The 5-year survival rate for late-stage metastatic melanoma is only ~30%. A major reason for this low survival rate is that one of the most commonly mutated genes in melanoma, NRAS, has no FDA-approved targeted therapies. Because the RAS protein does not have any targeted therapies, patients with RAS mutant tumors have an ongoing need for treatments that indirectly target RAS. This thesis project aims to identify expression and phosphorylation levels of proteins downstream of RAS in melanoma cell lines with the most common driver mutations. By analyzing the protein-level differences between these genetic mutants, we hope to identify additional indirect RAS protein targets for the treatment of NRAS mutant melanoma. RAS has several downstream effector proteins involved in oncogenic signaling pathways including FAK, Paxillin, AKT, and ERK. 5 melanoma cell lines (2 BRAF mutant, 2 NRAS mutant, and 1 designated wildtype) were analyzed using western bloting for FAK, Paxillin, AKT, and ERK phosphorylation and total expression levels. The results of western blot analysis showed that NRAS mutant cell lines had increased expression of phosphorylated Paxillin. Increased Paxillin phosphorylation corresponds to increased Paxillin binding at the FAT domain of FAK. Therefore, cell lines with increased FAK FAT – Paxillin interaction would be more sensitive to FAK FAT domain inhibition. The data presented provide an an explanation for the reduction in cell viability in NRAS mutant cell lines infected with Ad-FRNK. This information also has significant clinical relevance as researchers work to develop synthetic FAK FAT domain inhibitors, such as cyclic peptides. Additionally, cell lines with high levels of phosphorylated AKT showed a significant reduction in the amount of phosphorylated ERK. The identification of this inverse relationship may help to explain why BRAF and NRAS mutations are mutually exclusive. To conclude, NRAS mutant cell lines have increased expression of phosphorylated Paxillin and AKT which may explain why NRAS mutant cell lines are more sensitive to FAK FAT domain inhibition.

There is increasing interest in understanding how active learning affects students’ mental health as science courses transition from traditional lecture to active learning. Prior research has found that active learning can both alleviate and exacerbate undergraduate mental health problems. Existing studies have only examined the relationship between active learning and anxiety. No studies have examined the relationship between active learning and undergraduate depression. To address this gap in the literature, we conducted hour-long exploratory interviews with 29 students with depression who had taken active learning science courses across six U.S. institutions. We probed what aspects of active learning practices exacerbate or alleviate depressive symptoms and how students’ depression affects their experiences in active learning. We found that aspects of active learning practices exacerbate and alleviate students’ depressive symptoms, and depression negatively impacts students’ experiences in active learning. The underlying aspects of active learning practices that impact students’ depression fall into four overarching categories: inherently social, inherently engaging, opportunities to compare selves to others, and opportunities to validate or invalidate intelligence. We hope that by better understanding the experiences of undergraduates with depression in active learning courses we can create more inclusive learning environments for these students.

Mental health conditions can impact college students’ social and academic achievements. As such, students may disclose mental illnesses on medical school applications. Yet, no study has investigated to what extent disclosure of a mental health condition impacts medical school acceptance. We designed an audit study to address this gap. We surveyed 99 potential admissions committee members from at least 43 unique M.D.-granting schools in the U.S. Participants rated a fictitious portion of a medical school application on acceptability, competence, and likeability. They were randomly assigned to a condition: an application that explained a low semester GPA due to a mental health condition, an application that explained a low semester GPA due to a physical health condition, or an application that had a low semester GPA but did not describe any health condition. Using ANOVAs, multinomial regression, and open-coding, we found that committee members do not rate applications lower when a mental health condition is revealed. When asked about their concerns regarding the application, 27.0% of participants who received an application that revealed a mental health condition mentioned it as a concern; 14.7% of participants who received an application that revealed a physical health condition mentioned it as a concern. Committee members were also asked about when revealing a mental health condition would be beneficial and when it would be detrimental. This work indicates that medical school admissions committee members do not exhibit a bias towards mental health conditions and provides recommendations on how to discuss mental illness on medical school applications.

Under the direction of Dr. Carolyn Compton, a group of seven Barrett honors students have embarked on a truly unique team thesis project to create a documentary on the process of creating a COVID-19 testing laboratory. This documentary tells the story of the ASU Biodesign Clinical Testing Laboratory (ABCTL), the first lab in the western United States to offer public saliva testing to identify the presence of COVID-19.