Despite decades of research that have led to an understanding of many causes of epilepsy and yielded over fifteen new antiseizure drugs and novel non-drug therapies, there remain no treatments that prevent epilepsy, nor are there ways to identify and prove such treatments. A major obstacle to research in this area is the fact that studies from single institutions are inadequate to answer the most important questions. The Epilepsy Bioinformatics Study for Antiepileptogenic Therapy (EpiBioS4Rx) is a large, international, multicenter Center without Walls (CWOW) to address this pressing need by using studies of animals and patients with traumatic brain injury (TBI) leading to post-traumatic epilepsy (PTE) to develop the techniques and patient populations necessary to carry out future cost effective full-scale clinical trials of epilepsy prevention therapies.

This is a project designed to facilitate the development of antiepileptogenic therapies by removing barriers and promoting large-scale collaborative research efforts by multidisciplinary teams of basic and clinical neuroscientists with access to extensive patient populations, well-defined and rigidly standardized animal models, and cutting-edge analytic methodology. We focus on antiepileptogenesis in PTE following TBI as this condition offers the best opportunity to determine the time of onset of the epileptogenic process in patients.

The EpiBioS4Rx Scientific Premise is: Epileptogenesis after TBI can be prevented with specific treatments; the identification of relevant biomarkers and performance of rigorous preclinical trials will permit the future design and performance of economically feasible full-scale clinical trials of antiepileptogenic therapies. Based on the work from a P20 planning grant, our program will consist of the following: (1) identify biomarkers of epileptogenesis in our animal model and in patients, (2) Develop and utilize a standardized platform for preclinical trials of potential antiepileptogenic (AEG) drugs, (3) Identify 1 or more lead antiepileptogenic drugs for a future interventional clinical trial, (4) Establish a network of advanced TBI centers capable of carrying out future clinical trials featuring our lead antiepileptogenic drugs used in the context of a personalized, medicine-based approach utilizing our panel of biomarkers, and (5) Develop and incorporate a public engagement program involving the mutual education and collaboration of consumers, consumer organizations and professionals to design and execute future large-scale interventional clinical trials of antiepileptogenic therapies.

DATA COLLECTION, ANALYSIS AND TRIAL DESIGN

Study Design

We have chosen to focus on disease prevention, but results of our efforts could also inform approaches to disease modification. We plan a translational, international, multiple project, multicenter, multidisciplinary approach to: 1) identify biomarkers of epileptogenesis in our animal model and in patients, 2) develop a standardized protocol for preclinical trials of potential antiepileptogenic therapies and identify one or more potential antiepileptogenic agent, and 3) create open shared resources for the entire epilepsy research community, including an epilepsy specific bioinformatics platform and database, a robust animal model of TBI leading to PTE, a standardized preclinical protocol for the evaluation of novel antiepileptogenic therapies, a network of TBI centers capable of carrying out future clinical trials of potential antiepileptogenic interventions, and a public engagement program committed to recruitment and retention. We anticipate this work will result in one or more candidate antiepileptogenic treatments at the end of the 5-year funding period, as well as the biomarker information, resources, expertise, and patient population to carry out an economically feasible, full-scale clinical trial.

1) Identification of biomarkers and epileptogenesis in animals and patients: Even if a potential antiepileptogenic agent existed, there is no at-risk patient population in which to test its success cost effectively. We have created a collaborative multicenter, international research effort composed of multidisciplinary teams of basic and clinical neuroscientists with access to robust, well-defined animal models, extensive patient populations, standardized protocols, and cutting-edge analytic methodology. We expect that the predictive power will likely require a combination of electrophysiological, neuroimaging, and biochemical biomarkers measured at different post-injury time points, to diagnose with high sensitivity and specificity ongoing epileptogenesis independent of the severity of brain damage. We anticipate these studies will also provide insights into the fundamental neuronal mechanisms of these processes and inform basic research into novel targets for antiepileptogenic interventions.

