ORCID
https://orcid.org/0009-0002-1539-6143
Date of Award
2026
Document Type
Thesis
Degree Name
MS in Neuroscience
Department
Biological Sciences
First Advisor
Robert Kozol
Second Advisor
Matteo Ruggiu
Third Advisor
Xue Mei
Abstract
Gene-drug interactions are fundamental to understanding variability in drug response and therapeutic efficacy. In this project, we leverage the natural genetic divergence between ecotype morphs of the blind Mexican cavefish (Astyanax mexicanus) to investigate differential responses to neuroactive compounds—specifically, the convulsant pentylenetetrazol (PTZ) and the anxiolytic Buspirone Hydrochloride. Astyanax Mexicanus is a tetra species consisting of both surface-dwelling (ancestral) and cave-dwelling (mutant) populations that have highly variable genetic backgrounds. Independently evolved populations of cavefish exhibit a suite of convergent traits that can be functionally interrogated to discover new genetic functions and interactions. These attributes make A. mexicanus an ideal model for probing gene-drug interactions in the context of drug efficacy and discovering novel pathways for already approved FDA drugs. We created this pilot project as a proof-of-concept, utilizing past genetic discoveries in serotonin metabolism and theories on brain homeostasis to demonstrate the utility of larger drug library screens. Our dilution series and behavioral assays revealed that cave-dwelling populations show resistance to the anxiolytic effect of Buspirone and a surprising change in pentylenetetrazol effects at low and high doses. We are now analyzing the variation in behavior using high-speed kinematics to determine how these gene-drug interactions impact circuit choice and output. Our research describes a new gene-drug model for elucidating unknown interactions between pharmacology and the vertebrate genome. Keywords: Astyanax mexicanus, Behavioral genetics, Gene-drug interactions, Buspirone hydrochloride, mono-amine oxidase 1 (MAO), Pentylenetetrazol (PTZ), Grin2B
Recommended Citation
Gbarlea, Jerry Nawongbay, "UTILIZING A GENETICALLY DIVERSE SPECIES TO INVESTIGATE GENE-DRUG INTERACTIONS AND DRUG EFFICACY" (2026). Theses and Dissertations. 1024.
https://scholar.stjohns.edu/theses_dissertations/1024