Explore This Lab

Overview

Our long-term research goal is the development of new approaches to the treatment of epilepsy based on a clearer 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 our recent discovery that reversed ion transport in the immature brain was blocking the effects of the anticonvulsants most commonly used to treat neonatal seizures, and that a safe and well-characterized diuretic could ameliorate this condition.

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. We have found evidence for reentrant or circular patterns of neural activity that resemble cardiac fibrillation and precede seizures. We are currently testing whether this reentrant activation of neural circuits is the earliest stage of a seizure, and the stage at which intervention is most effective. We are also testing whether long-term reductions in the strength of synaptic connections between neurons in epileptic networks can reduce the probability of seizures.

Research Projects

Cortical Seizures in Newborn Infants

Seizure activity in the cerebral cortex of the brain (represented by the white electrographic discharges in the illustration) is transmitted through subcortical brain regions to the muscles of the body, causing convulsions. However, cortical seizures in newborns are frequently observed on electrographic recordings without accompanying convulsions, a dissociation that is exacerbated by anticonvulsant treatment. Most newborn convulsions are treated with anticonvulsant drugs that enhance the activity of GABA, a neurotransmitter that inhibits neuronal activity and seizures by increasing the flow of chloride ions into neurons.

DClamp - Free data acquisition and analysis software for epilepsy animal research.

The main goal of this project is to provide free, open-source data acquisition and analysis software to the epilepsy research community. Our goal is to establish a common platform to facilitate data exchange and cooperation between research centers. DClamp is designed for unsupervised detection of ictal-like and inter-ictal-like events in very large EEG datasets, for example from days to months of continuous recordings. It includes algorithms for automatic detection, quantification, and analysis of seizures (White et al. J Neurosci Methods, 15;152:255-66, 2006) and interictal spikes (Dyhrfjeld-Johnsen et al. J Clin Neurophysiol 27:418-24, 2010; White et al. Epilepsia 51:371-83, 2010).

Currently DClamp can also be used for acquisition of in vivo and in vitro signals from as many as 64 separate channels or animals. Examples include chronic EEG data, ECoG data, extracellular field potentials, intracellular potentials, intracellular currents (using low cost acquisition cards). We plan to expand compatible hardware. Future expansions will include synchronization of signal recordings with surveillance videos. Project will be distributed as open source allowing users to modify the code.

Chloride Concentrations and GABA Signaling in Nonconvulsive Seizures

Using a genetically expressed chloride sensor and multiphoton microscopy, we show in this paper that cortical neurons in the developing mammalian brain have much higher chloride concentrations than do subcortical neurons (in the illustration, hotter colors represent higher chloride concentrations). These differences in chloride concentration lead to oppositely directed chloride flow, GABA signaling, and anticonvulsant effects in these two regions. The response of cortical neurons to GABA could be made to match the subcortical response by blocking the transporter that accumulates chloride in cortical neurons. Under these conditions, cortical seizure activity could be controlled as readily as subcortical seizure activity.

These differences provide the first candidate explanation for the puzzling dissociation of convulsions and electrographic seizure activity in newborns, the exacerbation of the dissociation by anticonvulsants, and the potential utility of blocking chloride transporters to improve control of nonconvulsive seizures in newborns.

Research Positions

Please contact Dr. Kevin Staley at Staley.Kevin@mgh.harvard.edu if you are interested in working in the lab.

Read about and apply for residency, fellowship and observership programs in neurology.

We are now accepting applications for 2020 student interns.

Publications

Visit PubMed for a complete list of publications. Below is a selection of recent materials:

Mannitol decreases neocortical epileptiform activity during early brain development via cotransport of chloride and water. Glykys J, Duquette E, Rahmati N, Duquette K, Staley KJ. Neurobiol Dis. 2019 May;125:163-175. doi: 10.1016/j.nbd.2019.01.024. Epub 2019 Feb 1. PMID: 30711483

Optogenetic dissection of ictogenesis: in search of a targeted anti-epileptic therapy. Lillis KP, Staley KJ. J Neural Eng. 2018 Aug;15(4):041001. doi: 10.1088/1741-2552/aab66a. Epub 2018 Mar 14. PMID: 29536948

Epileptiform activity in traumatic brain injury predicts post-traumatic epilepsy. Kim JA, Boyle EJ, Wu AC, Cole AJ, Staley KJ, Zafar S, Cash SS, Westover MB Ann Neurol. 2018 Apr;83(4):858-862. doi: 10.1002/ana.25211. Epub 2018 Apr 10 PMID:29537656

Optogenetic dissection of ictogenesis: in search of a targeted anti-epileptic therapy. Lillis KP, Staley KJ. J Neural Eng. 2018 Mar 14. doi: 10.1088/1741-2552/aab66a. [Epub ahead of print] PMID:29536948

Epileptiform activity in traumatic brain injury predicts post-traumatic epilepsy. Kim JA, Boyle E, Wu AC, Cole AJ, Staley KJ, Zafar S, Cash SS, Westover MB. Ann Neurol. 2018 Mar 14. doi: 10.1002/ana.25211. [Epub ahead of print] PMID:29537656

Chloride Dysregulation, Seizures, and Cerebral Edema: A Relationship with Therapeutic Potential. Glykys J, Dzhala V, Egawa K, Kahle KT, Delpire E, Staley K. Trends Neurosci. 2017 May; 40(5):276-294. PMID: 28431741.

Epileptogenesis in organotypic hippocampal cultures has limited dependence on culture medium composition. Liu J, Saponjian Y, Mahoney MM, Staley KJ, Berdichevsky Y. PLoS One. 2017 Feb 22;12(2):e0172677


Research Scientists

  • Fatemeh Bahari, PhD, Research Fellow
  • Trevor Balena, PhD, Research Staff
  • Volodymyr Dzhala, PhD, Instructor in Neurology
  • Lauren Lau PhD, Research Fellow
  • Kyle Lillis, PhD, Instructor in Neurology
  • Kieran Normoyle MD, PhD, Research Fellow
  • Negah Rahmati PhD, Research Fellow

Research Assistants & Technicians

  • Hannah Lynch, Research Tech I
  • Michelle Mail, Technologist II
  • Patti Staley, Staff Assistant II
  • Rehan Raiyyani, Research Tech II

Affiliated Lab Members

  • Catherine Chu, MD, Assistant Professor in Neurology, Mass General, K23 Grantee
  • Albert Misko MD, PhD, Instructor in Neurology, Mass General, K12 Grantee

Student Interns

  • Britney Pitter, Morehouse School of Medicine, Atlanta, GA
Accepting applications for 2020
Alumni

Research Assistants & Technicians

Name Current Position Location
Tom Jasionowski Medical Scribe Oregon Urology Institute, Eugene, Oregon
Samantha Kumarasena Medical Student Tufts University School of Medicine, Boston, MA, MD 2021
Kimberly Lu Medical Student Boston University School of Medicine, MA
Yero Saponjian Life Science Strategy Consultant Boston, MA
Brittany Van Nelson, MPH Manager, Patient Recruitment  Engage Therapeutics, New Jersey/New York
Elizabeth Duquette Medical Student Georgetown University School of Medicine, MD 2026

Research Fellows

Name Current Position Location
Joseph Glykys MD, PhD Assistant Professor Univ. of Iowa, Children’s Hospital & Univ. of Iowa Neuroscience Center
Thomas Blauwblomme MD, PhD Physician-Scientist, Department of Pediatric Neurosurgery Hospital Necker, Paris, France
Yevgeny Berdichevsky PhD Associate Professor, Electrical & Computer Engineering Lehigh University, Bethlehem, PA
Jonas Dyhrfjeld-Johnsen PhD VP of Research & Translational Development, Sensorion Company Montpellier, France
Kiyoshi Egawa MD, PhD Clinical Fellow, Pediatric Department Hokkaido University School of Medicine, Japan
Chris French MPDS, FRACP, PhD Senior Neurologist & Epileptologist Royal Melbourne Hospital, Melbourne, Australia
Michael Gutnick DVM, PhD (Sabbatical) Koret School of Veterinarian Medicine, Jerusalem, Israel
Arash Hadipour-Niktarash MD Assistant Professor of Neurology University of Colorado, Denver
Jennifer Hellier PhD Assistant Professor in Family Medicine and Cell & Developmental Biology University of Colorado, Denver
Theju Jacob PhD Scientist, Bayer Corporation Research Triangle Park, NC
Sofia Karamintziou PhD Visiting Postdoctoral Fellow T. Georgiou PhD Lab, UC Irvine, CA
Sonya Kee Yun Jakawich PhD Strategy Consulting Blue Print Research Group, NY
Kristopher Kahle MD, PhD Assistant Professor of Neurosurgery & Pediatrics Yale School of Medicine, CT
Ji Lee MD, PhD Assistant Professor in Child Neurology & Neuro-immunology Columbia University, NY
Kyung-IL Park MD, PhD Assistant Professor in Neurology Seoul Paik Hospital, Inje University, South Korea
Jon Moussally MD Instructor in Emergency Medicine North Shore Medical Center, Salem, MA
Helen Consiglio PhD Assistant Professor & Program Director of Psychology Regis College, Weston, MA
Waldemar Swiercz PhD Research Scientist Amazon, Reading, MA
Zemin Wang MD, PhD Instructor in Neurology Brigham and Women’s Hospital, Boston, MA

Student Interns

Name School Current Position
Megan Audette SUNY Upstate Medical University, Syracuse, NY MD-2021
Nolan Wu Trinity University, San Antonio, TX Bachelors-2021
Larry Chen Albert Einstein Medical School, NY MD-2022
Julia Fong University of Sydney Medical School, Australia MD PhD
Tom Jasionowski Tufts University, Boston, MA Medical Scribe, Eugene, Oregon
Kimberly Lu University of Chicago Medical Center MD PhD, Medical Resident-Internal Medicine, 1st year
Humzah Mahmood Boston University, Boston, MA BSc-2016, Biomedical Engineering
Camila Cabarello MIT, Cambridge, MA PhD Student-2023, CANDLab, Yale University
Yun Xiang Chu Harvard Med. School, Boston, MA MD PhD Student, HMS-5th year
Elon Gaffin-Cahn Union College, Schenectady, NY PhD Student, Psychology, NYU
Hillary Mullan Oberlin College, Oberlin, OH UMass Medical School, MD-2020
William Neylon Dublin Institute of Technology, IRE University Hospital, Limerick, IRE
Rory Tinker University of Manchester Medical School, UK MD, BSc, 2020
Britney Pitter Morehouse School of Medicine, Atlanta GA MD 2022