Author ORCID Identifier

https://orcid.org/0000-0002-5349-3561

Semester

Summer

Date of Graduation

2024

Document Type

Dissertation

Degree Type

PhD

College

Statler College of Engineering and Mineral Resources

Department

Chemical and Biomedical Engineering

Committee Chair

David J. Klinke II

Committee Co-Chair

Lizzie Y. Santiago

Committee Member

Lizzie Y. Santiago

Committee Member

Tracy Liu

Committee Member

Gangqing Hu

Committee Member

Margaret Bennewitz

Abstract

Quantitative Systems Pharmacology (QSP) refers to a mechanistic modeling approach used for assessing potential therapeutics by linking the molecular and cellular level mechanisms of the disease and therapeutic to the system-wide dynamics and clinical endpoints relevant to the disease. Although the field of QSP is still in its relative infancy, the mathematical methodology employed to predict the kinetics of these systems are not new and can be applied to a wide variety of systems. For instance, similar to QSP’s goal of guiding the development of novel therapeutics for various disease states, there exists a need to develop novel interventions in the engineering education space that can be guided using similar methodologies.

This body of work aims to apply Bayesian statistics, a cornerstone methodology within QSP, in both cancer immunology and first-year engineering education. The first study focuses on four secreted factors identified in a previous study that potentially mediate immunosuppression and could become targets for novel immunotherapies. We tested for clinical correlates in existing human data and verified in vivo whether knocking out tumor cell production of these factors improved immune-mediated control of tumor growth. A kinetic analysis leveraging III a Markov Chain Monte Carlo (MCMC) approach quantified the various knockouts’ effect on cells’ intrinsic growth rate. Key results suggest that CCN4 is a mediator of immunosuppression in the melanoma tumor microenvironment and a potential collateral immunotherapy target.

The remaining two studies focus on improving the performance and retention of non-calculus ready first-year engineering students. As college readiness continues to decline, the proportion of students entering engineering programs with low mathematics proficiency is increasing. These students have lower retention rates than their calculus-ready peers. We created two first-year engineering courses, one college algebra-based course focused on improving critical thinking skills and one trigonometry-based course focused on improving metacognition skills and used Bayesian methods to analyze the impact of the intervention on various student success metrics. Students in both courses saw higher pass rates in their math course compared to the control group. Those participating in the college algebra-based intervention course saw improved critical thinking skills and increased cumulative GPA and retention in engineering. Improvement of skills in the trigonometry-based course was dependent on additional factors such as the difficulty level of the problem analyzed. Preliminary data indicates that combining these courses into a two-semester long intervention could provide improved benefit to the population of non-calculus ready engineering students and improve their success in engineering.

Embargo Reason

Publication Pending

Available for download on Tuesday, July 22, 2025

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