2) Standardized preclinical trials of potential antiepileptogenic therapies and identification of one or more potential antiepileptogenic agents: Scientific evidence suggests that many compounds could have antiepileptogenic potential, but adequate evidence to justify a clinical trial is lacking, in large part due to failure to reproduce promising results in more than one laboratory and difficulty translating the preclinical to the clinical condition. This failure reflects the absence of a valid animal model of human epileptogenesis and a standardized preclinical trial protocol, which adheres to the same rigid criteria used for clinical trials. We have developed a robust standardized fluid percussion injury (FPI) rat model of TBI leading to PTE in our laboratories that replicates epileptogenesis following TBI in patients with moderate to severe TBI and have been carrying out parallel reiterative animal/human studies. We will use this model also to create a rigorous standardized protocol for testing potential antiepileptogenic therapies utilizing a double-blind randomized approach and the therapy-specific biomarkers as they become available in a manner that is reproducible in any laboratory that follows the standardized protocol. We anticipate that the identification and validation of antiepileptogenic treatments in the preclinical trials using the profile of identified biomarkers from the parallel animal/human research paradigms, together with the establishment of a network of TBI centers with appropriate facilities and expertise will enable preparation for a future, economically feasible, cost-effective, full-scale, clinical trial of safety and efficacy of antiepileptogenic therapies to prevent PTE.

3) Creation of open and shared resources for the entire epilepsy community: A key to the success of large multidisciplinary research efforts that generate “big data” is an effective shared bioinformatics approach to data storage and analysis. With the EpiBioS4Rx P20 planning grant, we have succeeded in developing a multimodality, interactive, open access bioinformatics platform specific for epilepsy and are using this resource to carry out our studies. We have achieved this short-term goal in part by leveraging programs already supported by NIH and other funding sources. We have unified the functionality between the International Electrophysiology Web Portal (iEEG.org) platform of Dr. Brian Litt, who will be providing his expertise as a consultant, and the Laboratory of Neuroimaging (LONI) platform of Dr. Arthur Toga. The latter has supported extensive studies of biomarkers and treatments for Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, the genetic basis of aspects of hippocampal structure, and the exploration of computational genomics challenges. We are currently applying our bioinformatics algorithms to available animal and human electrophysiological and imaging data, and are collecting molecular, cellular, and other data to be integrated into this analytic process. Dr. Vespa from UCLA has recruited 13 TBI centers that will follow patients for two years to participate in our proposed clinical biomarker project. They will constitute a network with the facilities and expertise to perform the subsequent clinical trials once they are justified by preclinical studies and made feasible by biomarker identification. For the design of the future clinical trials, we developed an extensive public outreach program of epilepsy and TBI consumer groups committed to recruitment and retention of subjects and consumer satisfaction. We plan to make available to the greater epilepsy community all of our bioinformatics tools and resources, databank, biobank, experimental protocols for a standardized TBI/PTE animal model and preclinical evaluation of antiepileptogenic therapies, a network of TBI centers with facilities and expertise to carry out future clinical trials of antiepileptogenic interventions. To this end, collaborations have been established with a number of related programs, including Epi4K, EpGP, EPITARGET, FEBSTAT, TRACK-TBI, CENTER-TBI, ADAPT, CSR, and the VA Epilepsy Centers of Excellence to expand the patient population available for future clinical trials.

Core Interactions

Specific Aims

Specific Aim 1: Carry out focused multicenter, collaborative, preclinical and clinical investigations to identify and validate biomarkers of Epileptogenesis following TBI and preclinical investigations to evaluate potential interventions that prevent the development of PTE as well as their effects on the identified biomarkers of epileptogenesis in a standardized animal model of TBI/PTE.

Research Project 1: Animal studies at 3 centers using a standardized lateral fluid percussion injury rat model of PTE to identify plasma, imaging, and electrophysiological biomarkers measured at different post-injury time points, alone or in combination, to diagnose with high sensitivity and specificity ongoing epileptogenesis independent of the severity of brain damage.

Research Project 2: Animal studies at 4 centers to identify targets and biomarkers for treatment implementation, which in combination with the biomarkers of epileptogenesis from Project 1, will guide rigorous randomized preclinical trials of potential AEG interventions to prevent PTE in the standardized animal model of TBI/PTE.

Research Project 3: Clinical/translational studies at 13 experienced TBI centers will identify biomarkers and validate in humans the biomarkers identified in Projects 1 and 2.

