Rebecca Muhle
Columbia University, NY·Neuroscience
Mutations in a single gene can reshape brain development enough to produce autism, but tracing the path from the gene to the behavior requires knowing which cells and circuits it touches. CHD8, short for Chromodomain Helicase DNA-binding Protein 8, is among the most confidently established autism risk genes; it works by remodeling how DNA is packaged, thereby controlling which other genes switch on.
- Fields
Neuroscience
Genetics
Medicine & Clinical Research
- Topics
autism spectrum disorder
chromatin remodeling
neurodevelopmental disorders
- Grants
- 1 known grant, through Feb 2028
What they work on
- Map cellular, transcriptional and epigenetic changes in developing ventral midbrain and striatum of Chd8+/- mice using single-nucleus RNA sequencing and single-nucleus ATAC sequencing of chromatin accessibility.
- Determine how CHD8 loss disrupts transmission of the dopamine signal through the basal ganglia, using fiber photometry and in vivo extracellular recordings in constitutive and conditional haploinsufficiency models.
- Localize CHD8 DNA binding within defined cell types of the dopaminergic system by chromatin immunoprecipitation and sequencing of a conditionally biotinylated Chd8-tag transgene.
- Test whether genes dysregulated by CHD8 loss include other autism risk genes critical to basal ganglia and dopaminergic function.
More about the research
Prior work from this investigator showed that CHD8 in the developing cortex regulates other autism risk genes. Separately, converging evidence implicates the basal ganglia, brain structures governing movement, habit and reward, and especially their dopamine signaling, in core autism symptoms.
Why it matters
Autism spectrum disorder is a chronic neurodevelopmental condition carrying lifelong morbidity and increased mortality, and its core symptoms have no targeted biological treatment. Pinning down which cell types, circuits and gene networks go wrong when CHD8 is lost would close a specific gap in understanding autism biology and could inform later translational work aimed at the dopaminergic circuitry underlying repetitive and movement-related symptoms.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
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University of South Carolina-Columbia, SC·Neuroscience
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Howard Gritton
University of Illinois Urbana-Champaign, IL·Neuroscience
Test whether developmental phthalate exposure reduces anatomical and functional connectivity among frontal, sensory and limbic brain regions in mice, using whole-brain magnetic resonance imaging (MRI).
The school
Columbia University: 89 labs on PI Pages, $1.4B a year on research, 625 research doctorates a year.
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