Our research focus is to  understand the process of epileptogenesis and to identify novel therapies that reduce seizures and that improve the quality of life of children with epilepsy. The lab combines different technologies and approaches including genomics and functional studies. Learn more about our research and areas of study below.



We study gene expression in brain samples surgically resected from patients with focal epilepsy, from mice with a genetic mutation that causes severe epilepsy in children, and from neurons derived from human-induced pluripotent stem cells carrying the same mutation.


Our knock-in mouse model features a gain-of-function mutation at amino acid position 1768 in the Nav1.6 protein, substituting Asparagine (N) for Aspartic acid (D) (N1768D). This model allows us to understand epileptogenesis in a new light. Rather than the conventional chemical or mTBI induced epilepsy mouse model, we are now able to study pathophysiology before and after seizure onset. Current projects are understanding epileptogenesis in regard to:

  1.  sex differences through RNA-Seq coupled pathway analysis
  2. blood brain barrier dysfunction and its role in pathology
  3. testing novel therapeutics to prevent/delay the onset of seizures.


Our gene expression profiling studies have provided clues as to which biological pathways are altered in the lead up to seizures, and we are beginning functional studies to learn more about these key pathways, and possible ways to target them to prevent seizures.


In collaboration with Dr. Lalitha Madhavan, we have established a human pluripotent stem cell (iPSC) model with the SCN8A-N1768D variant to complement pathophysiological studies in the mouse, and to enhance therapeutic potential.

SCN8A Projects

Epilepsy afflicts approximately 750,000 children in the United States and ~45,000 children suffer severe forms beginning in infancy. Early infantile epileptic encephalopathies (EIEE) are a devastating form of epilepsy characterized by global developmental delays, motor and speech deficits, autism, and intractable seizures with a high risk of sudden death (SUDEP). Unfortunately, conventional and newer anti-epileptic drugs control the seizures of only a small percentage of children with EIEE. Mutations in a large set of genes have been implicated in the etiology of EIEE, several of which are in voltage gated ion channels.

In 2012, the Hammer lab discovered the first mutation (SCN8A-N1768D) in the sodium channel SCN8A (Nav1.6) in a patient with early onset intractable seizures, developmental delay, and SUDEP. There are now over 300 patients known worldwide with SCN8A-related epilepsy with encephalopathy, and thousands more with related sodium ion channelopathies.

In our lab, we employ a knock-in mouse carrying the N1768D (D/+) mutation to test therapeutic interventions in an animal model that is more representative of human epilepsy than current chemical-induced animal models. In collaboration with Dr. Lalitha Madhavan, we have established a human pluripotent stem cell (iPSC) line with the N1768D variant to complement pathophysiological studies in the mouse, and to enhance therapeutic potential.

Human TLE

In collaboration with Dr. Martin Weinand, we have studied alterations in gene expression in brain samples from patients with temporal lobe epilepsy (TLE). We performed RNA-seq on hippocampal tissue resected from 12 medically intractable TLE patients with pre-surgery seizure frequencies ranging from 0.33 to 120 seizures per month. We then performed differential expression (DE) analysis comparing a group patients with an average of 4 seizures per month (LSF) with a second group with an average of 60 seizures per month (HSF). A total of 979 genes with ≥2-fold change in transcript abundance distinguished these groups. When compared with post-mortem hippocampal controls, a total of 1,676 genes were found to be significantly downregulated in HSF patients compared with only 399 downregulated genes in LSF patients.

Pathway analysis revealed >50 significantly deactivated or activated signaling pathways, with Signal Transduction as the central hub in the pathway network. While neuroinflammation pathways were activated in both seizure frequency groups, the HSF group systematically deactivated several key signaling pathways, including calcium, CREB and Opioid signaling.

We also infer that increased expression of the immediate early gene, NPAS4, and a signaling cascade promoting synaptic scaling via AMPA receptors, may have played a key role in maintaining a higher seizure threshold in the LSF cohort. These results suggest that therapeutic approaches targeting synaptic scaling pathways may aid in the treatment of seizures in TLE

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