studied example is the c. 874 AD rhyolite eruption of Hrafntinnuhraun at the Torfajökull volcano, where after an initial explosive (Plinian) phase a large rhyolite lava field formed. In this lava field, one vent produced a hybrid lava which is a mechanically mixed blend of approximately 83% rhyolite and 17% basalt.

  Polarized light microscopy was conducted on a suite of Hrafntinnuhraun samples that include flow-banded rhyolites, vesicular basaltic enclaves, and hybrid lavas. The flow-banded rhyolites are nearly aphyric, containing plagioclase and augite phenocrysts, with minor hornblende and biotite. The enclaves contain abundant plagioclase, augite, and olivine. The hybrid lavas contain plagioclase, augite, and olivine, but also contain minor amounts of biotite and hornblende.

  To better evaluate the magma mixing process, one hybrid lava sample (83:17 rhyolite:basalt) was analyzed by EPMA. This sample contains mineral cargos belonging to both the rhyolite and basalt end-member magmas. Plagioclase compositions range from An22 to An87, with anorthite-rich grains displaying resorption textures. Of particular interest are olivine crystals derived from the basalt, which contain Fo-rich (~Fo80) interiors and narrow rims (~5- 10µm) with lower Fo content (~Fo70). Follow-up work on diffusion modelling will hopefully yield a timescale, thus providing valuable and new information on mixing processes in the conduit prior to the eruption and cooling of this hybrid lava.

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  Distal Exposures of the Miocene Peach Spring Tuff in the Marble and Ship Mountains, CA

  Kelsang Shrestha, Matthew Loocke, and Kenneth L. Brown

  The Peach Springs Tuff (PST) is a uniquely identifiable ignimbrite deposit formed by a large caldera-forming volcanic eruption during the early Miocene era. Previous investigations (e.g., Miller et al., 1986; Neilson et al., 1990) have suggested that distal ignimbrite deposits located within the Mojave region of southern California belong to the PST eruptive event. To address this hypothesis, this study investigates ignimbrite samples collected from outcrops within the Marble Mountains (n = 6) and Ship Mountains (n = 8) of southern California. Petrographic analysis reveals the abundance of quartz, sanidine, titanite, hornblende, and biotite in most ignimbrite samples. These mineral phases agree well with previous heavy mineral studies of the PST (Gusa, 1986). Electron Probe Micro-Analysis (EPMA) reveals average biotite, hornblende, and sanidine compositions that closely match PST values. Our data suggests that the ignimbrite deposits in the Marble and Ship mountains are distal exposures of the PST.

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  Introduction to Common Molecular Biological Techniques Used in Research Laboratories

  Dington Tan, Ruitang Deng, Winifer Ali, and Qiwen Chen

  The main techniques used in molecular biology are cloning, PCR (Polymerase Chain Reaction), nucleic acid electrophoresis, DNA microarray analysis, in situ hybridization (HIS), sequencing (Sanger or Next Generation Sequencing (NGS)). Molecular biology techniques are extremely valuable for addressing a wide range of issues impacting the general state of humanity, in addition to investigating fundamental scientific concerns. Applications for molecular biology techniques include the prevention and treatment of disease, the creation of new protein products, and the modification of plants and animals to produce desired phenotypic traits.

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  Outdoor Leadership in New England

  Sarah Tiggleman and Adam Liebman

  How do we expand youths' curiosity and joy for nature in outdoor spaces? During the summer of 2022, I worked at Overland Summers as an outdoor leader guiding 5th and 6th graders through the outdoor spaces of New England. This leadership role allowed me to understand importance of teamwork and independence for young students, and critically analyze what work these types of programs are doing in retrospect to the concept of wilderness.

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  Emotion-Aware Music Recommendation

  Hieu Tran, Tuan Le, Anh Do, Tram Vu, Steven Bogaerts, and Brian T. Howard

  People often listen to songs that match their mood. Thus, an AI music recommendation system that is aware of the user’s emotions is likely to provide a superior user experience to one that is unaware. In this paper, we present an emotion-aware music recommendation system. Multiple models are discussed and evaluated for affect identification from a live image of the user. We propose two models: DRViT, which applies dynamic routing to vision transformers, and InvNet50, which uses involution. All considered models are trained and evaluated on the AffectNet dataset. Each model outputs the user’s estimated valence and arousal under the circumplex model of affect. These values are compared to the valence and arousal values for songs in a Spotify dataset, and the top-five closest-matching songs are presented to the user. Experimental results of the models and user testing are presented.

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  Gender Disparities in NLSY97: Educational Attainment and Income Level

  Ngan Tran and Naima Shifa

  This paper is designed to examine gender differences in education and their impact on education and occupation status, following the research Economic Rationale for Sex Differences in Education conducted by Janice Fanning Madden. Data was collected from the NLSY97 (National Longitudinal Survey) on American youth born between 1980-84. The sample originally included 8,984 respondents when first interviewed in 1997.