Author ORCID Identifier
https://orcid.org/0009-0002-8849-0800
Defense Date
2024
Document Type
Thesis
Degree Name
Master of Science
Department
Human and Molecular Genetics
First Advisor
Hamid I. Akbarali, Ph.D.
Abstract
This thesis describes two research projects, both of which explore GI epithelial disruption in distinct settings. The first project addresses the effects of chronic fentanyl exposure on gene expression in colonic crypt cells of the gut epithelium by utilizing RNA sequencing (RNA-Seq). Here we test the hypothesis that chronic treatment with fentanyl leads to selective changes in gene expression that may contribute to GI barrier dysfunction. To assess this, we chronically exposed colonic crypt cells to fentanyl and subsequently performed transcriptomic profiling to identify genes with differential expression compared to controls without exposure.
The second project assesses how disruption to the gastrointestinal epithelial barrier induced by chemotherapy affects the gut microbiome. We focused our analysis on mice treated with irinotecan to examine chemotherapy--induced microbiome alterations. To interrogate the microbiome composition and dynamics in response to irinotecan-mediated epithelial damage, we developed a web-based workflow. Overall, these studies identify molecular and microbial mechanisms by which opioids and chemotherapy disrupt barrier integrity in the gut, with the potential to highlight therapeutic targets to reduce these effects.
Rights
© The Author
Is Part Of
VCU University Archives
Is Part Of
VCU Theses and Dissertations
Date of Submission
12-13-2024