PIPages
Labs

Scott Adney

Northwestern University, IL·Neuroscience·Early-career

Many hard-to-control seizures in babies and young children trace back to a change in a single gene. Often that gene builds an ion channel, a pore that lets charged atoms flow in and out of nerve cells.

Fields

Neuroscience

Medicine & Clinical Research

Genetics

Topics

epilepsy

NaV1.2

voltage-gated sodium channel

Grants
1 known grant, through Apr 2027

What they work on

  1. 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.
  2. Test how the two variants change activity in elementary circuits of iPSC-derived neurons, to find the point where their distinct effects converge on an epileptic phenotype.
  3. Define changes in hippocampal excitability, synaptic signaling and network output in genome-edited mice carrying SCN2A-E430A, using ex vivo brain slice analysis.
  4. Relate circuit changes to seizures in living E430A mice using EEG and depth electrode recordings that track where and when abnormal brain activity occurs.

More about the research

SCN2A is one such gene. It encodes NaV1.2, a sodium channel that is abundant early in development in excitatory neurons, the cells that use the signaling molecule glutamate to switch on their neighbors. Variants that weaken the channel ('loss-of-function') are linked to autism and later-onset epilepsy. Variants that strengthen it ('gain-of-function') mostly cause epilepsy starting in infancy. Few disease models exist for the gain-of-function form, so it is still unclear how overactive excitatory neurons early in life lead to seizures.

Why it matters

Infantile-onset seizures caused by single ion-channel gene changes can be very difficult to control with current medications, and epilepsy can even lead to sudden death. By showing how gain-of-function SCN2A variants make neurons and circuits overactive, this work could point to new therapeutic approaches for children with SCN2A-related epilepsy.

Known grants

From NIH and NSF research grants. Labs often have other funding we can't see.

Multi-scale disease modeling of SCN2A-related epilepsy due to gain-of-function variants

NIH · Jul 2022 – Apr 2027

Closest labs

Yang Yang

Purdue University, IN·Neuroscience

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.

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.

Manu Ben Johny

Columbia University, NY·Biophysics

Determine whether CaV2.1 and CaV2.2 calcium channels are S-palmitoylated, carrying an attached lipid group, in central and peripheral neurons, and how this modification alters channel activity.

The school

Northwestern University: 71 labs on PI Pages, $1.3B a year on research, 536 research doctorates a year.

More about Northwestern University

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