Honors Theses
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Item Open Access Analysis of tyrosine kinase inhibitor responses in mixed murine EML4-ALK-driven lung tumors to define dominance of their tumor immune microenvironments(Colorado State University. Libraries, 2024) Prosceno, Isabella, authorLung cancer is the leading cause of cancer-related deaths in the U.S. In recent studies, successes in precision oncology with tyrosine kinase inhibitors (TKIs) have yielded marked and durable tumor responses in tumor subsets defined by oncogenic mutations in the receptor tyrosine kinases (RTKs) EGFR, ALK, ROS1, and RET. Despite this progress, most patients show a partial response and these therapies fail to completely eliminate "drug tolerant persisters" also known as "residual disease". Thus, new therapeutic strategies are needed as presently there are no approved therapies after EGFR mutant lung cancer progression on the 3rd generation TKI, Osimertinib. This desperate need for additional precision therapies is crucial for 2nd and 3rd line therapies in oncogene-driven lung cancer patients. Anti-PD1/PD-L1 agents are approved treatments in lung cancers that disrupt tumor-mediated immune suppression. However, these drugs are ineffective in patients whose tumors bear oncogenic RTK genes despite evidence that adaptive immune cells contribute to the anti-cancer activity of TKIs in these cancers. In other words, immune checkpoint inhibitors are not able to be utilized. The Nemenoff and Heasley labs of University of Colorado Anschutz have generated a panel of murine EML4-ALK cell lines (EA1, EA2) that can be orthotopically implanted in immune competent mice. In order to address the question of immune dominance within a mixed EML4-ALK tumor, a project will deploy mixtures of EA1 and EA2 cell lines to intentionally establish heterogeneous tumors and assess the resulting immune microenvironment and the Alectinib response. The lab has generated EA1 and EA2 cells that incorporate specific fluorescent tags, allowing the assessment of each population in mice. In studying heterogeneous lung tumors composed of clones that avidly recruit anti-tumorigenic T cells and clones that recruit immune suppressive cells (neutrophils), we imagine that three different possibilities may be observed. Complete results are not available due to the experiment being ongoing, but it is hypothesized that the microenvironment of EA1 will suppress that of EA2's. This result will show only a partial response to Alectinib.Item Open Access Investigating the impact of undergraduate laboratory courses, research experiences, and CUREs courses on lecture-based course material(Colorado State University. Libraries, 2024) Dirks, Kaitlyn, authorUndergraduate STEM degrees are composed of lecture and laboratory classes. Additionally, undergraduate research experiences and core-based undergraduate research experience (CURE) are becoming more encouraged throughout a bachelor's degree. However, what is the impact of these courses and experiences on undergraduate education? This study aims to understand the benefit or lack thereof, of laboratory courses, CUREs courses, and undergraduate research experience, on that of lecture courses within STEM degrees. The results were collected by a survey and analyzed for statistical significance using the chi-squared test. Results found that both laboratory courses and undergraduate research experiences had an impact on the lecture courses. This correlation could occur from the re-iteration of the lecture course material within the lab course setting. Further the autonomy in a research experience challenges students to engage in critical thinking, application and analysis of the lecture course material. The results pertaining to the CUREs courses are currently incomplete. There were significantly few respondents who had engaged in a CUREs lab. This could have resulted from the lack of knowledge or awareness of the course. With the continuation of lab courses and a required entry level course focused on entering STEM students into undergraduate research experiences, STEM students' academic output could continue to rise. With a better spread of the CUREs course, the data could be recollected and reassessed.