DNA Microarrays and Epilepsy Research

DNA Microarrays and Epilepsy Research
October 4, 2002
Bethesda, Maryland

• Introduction
  
• Background
  
• Discussion
  
• Recommendations/Conclusions
  
• Participants
  
• NIH Staff

Introduction

The Curing Epilepsy: Focus on the Future conference held in March 2000 changed the course of epilepsy research from treating symptoms to curing epilepsy. The goals were to prevent epilepsy in those at risk and to provide treatment for individuals who develop the disorder with no seizures and no side effects. Benchmarks were established to judge progress in epilepsy research resulting from the conference. The benchmarks covered three areas: basic research on prevention of epilepsy, clinical research on prevention of epilepsy after identification of susceptible brain regions, and treatments for epilepsy. One of the benchmarks - Benchmark I.A.3: Establish a collaborative network that enables investigators to compare results of gene-chip analyses arising from different models of epileptogenesis and epilepsy - was created to encourage epilepsy researchers to use DNA microarrays and to be able to compare their results. The study of epilepsy could benefit from identification of genes whose expression levels are altered in the disease versus the normative state. This could provide epilepsy researchers with diagnostic markers of the epilepsies. To support research using DNA microarrays, the NINDS and NIMH have sponsored three centers, which came on line on June 1, 2002. The three centers are integrated into a consortium and RNA samples can be sent to any one of the centers for processing, labeling of arrays, and incorporation of the results into a center consortium-specific database.

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Background

The goal of the workshop was to 1) identify technical and experimental issues involved in using DNA microarrays for epilepsy research, 2) come up with recommendations for how to circumvent potential problems, and 3) involve each of the three microarray centers funded by NINDS and NIMH in the design, implementation and analysis of experiments. A major goal was to encourage gene expression profiling in epilepsy research. To do this NINDS brought together experts in Epilepsy, DNA microarrays, statistics and computer databases for microarrays to devise a strategy for implementing the use of microarrays in the study of epilepsy. The topics for discussion included sample preparation, tissue heterogeneity, statistical analysis, data sharing, and cross-platform data comparisons and selection of animal models.

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Discussion

The recently established DNA Microarray centers were able to address the discussion topics of sample handling, data storage, statistical analysis and experimental design. Dietrich Stephan's group at the Research Center for Genetic Medicine, which is part of the Children's Research Institute, will provide collaborative advice on experimental design. Thus, samples generated from the initial set of experiments by epilepsy researchers will be sent to the Microarray Consortium for processing. After much discussion on what initial experiments could be done by participants at the workshop and by epilepsy researchers worldwide, Dr. Ray Dingledine, who chaired the workshop, volunteered to write and distribute a detailed proposal of experiments designed to shed light on the genesis of epilepsy in mouse models of the disorder.

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Recommendations/Conclusions

Two recommendations were made: 1) establish the NINDS Task Force on Multi-Laboratory Consortium for Microarray Experiments in Epilepsy and 2) utilize the microarray centers because of their expertise, which would eliminate a significant source of experimental variability.

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Participants

Peter Crino, M.D., Ph.D.
Department of Neurology
3 West Gates Bldg.
University of Pennsylvania Medical Center
3400 Spruce St.
Philadelphia, PA 19104
Email: crinop@mail.med.upenn.edu

Raymond Dingledine, Ph.D.
Emory University School of Medicine
Department of Pharmacology
5001 Rollins Research Center
1510 Clifton Road
Atlanta, GA 30322-3090
Email: rdingledine@pharm.emory.edu

Robert Elliott, Ph.D.
Program in Brain Plasticity and Epilepsy
Department of Neurology
Beth Israel Deaconess Medical Center
Harvard Institutes of Medicine, Rm. 858
77 Avenue Louis Pasteur
Boston, MA 02115.
Email: relliott@caregroup.harvard.edu

Daniel H. Geschwind, M.D., Ph.D.
Assistant Professor
Department of Neurology
Director
Neurogenetics Program
UCLA School of Medicine
710 Westwood Plaza, RNRC 1-145
Los Angeles, CA 90095
Email: dhg@ucla.edu

Jessie Gu, Ph.D.
Principal Scientist
Bioinformatics and Target Discovery
UCB Research Inc.
840 Memorial Dr
Cambridge, MA 02139
Email: Jessie.Gu@ucb-group.com

David Henshall, Ph.D.
Assistant Scientist
Legacy Research
RS DOW Neurobiology Labs
1225 NE 2nd Avenue
Portland, OR 97232
Email: dhenshall@downeurobiology.org

Frances E. Jensen, M.D.
Harvard Medical School
Children's Hospital
Department of Neurology
300 Longwood Avenue, Enders 348
Boston, MA 02115
Email: frances.jensen@tch.harvard.edu

