Biomedical Sciences ETDs

Publication Date

Spring 5-15-2026

Abstract

Fetal Alcohol Spectrum Disorders (FASD) are conditions impacting development in children exposed to alcohol in utero. Vascular alterations, including defective angiogenesis and permeability, occur in models of prenatal alcohol exposure (PAE). MiR-150-5p, which inhibits angiogenesis and the BBB, is upregulated in brain microvascular endothelial cells (BMVECs) after PAE. MiR-150-5p inhibition counters alcohol-mediated effects on cultured BMVECs and cortical microvasculature in vivo. Here, the mechanisms by which miR-150-5p levels are increased in BMVECs in PAE are investigated. The hypothesis of this dissertation is that multiple transcriptional and post-transcriptional mechanisms coordinate to upregulate miR-150-5p in BMVECs. A novel epigenetic mechanism of differential gene expression in BMVECs in PAE through active DNA demethylation by TET1 overexpression and the impact of this mechanism on transcriptional activity at the miR-150 promoter is described, and the contributions of KSRP in miR-150-5p maturation and VPS4A and Argonaute proteins in miR-150-5p export in BMVECs in PAE are reported.

Keywords

microRNA, Prenatal Alcohol Exposure, Epigenetics, Cerebrovasculature, Endothelial

Document Type

Dissertation

Language

English

Degree Name

Biomedical Sciences

Level of Degree

Doctoral

Department Name

Biomedical Sciences Graduate Program

First Committee Member (Chair)

Dr. Jay Naik

Second Committee Member

Dr. Amy S. Gardiner

Third Committee Member

Dr. David Linsenbardt

Fourth Committee Member

Dr. Gurdeep Singh

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