Specific Aim 2: Our multi-modal epilepsy-specific bioinformatics approaches will be applied to the results obtained in Projects 1, 2, and 3 to derive a combination of biomarkers that will reliably predict epileptogenesis following TBI in both animals and humans and identify specific AEG treatments to be used in future clinical trials. Following the completion of the aims, and in partnership with the consumer and scientific groups in the Public Engagement Core, our approach will permit the design and execution of a feasible, cost-effective, personalized medicine-focused, interventional, randomized, international clinical trial for AEG therapies in TBI.

Innovation

EpiBioS4Rx is a unique translational project. It brings together human and animal epileptogenesis research on TBI with active participation of consumer advocates to provide all the necessary information, resources, expertise, and patient population to carry out an economically feasible, full-scale clinical trial of one or more antiepileptogenic therapies at the end of the 5 year funding period.

EpiBioS4Rx has integrated existing interactive multimodality bioinformatics platforms. The unique combined platform is capable of acquiring, storing, and analyzing electrophysiological, imaging, molecular, and cellular data from animal and clinical studies that have not been used to study epileptogenesis previously, and that will constitute an open-access, epilepsy-specific database and analytics resource.

EpiBioS4Rx will develop the first validated multimodal biomarker panel for preclinical and clinical antiepileptogenesis trials.

EpiBioS4Rx will develop the first rigorous preclinical multicenter therapy-development pipeline for promising antiepileptogenic treatments to facilitate their testing in a future antiepileptogenesis clinical trial in patients with TBI. We propose to screen 5 treatment protocols for their effect on modifying PTE biomarkers in our animal model of TBI, test the leading compound for its efficacy in preventing PTE and thus prepare for a future clinical trial of the leading compound.

EpiBioS4Rx will identify at least one compound that shows an anti-epileptogenic effect in a rigorous, long-term, multicenter pre-clinical trial that is ready to proceed to be tested in a clinical trial utilizing the EpiBioS4Rx clinical TBI centers and biomarkers.

EpiBioS4Rx has enlisted the enthusiastic participation of 13 advanced clinical TBI programs. These programs have not studied epilepsy as part of their research in the past, will use the data from their extensive subject populations to identify likely biomarkers of epileptogenesis, will validate biomarkers identified in animal TBI studies, and will establish a network of advanced TBI centers with continuous EEG monitoring and other resources, expertise, and patient populations to carry out future full-scale clinical trials of antiepileptogenic agents identified in this study or others.

EpiBioS4Rx will utilize common data elements, and a rigorously designed, standardized protocol for preclinical trials of potential antiepileptogenic agents. This unique paradigm will employ therapy specific biomarkers identified in animal and human studies to identify one or more antiepileptogenic agents for full-scale clinical trials.

Our Public Engagement Core will, for the first time, bring together epilepsy and TBI advocacy and consumer groups to address common interests and concerns. This effort will not only involve patients with PTE but also patients at risk for developing PTE and will facilitate recruitment and retention of subjects for future clinical trials.

EpiBioS4Rx has developed a Charter and Publication Policy that not only establishes a code of equity among investigators but also outlines how our data, tools, and resources will be made available to the entire epilepsy community.

Infrastructure

EpiBioS4Rx has developed an extensible, portable and robust infrastructure which includes a database portal to a distributed federated architecture, a graphical framework for computational data processing via web-application clients and back-end Grid servers, and secure access control to data and services, utilizing reliable hardware resources (storage, processing and networking).

The informatics approach of this antiepileptogenetic study will involve management of heterogeneous data, data mining, exploratory data analysis, modeling, and interrogation of multimodal and multiform datasets. Specifically, the data that we will manage, process and disseminate includes proteomics data, genomics data, EEG, multichannel volumetric neuroimaging data, neurocognitive and behavioral data for patients as well as data from a diverse array of epileptogenetic animal models.

Data Federation

To enable rapid development and utilize all existing infrastructure we intend to design an efficient data federation architecture that facilitates the traversal, discovery, upload and retrieval of the imaging, genetics, clinical, demographic and behavioral data to/from all distributed and heterogeneous data sources provide by the participating institutions. This approach will utilize the available database services and leave current dataset in place avoiding data redundancy. This data federation approach will support standard data operations using an integrated virtual portal view where the real data is stored in multiple diverse sources; however it will be accessible via one centralized location. The original data sources will remain under the control of each hosting institution and data will be pulled, queried and retrieved on demand via the federated portal access.

