Date Approved
1-9-2025
Embargo Period
2-5-2026
Document Type
Dissertation
Degree Name
Doctor of Philosophy (Ph.D.)
Department
Biomedical Engineering
College
Henry M. Rowan College of Engineering
Advisor
Mary Staehle, PhD
Committee Member 1
Joshua Leonard
Committee Member 2
Mary Alpaugh
Committee Member 3
Peter Galie, PhD
Committee Member 4
Sebastian Vega, PhD
Keywords
Biosensor;Immunoengineering;Synthetic Biology;Theranostics
Abstract
Cancer is a complex disease that leads to over 600,000 deaths in the United States each year. Immunoengineering, the process of harnessing a patient's immune system to treat disease, has proven to be a promising therapeutic approach for cancer. For example, the FDA has approved seven chimeric antigen receptor T-cell (CAR-T) therapies. However, these therapies address less than 11% of cancers diagnosed in the United States. In this work, we develop innovative tools to enhance immunoengineering and the efficacy of cell therapies like CAR-T. We introduce and validate synthetic phosphorylation networks with fluorescent and luminescent extension (SPN-FLUX), a synthetic receptor applicable to both immunoengineering and broader synthetic biology tools. We modify SPN-FLUX to function as a biosensor for hypoxia in the tumor microenvironment, an intrinsic feature of nearly all solid cancers and investigate whether we can exploit the native dynamics of hypoxia as a mechanism for cellular therapies to discriminate between healthy and cancerous tissues. Finally, we begin to translate the techniques used in synthetic receptor and biosensor development into computational methodologies. Using computational modeling and docking software, we generate predictions that align with the experimentally obtained preclinical data that were utilized to initiate the Brainchild-01 clinical trial, thereby demonstrating the exciting potential for this in-silico methodology to accelerate the development of life-saving therapies.
Recommended Citation
Davis, Leah Nicole, "Novel Synthetic Circuits for Cellular Theranostic Applications" (2025). Theses and Dissertations. 3321.
https://rdw.rowan.edu/etd/3321
