Graduation Year

2026

Document Type

Campus Only Senior Thesis

Degree Name

Bachelor of Arts

Department

Biology

Reader 1

Pete Chandrangsu

Reader 2

Larry Grill

Rights Information

© 2026 Marcella Bustamante

Abstract

Cancer remains a leading cause of death worldwide, with 50% of tumors harboring mutations in the TP53 gene, resulting in loss of function of the tumor suppressor protein, p53. As a central regulator of genomic stability, p53 coordinates cellular responses to stress by inducing cell cycle arrest, DNA repair, or apoptosis. Restoring functional p53 activity in cancer cells is a promising therapeutic strategy; however, the effectiveness of these approaches depends not only on successful gene delivery but also on the dynamics of p53 expression overtime.

This study aims to investigate how gene delivery platforms influence p53 expression kinetics and apoptotic responses. Specifically, nanoparticle-mediated delivery of TP53 mRNA will be compared to adenoviral delivery of TP53 DNA in TP53-null H1299 epithelial cells. These platforms are expected to produce different expression profiles, with nanoparticle delivery allowing for rapid but transient p53 expression, and adenoviral delivery resulting in slower onset but more sustained expression. P53 levels will be measured over time using Western blot and immunofluorescence, while apoptosis will be assessed using Annexin V staining and TUNEL assays.

It is hypothesized that differences in expression kinetics will directly influence cellular outcomes. Transient p53 expression is expected to induce cell cycle arrest, whereas sustained expression is predicted to maintain signaling above the apoptotic threshold, which promotes activation of pro-apoptotic pathways and increased cell death. These outcomes would support the model that p53 functions as a threshold dependent regulator of cell fate, in which both the magnitude and duration of expression determine whether cells undergo repair or commit to apoptosis.

Overall, this proposed study aims to determine how difference in gene delivery methods affect p53 expression dynamics and therapeutic effectiveness.

Download

This thesis is restricted to the Claremont Colleges current faculty, students, and staff.

Share

COinS