Overview

I am particularly interested in treatment-resistant (refractory) forms of pediatric epilepsy since these often have a profound impact on the development of the child and impose a tremendous burden on families. One example of a pediatric epilepsy that we are working on is Dravet syndrome (DS) which is caused by loss-of-function mutations in the voltage-gated sodium channel SCN1A. DS is characterized by prolonged and complex febrile seizures (i.e. seizures due to high fever) that begin within the first 6 months of life and the subsequent development of refractory and severe afebrile seizures. Children with DS typically exhibit moderate to severe intellectual disability, a range of behavioral abnormalities, and a 15-20% mortality rate. Much of our research is focused on elucidating the mechanisms that underlie childhood epilepsies such as DS, with the long-term objective of using this information to develop treatments to reduce seizure frequency and ameliorate the neuropsychiatric comorbidities associated with epilepsy. Some of our areas of research are briefly described below.
1. Identification of novel epilepsy genes and mutations
The identification of epilepsy genes and mutations is an active area of research in my lab. The results from this gene discovery project are leading to the development of new hypotheses and research avenues. We are currently conducting functional studies on interesting novel mutations that are being identified in the known epilepsy genes. We are also engaged in extensive analyses to prove the pathogenicity of candidate disease mutations in novel genes.
2. Understanding the mechanisms of seizure generation
The overarching goal of our research is to develop more efficacious epilepsy treatments through a better understanding of the mechanisms of seizure generation. Towards this goal, we are generating and characterizing transgenic, knock-in/knock-out, and conditional knockout mouse models of human epilepsy. We freely provide our mice to other investigators. We use a wide variety of specialized techniques in the analysis of our mouse lines, including chemical and electrical methods of seizure induction, behavioral analyses, and long-term video/EEG analysis.
3. Understanding the cognitive and neuropsychiatric comorbidities in epilepsy
Children with severe forms of epilepsy often display intellectual disability and a range of clinically challenging neuropsychiatric comorbidities. We have expertise with a number of mouse behavioral assays and we are actively using our mouse models to identify and better understand the spectrum of cognitive and behavioral abnormalities that are associated with mutations in specific epilepsy genes. We are also interested in neuropsychiatric disorders such as schizophrenia which share mechanistic similarities with epilepsy.
4. Development of novel treatments for refractory epilepsy
The ultimate goal of the research in my lab is to facilitate the development of more efficacious treatments for patients with epilepsy. Since it is unlikely that there will be a silver bullet for the treatment of epilepsy, we are taking a multipronged approach in which we evaluate both established and novel therapeutics in our mouse models.

Academic Appointment

• Professor, Department of Human Genetics, Emory University
• Associate Professor, Emory University

Education

Research