Item Details

title

Epigenetic Regulation of the ILK1 Promoter and its Role in Chronic Alcohol Use

author

Bodie, Jessica

abstract

Alcohol use disorder (AUD) is a prevalent mental health condition affecting individuals globally, characterized by the inability to control alcohol consumption despite negative consequences. This disorder poses various health and societal risks incurring in $249 billion cost each year. Despite this, AUD treatments are scarce, and have limited efficacy. Epigenetic signatures in the brain have been linked to addiction disorders such as AUD. Our group previously identified a differentially methylated region upstream of the integrin-linked kinase (ILK) transcription start site in the prefrontal cortex of rhesus macaques following chronic ethanol intake. In addition, ILK was downregulated in drinking subjects. Thus, alcohol may mediate alterations in ILK activity through regulation of epigenetic signatures mapping to its promoter. ILK mediates interactions between the extracellular matrix and intracellular signaling. In the brain, it is involved in synaptic plasticity and growth factor signaling, while its inhibition is linked to addiction1,2. The goal of this research was to determine if regions of the differentially methylated region possess promoter activity and if recruitment of transcriptional activators and epigenetic modifications to these regions can alter ILK expression. In parallel, an in vivo assay will determine the efficacy of an ILK agonist in reducing ethanol intake in mice.

subject

Alcohol

CRISPR

Epigenetics

guide RNA

Integrin-linked kinase (ILK)

transcriptional activation

contributor

Cervera-Juanes, Rita P (advisor)

Hawkins, Greg A (committee member)

Appt, Susan E (committee member)

Chen, Rong (committee member)

Solberg-Woods, Leah (committee member)

date

2024-05-23T08:36:23Z (accessioned)

2024 (issued)

degree

Biomedical Science – MS (discipline)

embargo

2029-05-18 (terms)

2029-05-18 (liftdate)

identifier

http://hdl.handle.net/10339/109451 (uri)

language

en (iso)

publisher

Wake Forest University

type

Thesis