Our research focuses on epilepsy, neuroplasticity, and stem cell replacement therapy for temporal lobe epilepsy.
We are studying the cellular and molecular properties of mouse embryonic GABAergic progenitors in comparison to GABAergic progenitors derived from murine and human embryonic pluripotent stem cells (PSCs). The high motility and plasticity of GABAergic interneuron progenitors enables them to migrate extensively into mature brain circuits and rewire neural circuitry after they are transplanted into the dentate gyrus. We discovered that GABAergic progenitors from mouse PSCs mature and synaptically integrate into the adult hippocampus of mice (in collaboration with the labs of Laura Grabel and Gloster Aaron). We have also shown that embryonic GABAergic progenitor transplants suppress spontaneous seizures in the mouse pilocarpine model of temporal lobe epilepsy (TLE; done in collaboration with the labs of Gloster Aaron and Yuchio Yanagawa).
Our studies utilize a range of approaches to interrogate the synaptic integration of transplanted cells including electrophysiology and optogenetics, retroviral labeling, and continuous 24/7 video-electroencephalographic recordings. We routinely assess neurodegenerative changes and axonal sprouting using a range of histological and immunohistochemical approaches. Our well-equipped behavioral core and expertise in mouse behavioral testing enables us to examine spatial memory deficits, anxiety, depression, and sociability in mice to evaluate efficacy of stem cell therapies.
We have expertise in multiple epilepsy models in mice, including the audiogenic, kainic acid, pilocarpine models. Separate collaborative studies are focused on screening novel compounds for their ability to suppress seizures in the pilocarpine and and tuberous sclerosis models (in collaboration with the labs of Paul Lombroso and Angelique Bordey).