Hardware Infrastructure

We have a significant hardware infrastructure that provides high performance, security and reliability. The fault-tolerant network infrastructure has no single points of failure having multiple switches, routers and Internet connections. A firewall appliance protects and segments the network traffic, permitting only authorized ingress and egress through. Multiple redundant database, application and web servers ensure service continuity in the event of a single system failure and also provide improved performance through load balancing of requests across the multiple machines. To augment the network-based security practices and to ensure compliance with privacy requirements, the servers utilize SSL encryption for all data transfers. Client-side de-identification of files using a signed applet integrated into the software ensures that only de-identified data is transmitted to the servers. Post-transfer redundancy checking on the files is performed to guarantee the integrity of the data. To date, we have neither suffered a system disaster, nor lost data; however as an added layer of security, sophisticated backup mechanisms are in place to protect the integrity of data.

Research & Data Analysis

Streamlined Data Consolidation: Users will be able to upload their raw data files directly to an extended version of the LONI infrastructure where they will automatically be classified, converted, and annotated. By automating much of this process, researchers both uploading and downloading data will be spared the time and effort currently involved in accessing and sharing epilepsy data. This streamlined data consolidation will increase the financial efficiency and scientific productivity of the CWOW and the broader epilepsy research community. In addition, physical samples will be brought together in a single biobank, further reducing coordination challenges. Much of these data have already been collected by the PIs presenting this proposal; however, the huge size of these data combined with the many different file formats makes effective navigation currently frustratingly labor-intensive and error-prone.

User-friendly data search and navigation: By converting data to consistent file formats and tagging that data with metadata, the CWOW will enable Google-style search of all available epilepsy data. However, because data will be interlinked and co-registered across data sets and modalities, the search functionality will not simply match data against individual items like Google—rather, it will find interlinked combinations of data (even across modalities and data sources) that match the desired criteria. This enables sophisticated custom searches that match the functionality of predefined query forms. Users will be able to browse data in its most appropriate visual representation and pivot from one data view or modality to another. Through our experiences with LONI, we have learned the access control and sharing mechanisms required by the community and how effectively to enable inter-project as well as community-scale data sharing. Key components include giving users explicit access control for their data and results as well as providing project groups for larger-scale permissions management. Furthermore, comparable tools that can be repurposed were developed for LONI as part of our planning grant and projects like ADNI.

Automated analysis: The LONI Pipeline contains a common framework for visual and programmatic construction of data-driven workflows for electrophysiology, imaging, and biosample data. We will customize these tools to the study of epilepsy data. With the aid of LONI’s workflow builder, complex analyses are represented visually, further supporting researchers’ investigations. Examples of Pipeline applications include developing a unified coordinate space for seizure locations across organisms, using string similarity and value overlap to predict that different contributor metadata fields are the same, and providing graphical interfaces for linking data. Co-registration algorithms will typically be invoked at upload-time but may be triggered later manually for further refinement. The IAC will provide MRI supervision and integration from different scanners and centers by supervising phantom studies, assessing quality, and fixing problems with heterogeneity. While LONI has primarily used Pipeline for human data, it has also been used to study neural networks of the mouse neocortex. The CWOW would further expand these capabilities, providing robust workflow pipelines for both humans and animal models.

Iterative improvement using novel analytical tools: The sheer quantity of data and the noise inherent in the data necessitates the development of novel analytical tools, incorporating the most recently developed mathematical and statistical tools to discover previously undetected biomarkers. Dr. Bragin et al. recently discovered a novel biomarker, repetitive high frequency oscillations and spikes (rHFOSs). Dr. Gotman, a consultant on this project, has established tools to study the relationship between spikes and HFOs and showed their links to epileptogenesis. Dr. Duncan has developed sophisticated mathematical methods to analyze both animal and human data separately and for trans-species comparisons.

We are keenly aware of multiple conceptual and technical issues regarding data analyses with biomarkers, including within subject correlation, multiplicity, multiple clinical endpoints, and selection bias. Utilization of multiple statistical approaches will allow us to address these concerns in full.

Standardized sample collection, shipping, and biobank storage protocols: The project will define methods for harvesting, freezing, and storing tissue and other biosamples (i.e. serum). Data and tissue stored for collaborating preclinical trials, such as TRACK TBI, ALLO, PPMI, TRACKHD, ICBM, AIBL, ACE, ABIDE, 4RTNI, Mapp, and the Human Connectome Project already have these protocols in place with informatics provided by LONI. Animal protocols for storing parallel samples to humans will be stored and treated in a similar fashion to compare findings from parallel human and animal studies.

