Richard S Smith
Northwestern University, IL·Neuroscience·Early-career
Before birth, the human brain is already electrically active, and those early electrical patterns help guide how the cortex is built. Ion channels, the pores that let charged ions cross a neuron's membrane and generate electrical signals, are therefore central to brain construction as well as to brain function later on.
- Fields
Neuroscience
Biomedical Engineering
Genetics
- Topics
voltage-gated sodium channels
ion channelopathy
malformations of cortical development
- Grants
- 2 known grants, through Jul 2030
What they work on
- 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.
- Determine the postnatal consequences of severe SCN2A variants on cortical structure and action potential kinetics in transgenic ferrets, testing whether the degree of gain-of-function sodium influx produces dose-dependent effects at different developmental stages.
- Design antisense oligonucleotide cocktails computationally, using machine learning simulations of neuronal activity, to modulate excitotoxicity pathways and stabilize electrical activity in specific neuronal cell types.
- Screen candidate RNA therapeutics across more than 100,000 human cerebral organoids on a high-throughput three-dimensional neurophysiology platform, reading out activity with paired calcium and voltage indicators.
More about the research
When they malfunction, the result can be a malformation of cortical development, a mis-built cortex that leads to epilepsy and severe disability in children. Two linked efforts here ask when during development these problems begin, and whether RNA-based drugs can stabilize a developing brain's electrical activity before damage becomes permanent.
Why it matters
Children with ion channel-driven cortical malformations and severe epilepsies have few effective treatments, and diagnosis typically comes after birth, once brain changes may already be irreversible. Mapping when sodium channel pathology starts could identify a window for intervention, while an off-the-shelf antisense oligonucleotide approach could make RNA precision medicine faster and far less costly than the current one-child-at-a-time model, extending it to patients in low-resource settings.
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.
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.
Gemma Carvill
Northwestern University, IL·Genetics
Identify the RNA-binding proteins that cause extra splicing-in of an SCN1A poison exon in people with epilepsy, using splice reporters and proteomics, and test whether antisense oligonucleotides correct it in patient iPSC-derived neurons.
The school
Northwestern University: 71 labs on PI Pages, $1.3B a year on research, 536 research doctorates a year.
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