Basic mechanisms of epileptogenesis
Until now, treatment of epilepsy has been limited to the suppression of seizures.
However, the holy grail of the epilepsy research community has been to find a cure
for epilepsy. Toward this end, the key questions that need to be answered are: (1)
How does normal brain become epileptic? and (2) Is it possible for epileptic brain
to "normalize?" These have been the areas of my basic research endeavors.
(1) We have shown that transient activation of group I metabotropic glutamate receptors
in the normal hippocampus elicits a persistent enhancement of excitability, producing
a protein synthesis-dependent epileptic state. One can envision this mechanism being
relevant to patients with head trauma or ischemic insults to the brain, in which massive
glutamate release during the insult may induce excessive group I mGluR activation
and result in the development of post-stroke or post-traumatic epilepsy. By examining
the necessary receptors, induction and maintenance mechanisms, and intracellular pathways
involved, we hope to discover the means to prevent epileptogenesis and suppress resistant
seizures in vulnerable patient populations (work done in collaboration with Bob Wong,
Peter Bergold, Michaelangelo Fuortes, Marjorie Rico and others).
(2) Pediatric neurologists have long known that patients with certain subtypes of
pediatric epilepsy outgrow their seizures in adolescence, suggesting there may be
a way to enhance remission of epilepsy. Dr. Smith, a colleague here at Downstate
and an expert in the field of developmental changes in expression of GABAA receptor subtypes, was the ideal collaborator for this investigation. Together, we
have discovered that enhanced expression of α4βδ GABAA receptors underlies the reduced seizure susceptibility of adolescent female mice
(work done in collaboration with Sheryl Smith, Lie Yang, and Hui Shen).
Other research by us and colleagues pertains to medical curriculum development and
educational reform (see publication list below).
- Member, American Academy of Neurology (AAN) Undergraduate Education Subcommittee (representative
of the Association of University Professors of Neurology)
- Member, AAN Clerkship Director Innovation Award Selection Committee
- Member, NIH study section ZRG1 RPHB-R, Small Business: Psycho/Neuropathology, Lifespan
Development, and STEM education
- Ad hoc reviewer of grants and manuscripts for various organizations and journals