A data safety monitoring board (DSMB) will advise us as we perform a rigorous multicenter preclinical antiepileptogenesis trial using a blinded, vehicle-controlled randomized study design to determine the antiepileptogenic effect of the lead compound. The results of the three projects integrated with the IAC, following the close guidance of the DSMB, will assist in planning the optimal design of a future clinical antiepileptogenesis trial for successful drugs.

People

Who's who?

EpiBioS4Rx is a federated consortium of international research centers. Each component of EpiBioS4Rx is multicenter with multiple autonomous investigators.

Program Director

Co-Project 3 Lead

Jerome (Pete) Engel Jr., MD, PhD

Principal Investigator

Administrative Core, Management Comittee, Executive Committee, Steering Committee
Projects 1, 2, 3 (Co-Project Lead)

Department of Neurology
Ronald Reagan UCLA Medical Center
300 UCLA Medical Plaza, Suite B200
Los Angeles, CA 90095
UNITED STATES
Tel: (310) 825-5745
engel@ucla.edu

Project 2 Lead

Aristea Galanopoulou, MD, Ph.D

Principal Investigator

Executive Committee, Steering Committee,
Project 2 (Project Lead)

Albert Einstein College of Medicine
1410 Pelham Parkway South Kennedy Center Rm 306
Bronx NY 10461
UNITED STATES
Tel: (718) 430-3791 aristea.galanopoulou@einstein.yu.edu

PEC Project Lead

Solomon (Nico) L Moshé, MD

Principal Investigator

PEC, Management Comittee, Executive Committee, Steering Committee
Project 2

Albert Einstein College of Medicine
Department of Neurology
1410 Pelham Parkway South Kennedy Center Rm 316
Bronx NY 10461
Tel: 718-430-2447
solomon.moshe@einstein.yu.edu

Co-Project 1 Lead

Co-Project 2 Lead

Terence O'Brien, MD

Principal Investigator

Executive Committee, Steering Committee, Project 1(Co-Project Lead), 2 (Co-Project Lead), 3

The University of Melbourne
obrientj@unimelb.edu.au

Project 1 Lead

Co-Project 2 Lead

Asla Pitkänen, MD, PhD

Principal Investigator

Executive Committee, Steering Committee, Project 1 (Project Lead), 2

University of Eastern Finland
A.I. Virtanen Institute for Molecular Sciences
Department of Neurobiology
P.O.B. 1627 (Neulaniementie 2)
FI-70211 Kuopio
FINLAND
Telephone: +358 50 517 2091
Fax: +358 17 163 025
asla.pitkanen@uef.fi

Contact Principal Investigator

Arthur Toga, PhD

Principal Investigator

Administrative Core, Management Comittee, Executive Committee, Steering Committee
Projects 1, 2, 3

Laboratory of Neuro Imaging
Stevens Institute for Neuroimaging and Informatics
Keck School of Medicine of USC
University of Southern California
2025 Zonal Avenue
Los Angeles, CA 90033
UNITED STATES
Telephone: (323) 44-BRAIN (442-7246)
toga@loni.usc.edu

Project 3 Lead

Paul M. Vespa, FCCM, FAAN, MD

Principal Investigator

Executive Committee, Steering Committee
Project 3 (Project Lead)

UCLA Department of Neurosurgery
Ronald Regan UCLA Medical Center
757 Westwood Plaza, Suite 6236A
Los Angeles, CA 90095-7436 UNITED STATES
Telephone: (310) 206-4100
pvespa@mednet.ucla.edu

Co-Project 1 Lead

Richard Staba, PhD

Investigator

Department of Neurology
Ronald Reagan UCLA Medical Center
300 UCLA Medical Plaza, Suite B200
Los Angeles, CA 90095
UNITED STATES
Telephone: (310) 825-5745
rstaba@mednet.ucla.edu

