Faculty Member
Assistant Professor in Residence
Department of Neurology
David Geffen School of Medicine
University of California, Los Angeles
Personal Statement
My lab aims to advance epilepsy treatment by understanding the epileptogenic processes that lead to recurrent seizures and cognitive dysfunction. I began studying the hippocampus as a graduate student, examining the post-transcriptional mechanisms of synaptic plasticity in primary neuronal and glial co-cultures. I continue to investigate the mechanisms of plasticity in the adult hippocampus, now in the pathological context of epileptogenesis in mouse models of epilepsy. As an epileptologist, I am privileged to participate in the care of Veterans with medication refractory epilepsy. Despite the expanding repertoire of treatments for seizures, we still lack therapies to prevent or cure epileptogenesis. Additionally, many epilepsy patients are also burdened with comorbid cognitive impairment, for which there are no treatments. These unmet needs are the primary motivation that guides my lab’s preclinical experimentation.
To elucidate the mechanisms underlying epileptogenesis, we have used single cell sequencing to profile cell type specific transcriptomic changes in the pilocarpine model of temporal lobe epilepsy. Many of our sequencing findings are concordant with existing literature on changes that occur during epileptogenesis, and have also generated several novel hypotheses for further exploration. One of the revelations from the data is the transcriptomically distinct population of microglia that are abundant in epileptic hippocampi, which we call epilepsy-associated microglia (EAM). The EAM share several genes with disease-associated microglia in other neurological disorders with increased risk for epilepsy, including Alzheimer’s disease and traumatic brain injury.
Our follow-up studies with immunostaining and electron microscopy indicate that EAM have an “activated” phenotype. Experiments to dissect the pro- and anti-epileptogenic potential of these microglia will be pursued in the proposed studies.
