MGH Pediatric Epilepsy Research Lab

Overview

We seek new approaches to the treatment of epilepsy based on a better understanding of the necessary steps in seizure initiation and propagation.

The two major themes in the lab are neuronal ion transport and the spread of activity in neural networks. Neuronal ion transport underlies signaling at all fast synapses. The importance of neuronal ion transport was underscored by Volodymyr Dzhala’s discovery that reversed ion transport in the immature brain could block the effects of the anticonvulsants most commonly used to treat neonatal seizures, and that a safe and well-characterized diuretic could ameliorate this condition.  This work went from bench to bedside with the publication of the successful phase I-II trial of bumetanide as adjunctive therapy for neonatal seizures.

Kieran Normoyle is expanding this work by exploring the spatial distribution of the ions that are responsible for inhibitory membrane currents in neurons. He has found that microscopic pockets of unique concentrations of these ions impart unique characteristics to each inhibitory synapse.

Our work on the spread of excitation in neural networks combines fluorescent imaging of network activity with computerized analysis and modeling to understand how normal and abnormal signaling progresses through neural networks. Kyle Lillis has developed techniques to study the onset of spontaneous seizures in brain explants that are maintained for many weeks in culture.  This provides a unique opportunity to study seizure onset in a preparation in which the inputs and activities of all cells can be visualized.  Using this preparation Kyle and Theju Jacob found evidence that seizures develop from reentrant or circular patterns of neural activity that resemble cardiac fibrillation.  Lauren Lau found that these patterns do not originate from a particular group of “grandfather” neurons.  Rather the activity can begin in many different neurons and then spread to distant regions of the network.

Research Projects

• Trevor Balena studies how we know when injured neurons have died. He is using new transgenic fluorescent proteins to re-examine what we thought we knew about neurotoxic and neuroprotective conditions in the brain.
• Kieran Normoyle is studying the subcellular and extracellular distribution of chloride ions in the brain.
• Melanie McNally is studying the effects of mild hypoxic ischemic injury in the neonatal brain. This is a new frontier in neonatal medicine, and Melanie has developed new experimental techniques to determine when and how these mild injuries become manifest in the developing brain.
• Kyle Lillis is studying how the connectivity of individual neurons affects their role in the initiation of seizure activity. This work provides an alternative to the clinical practice of identifying the earliest-firing neurons as those with the most influence on seizure initiation.
• Lauren Lau is studying seizure onset using in vivo microscopy of neural networks whose activity is reported by transgenic fluorescent proteins.
• Volodymyr Dzhala is studying the transport of ions across the blood brain barrier and the effects of transport enhancers and inhibitors on the initiation of seizures in the injured neonatal brain.

Publications

View publications

Open Positions

Applications for Summer Student Lab Internships are accepted January-March each year. Email Dr. Staley: staley.kevin@mgh.harvard.edu