PEC Co-Project Lead, Co-investigator

Nathalie Jette, MD, MSc, FRCPC

Investigator

PEC, Steering Committee

Professor Neurology and Community Health Sciences
Director Epilepsy Clinic and Seizure Monitoring Unit, Calgary Epilepsy Program
Hotchkiss Brain Institute & O'Brien Institute for Public Health
University of Calgary Cumming School of Medicine
1403 29 Street NW
Calgary, Alberta T2N 2T9
Tel: 403-944-2760
Fax: 403-944-0988
nathalie.jette@albertahealthservices.ca
Denes Agoston

Investigator

Project 2

Uniformed Services University of the Health Sciences Division
vagoston@usuhs.mil
Maranatha Ayodele

Investigator

Project 3

University of Miami Miller School of Medicine
mayodele@med.miami.edu
Neeraj Badjatia

Investigator

Project 3

University of Maryland, Baltimore
nbadjatia@som.umaryland.edu
Michael Bell

Investigator

Project 3

University of Pittsburgh
bellmj4@upmc.edu
Craig Branch

Investigator

Project 2

Albert Einstein College of Medicine
1300 Morris Park Avenue
Bronx, NY 10461
craig.branch@einstein.yu.edu
Manuel Buitrago Blanco

Investigator

UCLA
mblanco@mednet.ucla.edu
Ross Bullock

Investigator

Project 3

University of Miami Miller School of Medicine
rbullock@miami.edu
Jan Claassen

Investigator

Project 3

Columbia University
jc1439@cumc.columbia.edu
Robert Clarke

Investigator

Project 3

University of Pittsburgh
clarkrs@ccm.upmc.edu
James Cloyd

Investigator

Project 1, 2

Regents of the University of Minnesota
Cloyd001@umn.edu
Jonathan Coles

Investigator

Project 3

University of Cambridge
jpc44@wbic.cam.ac.uk
Lisa Coles

Investigator

Project 2

Regents of the University of Minnesota
durh0016@umn.edu
Karen Crawford

Investigator

Project 3

Laboratory of Neuro Imaging
Stevens Institute for Neuroimaging and Informatics
Keck School of Medicine of USC
University of Southern California
2025 Zonal Avenue
Los Angeles, CA 90033
UNITED STATES
Telephone: (323) 44-BRAIN (442-7246)
Karen.Crawford@loni.usc.edu
Dominique Duncan, Ph.D

Investigator

IAC, Steering Committee

Laboratory of Neuro Imaging
Stevens Institute for Neuroimaging and Informatics
Keck School of Medicine of USC
University of Southern California
2025 Zonal Avenue
Los Angeles, CA 90033
UNITED STATES
Telephone: (323) 44-BRAIN (442-7246)
dominique.duncan@loni.usc.edu
Benjamin Ellingson

Investigator

Project 3

UCLA
bellingson@mednet.ucla.edu
Brandon Foreman

Investigator

Project 3

University of Cincinnati
brandon.foreman@uc.edu
Emily Gilmore

Investigator

Project 3

Yale University
emily.gilmore@yale.edu
Olli Grohn

Investigator

Project 1, 2

University of Eastern Finland
olli.grohn@uef.fi
Neil Harris

Project 3

Investigator

UCLA
ngharris@mednet.ucla.edu
Jed Hartings

Investigator

Project 3

University of Cincinnati
hartingja@ucmail.uc.edu
Lawrence Hirsch

Investigator

Project 3

Yale University
lawrence.hirsch@yale.edu
Leigh Johnston

Investigator

Project 1, 2

The University of Melbourne
l.johnston@unimelb.edu.au
Nigel Jones

Investigator

Project 1, 2

The University of Melbourne
ncjones@unimelb.edu.au
Andres Kanner

Investigator

Project 3

University of Miami Miller School of Medicine
a.kanner@miami.edu
David McArthur

Investigator

Project 3

UCLA
dmcarthur@mednet.ucla.edu
David Menon

Investigator

Project 3

University of Cambridge
dkm13@cam.ac.uk
Andrew Morokoff

Investigator

Project 1, 2

The University of Melbourne
morokoff@unimelb.edu.au
Martin Monti

Investigator

Project 3

UCLA
monti@psych.ucla.edu
Wenzhu Mowrey

Investigator

Project 2

Albert Einstein College of Medicine
1300 Morris Park Avenue
Bronx, NY 10461
wenzhu.mowrey@einstein.yu.edu
Thomas Naughton

