Amy Lasek
Virginia Commonwealth University, VA·Neuroscience
Heavy, repeated drinking reshapes which genes brain cells switch on, and those changes can push someone further toward alcohol use disorder (AUD). Two projects ask how this gene regulation works and whether it can be interrupted.
- Fields
Neuroscience
Pharmacology
Genetics
- Topics
alcohol use disorder
binge drinking
drinking in the dark
- Grants
- 2 known grants, through May 2030
What they work on
- Map alcohol-induced changes in the cortical extracellular matrix, or "matrisome," using quantitative proteomics and glycomics in mice after six weeks of binge-like drinking in the dark, and compare them with transcriptome datasets.
- Test whether STAT3, an immune-related transcription factor, acts in astrocytes to drive drinking, by deleting Stat3 with floxed mice and the Aldh1l1-CreERT2 astrocyte Cre line and mapping STAT3 binding sites by ChIP-Seq.
- Determine whether brevican, a matrix protein surrounding synapses that regulates plasticity, controls alcohol intake, using astrocyte knockout and viral shRNA in prefrontal cortex plus super-resolution imaging of synaptic markers.
- Identify the genome-wide binding sites of the chromatin remodeling subunits SMARCA2 and SMARCA4 in ventral hippocampus before and after chronic binge drinking, using CUT&RUN sequencing integrated with single-nuclei RNA sequencing.
- Test the roles of SMARCA2 and SMARCA4 in ethanol consumption, locomotor activation, anxiety reduction and sedation tolerance, using dual small-molecule inhibitors and Cre-dependent viral knockout in the ventral hippocampus.
More about the research
One focuses on the extracellular matrix, the scaffolding of proteins and sugars that surrounds brain cells and helps hold synapses, the connections between neurons, in place. The other focuses on chromatin remodeling, the machinery that opens or closes stretches of DNA so transcription factors can reach their targets. Both use mice that drink alcohol in binge-like patterns, pair genome-wide measurements with targeted gene knockouts, and test effects on how much animals drink.
Why it matters
Alcohol use disorder has few effective medications. These projects aim to pin down specific molecules, the astrocyte transcription factor STAT3, the synapse-surrounding protein brevican, and the chromatin remodeling enzymes SMARCA2 and SMARCA4, that shape how much animals drink. Each could become a target for new drugs to reduce excessive alcohol consumption, and inhibitors of SMARCA2/SMARCA4 already exist as chemical tools.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Hyung Nam
Louisiana State University Health Sciences Center-Shreveport, LA·Neuroscience
Determine how chronic alcohol lowers neurogranin, a synaptic protein that tunes glutamate signaling, in the mouse medial prefrontal cortex, and test tolerance in mice with mPFC-specific Ng knockout or overexpression.
Samuel Centanni
Wake Forest University, NC·Neuroscience
Test whether stress-driven activity in the insula-BNST pathway predicts later binge and aversion-resistant ethanol drinking, following mouse models of stress and binge drinking over time.
Erbo Dong
Ohio State University, OH·Neuroscience
Determine whether PP1a, an enzyme that promotes HDAC4 build-up in the nucleus, drives the ethanol preference, tolerance and anxiety-like behavior seen in adult mouse offspring of prenatally stressed mothers.
The school
Virginia Commonwealth University: 19 labs on PI Pages, $524M a year on research, 438 research doctorates a year.
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