Yang Yang
Purdue University, IN·Neuroscience
One gene, SCN2A, is among the leading genetic causes of autism and other neurodevelopmental disorders. It encodes Nav1.2, a voltage-gated sodium channel: a pore in the brain cell membrane that lets sodium in so neurons can fire electrical signals.
- Fields
Neuroscience
Genetics
Pharmacology
- Topics
Nav1.2
voltage-gated sodium channel
autism spectrum disorder
- Grants
- 3 known grants, through Jul 2027
What they work on
- Map how loss of Scn2a changes neurons in the medial prefrontal cortex, a social-behavior hub, using brain-slice patch-clamp recordings of synaptic excitation and inhibition plus Neuropixels high-density probes to record firing in behaving mice.
- Test whether shifting the excitation/inhibition balance in the mPFC microcircuit with optogenetics and chemogenetics, light- and drug-controlled neuronal switches, corrects social and other behavioral deficits in Scn2a-deficient mice.
- Determine the best timing for treatment by switching Scn2a expression back on, using the mouse model's built-in genetic rescue element, and by drug intervention at different ages.
- Test whether severe Scn2a deficiency causes neuronal hyperexcitability through downregulation of potassium channels, combining ex vivo excitability recordings with in vivo firing measurements and seizure-susceptibility testing.
- Build a Dual-AAV gene replacement system that splits the oversized SCN2A gene across two viral vectors and reassembles full-length Nav1.2 channel protein inside cells.
- Ask whether Dual-AAV delivery of normal SCN2A rescues behavior in Scn2a-deficient mice and cellular phenotypes in 3D brain organoids grown from human induced pluripotent stem cells carrying protein-truncating SCN2A variants.
More about the research
Many patients carry mutations that reduce the amount of working channel, a state called SCN2A deficiency, and there is no effective treatment. Work here asks what goes wrong in brain cells and circuits when this channel is scarce, how that produces social and behavioral problems and seizures, and whether restoring the gene can reverse those problems. The projects share a mouse model made by a "gene trap" strategy, in which the Scn2a gene is interrupted but carries a built-in element that lets expression be switched back on, plus human stem-cell models.
Why it matters
SCN2A deficiency is one of the most common single-gene causes of autism, and about 30% of affected children also have hard-to-treat seizures. Mapping how the missing sodium channel changes neuron firing and circuit activity could identify drug targets for those seizures and social deficits. The Dual-AAV approach, if it works, may also offer a route to gene replacement for other neurological disorders caused by genes too large for a single viral vector.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Scott Adney
Northwestern University, IL·Neuroscience·Early-career
Determine how the SCN2A gain-of-function variants M1879T and E430A each make neurons more excitable through different biophysical mechanisms, by recording from patient-derived iPSC neurons.
Richard S Smith
Northwestern University, IL·Neuroscience·Early-career
Define the prenatal onset and cellular basis of disease caused by novel SCN2A sodium channel variants, using transient transgenic ferrets, whose folded neocortex resembles the human brain, to assess effects on cell proliferation, cell fate, and neuronal migration.
Sergiu Pasca
Stanford University, CA·Neuroscience
Generate and functionally characterize human stem cell-derived organoids that resemble the spinal cord floor plate, the midline structure that guides crossing axons.
The school
Purdue University: 43 labs on PI Pages, $932M a year on research, 833 research doctorates a year.
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