Investigator

Project 2

Phoenix Children's Hosptial
tnaughton@phoenixchildrens.com
Kristine O'Phelan, MD

Investigator

Project 3

University of Miami Miller School of Medicine
kophelan@miami.edu
Rema Raman

Investigator

Project 3

Keck School of Medicine of USC
University of Southern California
remar@usc.edu
Courtney Robertson

Investigator

Project 3

Johns Hopkins University SOM
crober48@jhmi.edu
Eric Rosenthal

Investigator

Project 3

Massachusetts General Hospital
erosenthal@mgh.harvard.edu
Kevin Sheth

Investigator

Project 3

Yale University
kshethmd@gmail.com
Sandy Shultz

Investigator

Project 1, 2

The University of Melbourne
sandy.shultz@unimelb.edu.au
Terrance Snutch

Investigator

Project 2

University of British Columbia
snutch@msl.ubc.ca
Mark Wainwright

Investigator

Project 3

Northwestern
mwainwright@luriechildrens.org
Frederick Willyerd

Investigator

Project 3

Phoenix Children's Hosptial
fwillyerd@phoenixchildrens.com
Susan H. Connors

PEC Collaborator

President/CEO, Brain Injury Association of America
1608 Spring Hill Road, Suite 110, Vienna, VA 22182
Tel: 1-703-761-0750
Fax: 1-703-761-0755
shconnors@biausa.org
Daniel Correa, MD

PEC Collaborator

Instructor
Montefiore Medical Center / Albert Einstein College of Medicine
111 East 210th Street
Bronx, New York 10467
Tel: 1-718-920-2693
dcorrea@montefiore.org
Vicky Holets Whittemore, PhD

PEC Collaborator

NINDS/NIH Program Director
Channels, Synapses and Circuits
6001 Executive Blvd, Room 2133
Rockville, MD 20852
Tel: 1-301-496-1917
Vicky.whittemore@nih.gov
David J. Thurman, MD, MPH

PEC Collaborator

Adjunct Professor of Neurology
Emory University School of Medicine
Atlanta, GA, U.S.A.
Tel: 1-403-378-4565
djthurman1@gmail.co
Philip M. Gattone, M.Ed.

PEC Collaborator

President & CEO
Epilepsy Foundation
8301 Professional Place East, Suite 200
Landover, MD 20785-2353
Tel: 1-301-918-3700
pgattone@efa.org
Joyce A. Cramer

PEC Collaborator

Yale University School of Medicine (ret)
2207 Bancroft St., Unit 1501
Houston, TX 77027-3731
Tel: 713-552-0289
Fax: 203-500-9091
joyce.cramer@gmail.com
R. Andrew David

PEC Collaborator

Epilepsy Center of Excellence (127E)
VA Maryland Health Care System
10 N Greene St
Baltimore, MD 21201
Tel: 1-410-605-7000 x6578
Robert.David@va.gov
Dennis Dlugos, MD

PEC Collaborator

Children's Hospital of Philadelphia Care Network
3401 Civic Center Blvd
Philadelphia, PA 19104
Tel: 1-215-590-1719
dlugos@email.chop.edu
Gary Mathern, MD

PEC Collaborator

Brain Research Institute
University of California, Los Angeles
710 Westwood Plaza
Los Angeles, CA 90095
United States
Tel: 1-310-825-7961
gmathern@ucla.edu
Laura Lubbers Ph.D.

PEC Collaborator

Chief Scientific Officer
CURE | Citizens United for Research in Epilepsy
430 West Erie Street, Suite 210 | Chicago, Illinois 60654
Tel: 1-312-255-1801
laura.lubbers@cureepilepsy.org
Allison Heffer

PEC Collaborator

Patient Representative

Child Life Center
6 Tower Room 59C
Morgan Stanley Children's hospital of NY-Presbyterian
New York, New York 10032
Tel: 1-212-342-8577
aheffer160@aol.com
Robert Kotloski, MD

PEC Collaborator

Department of Neurology
1685 Highland Ave.
7th floor, MFCB
Madison, WI 53705-2281
Tel: 1-608-263-5448
kotloski@neurology.wisc.edu
Sunita Dergalust

