Innate and Adaptive Immunity in Childhood Epilepsy

The studies proposed in Dr. Koh’s application will use long-established expertise from the Miller lab for the analysis of CNS-resident and CNS-infiltrating populations of inflammatory cells involved in the pathogenesis of EAE. In addition, our lab also has long-established expertise in the use of appropriate transgenic and knockout mice as well as bone marrow chimeras to examine the roles of innate and adaptive immune responses in the pathogenesis of autoimmune and virus-induced CNS disease which are directly applicable to our proposed studies. Our lab thus has the intellectual and technical expertise to partner with Dr. Koh’s group to elucidate the functional roles of innate immune inflammation and adaptive immunity in priming the brain for later progression of epilepsy. Recent collaborative studies between the Koh and Miller labs have revealed activation of both CNS-resident as well as a significant contribution of CNS-infiltrating peripheral inflammatory lymphocytes, macrophages and dendritic cells in your epilepsy model which provide important rationale for your proposed approach to disease therapy in this model. I am willing to serve as a co-investigator, devoting 5% academic year effort, on this application. A postdoctoral fellow in my lab will devote 50% effort to these studies and will be primarily responsible for testing the hypothesis that immunologic responses to febrile convulsions cause heightened susceptibility to subsequent seizures (Aim 1), and to determine the role of innate and adaptive immunity in this early-life seizure model through the immune-related assays and flow cytometric analysis of CNS inflammatory cells (experiment 4 in Aim 2 and all experiments in Aim 3). We will also help members of the Koh laboratory in conducting the proposed studies. I will consult regularly with Dr. Koh to review data and plan experiments as well as meeting daily with the postdoc to discuss experimental design and results.