The Laboratory of Epilepsy and Neurodevelopment

mTORopathies-related epilepsy: Focal cortical dysplasia type II (FCD II) is one of the most common pathology in patients with drug-resistant epilepsies. Using the combination of molecular genetics, electrophysiology, and human data, we aim to focus on defining the underlying genetic, cellular, and circuit mechanisms contributing to epileptogenesis, ictogenesis, and cortical hyperexcitability.  We ask the following questions:  

1. The temporospatial evolution of epileptogenesis and ictogenesis in the dysplastic brain. 

2. The logical molecular and cellular networks contributing to cell-autonomous and non-cell-autonomous epileptogenicity.

3. The mechanistic-based therapeutic development.  

Modeling mTORopathies-related epilepsie

Sudden unexpected death in epilepsy (SUDEP): Sudden unexpected death in epilepsy (SUDEP) accounts for up to 17% of deaths in patients with epilepsy, second only to stroke in potential life-years lost due to neurological diseases. The etiology of SUDEP is heterogeneous, including cardiac, respiratory, and autonomic dysregulation for different epilepsy syndromes. We ask the following questions:

Mice develop ictal apnea long before cardiac arrest during fatal seizures.

Animals with FCDII develop astrogliosis and microgliosis in nucleus tractus solitarius (NTS).

Infantile epileptic encephalopathies (IEE):  The advent of next-generation DNA sequencing has revolutionized gene discovery in human diseases, including epilepsy. Hundreds of genes have been implicated in epilepsy in the last decade, revealing the diversity of biological mechanisms that can go awry in this disorder. However, the rate at which we are identifying new genes involved in epilepsy is now vastly outpacing our ability to study disease mechanisms. Using transgenic mice, IUE-mediated somatic mutagenesis, and electrophysiology, we ask the following questions:

CRISPR-IUE mediated somatic mutagenesis to study the function of SPTAN1 in neurodevelopment

Synaptic and non-synaptic function of STXBP1 

 Mesial temporal lobe epilepsy  (mTLE): Hippocampal sclerosis is the most common pathology in adult patients with drug-resistant epilepsy. Although we have gained staggering advancement in our understanding of TLE, we have failed to develop disease-modifying therapies that target both epilepsy and epilepsy-related comorbidities. Using pilocarpine and intrahippocampal kainic acid TLE models, we ask the following questions: