Pediatric Epilepsy Research Lab: Kevin J. Staley, MD
Pediatric Epilepsy Research Lab
Mass General Building 114
16th Street, Room 2600
Charlestown, MA 02129
Kevin J. Staley, MD: email@example.com
Patient Appointments & Clinical Office
55 Fruit Street
Boston, MA 02114
Explore This Lab
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. This work has recently gone from bench to bedside with the completion and publication of the successful phase I-II trial of bumetanide as adjunctive therapy for neonatal seizures.
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. In collaboration with Kyle Lillis, we have developed techniques to study the onset of spontaneous seizures in brain explants that are maintained for many weeks. This provides a unique opportunity to study seizure onset in a preparation in which all cells can be studies, and all inputs are known. Using this preparation we found evidence for reentrant or circular patterns of neural activity that resemble cardiac fibrillation and precede seizures. 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.
Seizures and cerebral edema after brain injury
Seizures triggered by acute brain injury are poorly responsive to current therapies. Understanding how injury shifts ions and water in the brain can advance the treatment of acute seizures and cerebral edema. These two conditions lead to a great deal of morbidity, but without a clear understanding of the pathophysiology, more effective treatments cannot be developed. We have developed preparations and imaging technologies to help visualize the movement of ions after acute brain injury, leading the way to studies to identify effective therapeutic strategies. In one of these projects, Volodymyr Dzhala is seeking ways to increase the efficacy of bumetanide for the treatment of neonatal seizures.
Understanding interictal to ictal transitions
One of the most debilitating aspects of epilepsy is the unpredictable onset of seizure activity. If we understood how seizures start, or ictogenesis, we might be able to predict and prevent seizures more effectively. In long-term microscopic studies of in vitro and in vivo preparations, Kyle Lillis is tracking the activity of individual neurons to better understand how they come to participate in seizure activity. Many of the findings run counter to canonical ideas regarding the onset of seizures.
Neuronal death after brain injury
After brain injury, the normal mechanisms of neuronal death and removal are overwhelmed by the large numbers of neurons that have been fatally injured. Understanding how these mechanisms are altered provides a powerful and unique opportunity to improve the translation of studies of neuroprotection and neurotoxicity to clinical care.
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 2022 student interns, pending COVID status.
Visit PubMed for a complete list of publications. Below is a selection of recent materials:
In vitro ictogenesis is stochastic at the single neuron level. Lau LA, Staley KJ, Lillis KP. Brain. 2021 Aug 25:awab312. doi: 10.1093/brain/awab312.
Featured as a Top Ten article, Journal of Neuroscience 2021 Spotlight: Unique Actions of GABA Arising from Cytoplasmic Chloride Microdomains. Rahmati N, Normoyle KP, Glykys J, Dzhala VI, Lillis KP, Kahle KT, Raiyyani R, Jacob T, Staley KJ. J Neurosci. 2021 Jun 9;41(23):4957-4975. doi: 10.1523/JNEUROSCI.3175-20.2021.
KCC2 Chloride Transport Contributes to the Termination of Ictal Epileptiform Activity. Dzhala VI, Staley KJ. eNeuro. 2021 Mar 9;8(2):ENEURO.0208-20.2020. doi: 10.1523/ENEURO.0208-20.2020.
A perfect storm: The distribution of tissue damage depends on seizure duration, hemorrhage, and developmental stage in a gyrencephalic, multi-factorial, severe traumatic brain injury model. Costine-Bartell B, Price G, Shen J, McGuone D, Staley K, Duhaime AC. Neurobiol Dis. 2021 Jul;154:105334. doi: 10.1016/j.nbd.2021.105334.
Boston Bumetanide Trial Group. A Pilot Randomized, Controlled, Double-Blind Trial of Bumetanide to Treat Neonatal Seizures. Soul JS, Bergin AM, Stopp C, Hayes B, Singh A, Fortuno CR, O'Reilly D, Krishnamoorthy K, Jensen FE, Rofeberg V, Dong M, Vinks AA, Wypij D, Staley KJ; Ann Neurol. 2021 Feb;89(2):327-340. doi: 10.1002/ana.25959.
A Proposed Mechanism for Spontaneous Transitions between Interictal and Ictal Activity. Jacob T, Lillis KP, Wang Z, Swiercz W, Rahmati N, Staley KJ.J Neurosci. 2019 Jan 16;39(3):557-575. doi: 10.1523/JNEUROSCI.0719-17.2018.
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.
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.
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.
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.
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.
Chloride Dysregulation, Seizures, and Cerebral Edema: A Relationship with Therapeutic Potential. Glykys J, Dzhala V, Egawa K, Kahle KT, Delpire E, Staley KJ. Trends Neurosci. 2017 May; 40(5):276-294. doi: 10.1016/j.tins.2017.03.006.
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. doi: 10.1371/journal.pone.0172677.
Our Research Team
- Unit Chief, Pediatric Neurology
- Fatemeh Bahari, PhD, Research Fellow
- Trevor Balena, PhD, Research Staff
- Volodymyr Dzhala, PhD, Instructor in Neurology
- Lauren Lau PhD, Research Fellow
- Kyle Lillis, PhD, Assistant Professor
- Melanie McNally MD, Instructor in Neurology
- Kieran Normoyle MD, PhD, Research Fellow
Research Assistants & Technicians
- Michelle Mail, Technologist II
- Patti Staley, Staff Assistant II
- Rehan Raiyyani, Research Tech II
Affiliated Lab Members
- Beth Bartell PhD, Assistant Professor, Neurosurgery, Mass General Hospital
- Catherine Chu, MD, Assistant Professor in Neurology, Mass General, K23 Grantee
Student InternsAccepting applications for 2022, pending COVID status
Research Assistants & Technicians
|Tom Jasionowski||Medical Scribe||Oregon Urology Institute, Eugene, Oregon|
|Samantha Kumarasena||Resident Physician||
Beth Israel-Deaconess Medical Center, Boston, MA
|Kimberly Lu||Physician||University of Chicago Hospital, Chicago, IL|
|Hannah Lynch||Medical Student||
New York Institute of Technology, College of Osteopathic Medicine, MD 2024
|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|
|Negah Rahmati PhD||Research Scientist||Sage Therapeutics, Cambridge, MA|
|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||CDO, Acousia Therapeutics||Tubingen, Germany|
|Kiyoshi Egawa MD, PhD||Assistant Professor, 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)||Professor Emeritus||Hebrew University, Jerusalem, Israel|
|Arash Hadipour-Niktarash MD||Assistant Professor of Neurology||University of Colorado, Denver|
|Jennifer Hellier PhD||Teaching Assistant Professor of Anatomy and Neurobiology||University of Colorado, Denver|
|Theju Jacob PhD||Senior Research Scientist, Accuray Company||Raleigh-Durham, 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||Massachusetts General Hospital|
|Ji Lee MD, PhD||Assistant Professor in Child Neurology & Neuro-immunology||Columbia University, NY|
|Kyung-IL Park MD, PhD||Professor of Neurology||Seoul Paik Hospital, Inje University, South Korea|
|Jon Moussally MD||Instructor in Emergency Medicine||Salem Hospital, 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||Associate Medical Director, Takeda Pharmaceuticals||Cambridge, MA|
Albert Misko, MD PhD
|Research Scientist, Novartis||Cambridge, MA|
|Megan Audette||SUNY Upstate Medical University, Syracuse, NY||Resident Physician, Emergency Medicine, University of Wisconsin|
|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||Boston University||Physician, Internal Medicine, University of Chicago Hospital|
|Humzah Mahmood||Boston University, Boston, MA||BSc-2016, Biomedical Engineering|
|Camila Cabarello||MIT, Cambridge, MA||PhD Student-2023, CANDLab, Yale University|
|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||Resident Physician, Pediatrics, Vanderbilt University Medical Center, Nashville, TN|
|Britney Pitter||Morehouse School of Medicine, Atlanta GA||MD 2022|