Leanne Holt
Temple University, PA·Neuroscience·Early-career
Addiction leaves long-lasting changes in which genes are switched on across the brain's reward circuits. Most research has focused on neurons, but astrocytes, star-shaped support cells in the brain, also appear to influence how animals respond to cocaine.
- Fields
Neuroscience
Genetics
Pharmacology
- Topics
addiction
substance use disorder
cocaine
- Grants
- 1 known grant, through Nov 2029
What they work on
- Rescue neuronal underactivity with DREADDs, engineered receptors that switch on chosen cells, while recording astrocyte calcium signals during cocaine self-administration in rodents.
- Identify sex-specific astrocyte genes marked by the silencing histone mark H3K27me3 by comparing CUT&RUN and RNA sequencing data with bioinformatics.
- Test how astrocytic epigenetic regulation contributes to cocaine drug-seeking by using a virus to alter the H3K27me3-removing enzyme Kdm6a/UTX in astrocytes.
More about the research
No one has yet mapped how astrocytes' overall gene activity changes after drug exposure, or what controls those changes. This project asks how gene regulation in astrocytes supports cocaine drug-seeking.
Why it matters
Cocaine use disorder carries a heavy healthcare burden, and current understanding centers on neurons. Showing how astrocytes reshape their gene activity to support drug-seeking could reveal new cell types and molecular regulators, such as the enzyme Kdm6a/UTX, as potential targets for addiction treatment.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Claes Wahlestedt
University of Miami, FL·Neuroscience
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.
Eric J. Nestler
Icahn School of Medicine at Mount Sinai, NY·Neuroscience
Identify stable "chromatin scars" left in the mouse nucleus accumbens by early life stress, using unbiased proteomic and next-generation sequencing screens in specific neuron types and keeping only marks also found in postmortem accumbens from depressed humans.
Jonathan Hommel
University of Texas Medical Branch at Galveston, TX·Neuroscience
Test whether a GABA pathway running from the dorsal raphe nucleus to the nucleus accumbens converges on the ventral pallidum, a reward and motivation center, to control cocaine taking, using transsynaptic tracing to map connections between neurons.
The school
Temple University: 22 labs on PI Pages, $315M a year on research, 238 research doctorates a year.
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