Claes Wahlestedt
University of Miami, FL·Neuroscience
Most people who drink alcohol never become addicted. A minority, however, keep drinking despite harmful consequences or at the cost of other rewards, a pattern called compulsivity.
- Fields
Neuroscience
Genetics
Pharmacology
- Topics
alcohol addiction
alcohol use disorder
compulsivity
- Grants
- 1 known grant, through May 2027
What they work on
- Profile the silencing histone mark H3K27me3 in amygdala neurons and non-neuronal cells of rats that drink alcohol compulsively despite foot-shock, using CUT&RUN mapping, and link differences to gene expression with RNA sequencing.
- Test whether turning PRKCD-expressing inhibitory neurons in the amygdala up or down changes compulsive alcohol self-administration, using chemogenetics in a PRKCD-Cre transgenic rat.
- Define H3K27me3 levels and gene expression specifically in PRKCD neurons of compulsive rats, using a Cre-inducible nuclear tagging approach.
- Knock down the histone methyltransferase EZH2 only in amygdala PRKCD neurons to test its role in compulsive drinking with brain-region and cell-type specificity.
More about the research
Because this happens only in some individuals, vulnerability is thought to lie at the core of the disease. Epigenetics, the chemical marks that turn genes on or off without changing the DNA sequence, offers one explanation. These marks combine genetic risk with environmental influences such as stress and alcohol itself. The lab's previous work showed that addiction-related behavior changes arise from lasting epigenetic reprogramming of gene networks in specific brain regions and neuron types.
Why it matters
Alcohol addiction is a debilitating disorder with few effective treatments. Epigenetic enzymes such as EZH2 are increasingly seen as druggable targets for psychiatric disease. Showing how EZH2 reprograms specific amygdala neurons in compulsive drinking could point toward new therapeutic strategies for people with alcohol use disorder.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Leanne Holt
Temple University, PA·Neuroscience·Early-career
Rescue neuronal underactivity with DREADDs, engineered receptors that switch on chosen cells, while recording astrocyte calcium signals during cocaine self-administration in rodents.
Subhash Pandey
University of Illinois Chicago, IL·Neuroscience
Test whether EZH2, an enzyme that adds methyl tags to histones, controls synaptic genes, electrical activity, synapse structure and anxiety-like behavior in the central amygdala of male and female rats during alcohol withdrawal, and examine these genes in postmortem human AUD amygdala.
Yasmin L. Hurd
Icahn School of Medicine at Mount Sinai, NY·Neuroscience
Determine how prenatal cannabis or THC exposure disturbs immune-related genes in the placenta and brain, using placentas from women who used cannabis during pregnancy and rats exposed to THC during development.
The school
University of Miami: 30 labs on PI Pages, $559M a year on research, 297 research doctorates a year.
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