PEC Collaborator

Clinical Pharmacist in Neurology and Neurosurgery, Residency Program Director for the PGY2 Neurology Speciality Pharmacy Residency Program
VA Greater Los Angeles Healthcare System
11301 Wilshire Blvd
Los Angeles, CA 90073
Tel: 1-310-268-3408
sunita.dergalust@va.gov
Margaret Jacobs

PEC Collaborator

Science Community Liaison
American Epilepsy Society
342 North Main Street
West Hartford, CT 06117
Tel: 1-312-255-1801
margaretpj704@gmail.com
Mr. & Mrs. Segal

PEC Collaborator

Caregivers
78 Carolyn Place
Chappaqua, NY 10514
Tel: 1-914-238-3157
labendz@aol.com rsegal@us.ibm.com
Denise Bartley, CNP

PEC Collaborator

PO Box 160
Northern Navajo Medical Center
Internal Medicine
Shiprock, NM 87420-0160
Tel: 1-505-368-7022
denise.bartley@ihs.gov
Karen Parko, MD

PEC Collaborator

San Francisco VA Medical Center Epilepsy Clinic of Excellence
4150 Clement Street
San Francisco, CA 94121
Tel: 1-415-221-4810
karen.parko@va.gov
Jessica Keenan Smith

PEC Collaborator

Founder and Managing Editor
Living Well With Epilepsy
Haddonfield, NJ 08033
http://livingwellwithepilepsy.com
Tel: 1-856-308-5377
jessica@livingwellwithepilepsy.com
Thomas Bleck, MD

Consultant

Rush University
tbleck@rush.edu
Ashley Bush
The University of Melbourne
bush@helix.mgh.harvard.edu
Dennis Dlugos
CHILDREN'S HOSPITAL OF PHILADELPHIA
DLUGOS@email.CHOP.edu
Robert Kowalski, MD

PEC Collaborator

Craig Hospital
3425 S. Clarkson St.
Englewood, CO 80113
Tel: 1-303-789-8028
rkowalski@craighospital.org
Jacqueline French

Consultant

NYU Langone Medical Center
Jacqueline.French@nyumc.org
Jean Gotman
McGill University
jean.gotman@mcgill.ca
Chris Hovens
The University of Melbourne
cbhovens@gmail.com
Angela Ostrom, Esq.

PEC Collaborator

Chief Legal Officer & Vice President Public Policy
Epilepsy Foundation
8301 Professional Place East
Landover, MD 20785
Tel: 1-301-918-3766
aostrom@efa.org
Mary Jo Pugh

PEC Collaborator

Co-Director: Research to Advance Community Health (ReACH)
Professor:
Department of Epidemiology and Biostatistics
Department of Medicine: General/Hospital Medicine
University of TX Health Science Center San Antonio
Research Scientist: South Texas Veterans Health Care System
7400 Merton Minter Street
San Antonio, TX 78229
Tel: (210) 842-3807
Fax: (210) 567-4423
pughm@uthscsa.edu VA email: maryjo.pugh2@va.gov
Emilio Perucca
International League Against Epilepsy
perucca@unipv.it
David Thurman
Emory University School of Medicine
david.j.thurman@emory.edu
Anatol Bragin
UCLA
abragin@mednet.ucla.edu
Karen Parko
UCSF
karen.parko@ucsf.edu
Brandy Fureman

SAB, PEC

Epilepsy Foundation
8301 Professional Place East, Suite 200
Landover MD 20785
Tel: 1-301-918-3742
bfureman@efa.org
Merab Kokaia

SAB

University of Lund
merab.kokaia@med.lu.se
Patrick Kwan

SAB

The Royal Melbourne Hospital
patrickkwan@cuhk.edu.hk
Samden Lhatoo, MD

SAB

Case Western Reserve University
Epilepsy Center - Lakeside 3222A
11100 Euclid Avenue
Cleveland, OH 44106-5040
Istvan Mody

SAB

UCLA
imody@mednet.ucla.edu
Roy Twyman

SAB

Janssen Research & Development, LLC
RTwyman@its.jnj.com

Program directed by the National Institute of Neurological Disorders and Stroke (NINDS) at NIH

Publications


Publications coming soon!

Each publication, press release, or other document about research supported by an NIH award must include an acknowledgment of NIH award support and a disclaimer such as “Research reported in this publication was supported by the National Institute Of Neurological Disorders And Stroke of the National Institutes of Health under Award Number U54NS100064. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health."

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