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Original Publication Date
2026
Document Type
Video
Abstract
Approximately 50% of the human genome consists of transposable elements (TEs), or "jumping genes"—repetitive DNA sequences capable of relocating within the genome. While the mammalian genome has evolved to silence these elements via KRAB-containing zinc finger proteins (KRAB-ZFPs) and the corepressor TRIM28 to maintain genomic stability, the breakdown of this silencing mechanism is linked to various pathologies. This dissertation research explores a novel frontier in neuroscience: the role of TE stability within the nucleus accumbens (NAc)—a primary hub of the brain's reward circuitry—in mediating behavioral adaptations to drugs of abuse.
Key Experimental Findings:
- Reward Association (Conditioned Place Preference): Initial results in male mice suggests that while control groups find cocaine naturally rewarding, the synthetic activation of TEs via TRIM28 VPR appears to decrease reward association, with mice showing a potential preference for the saline-paired chamber.
- Reinforcement (Intravenous Self-Administration): Using the "gold standard" for measuring voluntary drug-taking, mice were trained to lever-press for cocaine infusions. Preliminary dose-response curves following NAc viral infusion are currently being optimized to determine how TE instability alters the reinforcing strength of stimulants and opioids.
- Mechanism: The study aims to determine if TRIM28-mediated regulation of TEs is a shared mechanism across different drug classes (cocaine/stimulants and morphine/opioids) or a drug-specific adaptation.
Keywords
Transposable elements (TEs), Jumping genes, Nucleus accumbens, TRIM28, Substance use disorder
Rights
Copyright © 2026 Annalise Hassan. All rights reserved.
Comments
Presented in the Next-Generation Medical Therapies session.