Aurelio Galli
University of Alabama at Birmingham, AL·Neuroscience
Amphetamines are prescribed for conditions such as attention deficit disorders, but they are also widely misused, with devastating results. Much of their effect comes from the dopamine transporter (DAT), a membrane protein that normally pulls the brain chemical dopamine back into nerve endings.
- Fields
Neuroscience
Pharmacology
Biophysics
- Topics
amphetamine
psychostimulants
substance use disorder
- Grants
- 3 known grants, through Mar 2030
What they work on
- Determine how the N-terminus of the human dopamine transporter binds syntaxin 1 (Stx1), a membrane protein involved in neurotransmitter release, and how amphetamine-induced phosphorylation of Stx1 controls this binding.
- Test whether Stx1 is required for amphetamine-induced dopamine efflux and behaviors such as locomotion, grooming and drug preference, using neurons, isolated Drosophila brains and humanized flies expressing human DAT.
- Test whether the HIV protein Tat, which binds the membrane lipid PIP2, disrupts PIP2–dopamine transporter contacts, weakens amphetamine-induced dopamine efflux and thereby promotes escalating amphetamine use.
- Determine how gut bacterium Fusobacterium nucleatum raises fly dopamine transporter levels, testing whether its product butyrate blocks HDAC gene-silencing enzymes and opens up the DAT gene promoter in germ-free Drosophila.
- Define how F. nucleatum colonization enhances amphetamine-induced dopamine efflux in isolated fly brains and amphetamine-driven behaviors in adult Drosophila.
More about the research
Amphetamine makes DAT run in reverse, pushing dopamine out of the cell (dopamine efflux) and raising dopamine levels outside neurons. Blocking this efflux reduces amphetamine-driven movement and drug preference. There are no medicines to treat amphetamine misuse. The research asks, at the molecular level, what controls DAT reversal and how outside factors change it: partner proteins, membrane lipids, HIV proteins and gut bacteria. Much of the work uses fruit flies (Drosophila), whose isolated brains and behaviors serve as models for amphetamine actions.
Why it matters
No medications currently treat amphetamine use disorder. By mapping the protein and lipid contacts that let amphetamine reverse the dopamine transporter, this work could point to new ways to block dopamine efflux and curb amphetamine-driven behaviors. It may also explain why people with HIV, or with certain gut microbiome imbalances, are prone to heavier amphetamine use, which could inform care for these vulnerable groups.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Rebecca Hofford
Wake Forest University, NC·Neuroscience·Early-career
Test how depleting the gut microbiome in adolescent versus adult mice changes fentanyl self-administration, a measure of how strongly the drug reinforces drug-taking.
Ann Ragin
Northwestern University, IL·Neuroscience
Test whether dopamine transporter levels in the striatum, measured by SPECT/CT, are reduced in people with HIV and major depression, and whether they correlate with symptom severity and MRI brain alterations.
Crystal Archer
University of Arkansas, AR·Biophysics·Early-career
Solve the solution structure of the purified Kv7.2 C-terminal region, the channel's internal tail where helper molecules bind, using advanced 3D and 4D NMR spectroscopy.
The school
University of Alabama at Birmingham: 45 labs on PI Pages, $866M a year on research, 166 research doctorates a year.
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