Fredrik Kamme, PhD.
Johnson & Johnson Pharamaceutical Research and Development, LLC
3210 Merryfield Row
San Diego CA 92121
Email: fkamme@prius.jnj.com

Katarzyna Lukasiuk, Ph.D.
Epilepsy Research Laboratory
A.I.Virtanen Institute for Molecular Sciences
University of Kuopio
P.O.Box 1627
Neulaniementie 1
FIN-70 211 Kuopio, FINLAND
Email: Katarzyna.Lukasiuk@uku.fi

Lisa McShane, Ph.D.
National Cancer Institute
Biometric Research Branch
Room 8126, Executive Plaza North
MSC, 7434
6130 Executive Boulevard
Bethesda, MD 20892
Email: McShaneL@CTEP.NCI.NIH.gov

Jeff Noebels, M.D.
Professor
Department of Neurology
Baylor College of Medicine
One Baylor Plaza
Houston, TX 77030
Email: jnoebels@bcm.tmc.edu

Asla Pitkanen, M.D., Ph.D.
Professor of Neurobiology
University of Kuopio
Epilepsy Research Laboratory
A.I. Virtanen Institute for Molecular Sciences
Neulaniementie 1
Kuopio, FIN-70 211, FINLAND
Email: asla.pitkanen@uku.fi

Dietrich Stephan, Ph.D.
Research Center for Genetic Medicine
Children's Research Institute
111 Michigan Avenue, N.W.
Washington, D.C. 20010
Email: dstephan@cnmcresearch.org

Miklos Toth, M.D., Ph.D.
Weill Medical College of Cornell
Dept of Pharmacology
1300 York Ave
New York, NY 10021
Email: mtoth@mail.med.cornell.edu

NIH Staff

Robert Baughman, Ph.D.
National Institute of Neurological Disorders and Stroke
National Institutes of Health
6001 Executive Boulevard
Room 2137
Bethesda, MD 20892-9527
Phone: 301-496-1779
Fax: 301-402-1501
Email: baughmar@ninds.nih.gov

Chen, Daofen, Ph.D.
National Institute of Neurological Disorders and Stroke
National Institutes of Health
6001 Executive Boulevard
Room 2131
Bethesda, MD 20892-9527
Phone: 301-451-6858
Fax: 301-402-1501
Email: daofen_chen@nih.gov

Meena Hiremath, Ph.D.
National Institute of Neurological Disorders and Stroke
National Institutes of Health
NSC 2141
6001 Executive Boulevard
Bethesda, Maryland 20892-9520
Phone: (301) 496-0656
Fax: (301) 402-1501
Email: hirematm@ninds.nih.gov

Margaret Jacobs
National Institute of Neurological Disorders and Stroke
National Institutes of Health
NSC 2138
6001 Executive Boulevard
Bethesda, Maryland 20892-9520
Phone: (301) 496-1917
Fax: (301) 402-1501
Email: jacobsm@ninds.nih.gov

Christina King
National Institute of Neurological Disorders and Stroke
National Institutes of Health
NSC 2121B
6001 Executive Boulevard
Bethesda, Maryland 20892-9520
Phone: (301) 451-9621
Fax: (301) 402-1501
Email: kingc@ninds.nih.gov

Yuan Liu, Ph.D.
National Institute of Neurological Disorders and Stroke
National Institutes of Health
NSC 2110
6001 Executive Boulevard
Bethesda, Maryland 20892-9520
Phone: (301) 496-3108
Fax: (301) 402-1501
Email: liuyuan2@ninds.nih.gov

Thomas Miller, Ph.D.
National Institute of Neurological Disorders and Stroke
National Institutes of Health
6001 Executive Boulevard
Room 2139
Bethesda, MD 20892-9527
Phone: 301-496-1779
Fax: 301-402-1501 Fax
Email: millert@ninds.nih.gov

Michael A. Rogawski, M.D., Ph.D.
Epilepsy Research Section
National Institute of Neurological Disorders and Stroke
49 Convent Drive Room 5A-75 MSC 4457
Bethesda, MD 20892-4457
Phone: 301-496-8013
Fax: 775-249-7715
Email: michael.rogawski@nih.gov

Paul Scott, Ph.D.
National Institute of Neurological Disorders and Stroke
National Institutes of Health
Science
Office of Science Policy and Planning
31 Center Drive, Room 8A03
Bethesda, Maryland 20892
Phone: (301) 496-4733
Fax: (301) 480-9172
Email: scottp@ninds.nih.gov

Randall R. Stewart, Ph.D.
National Institute of Neurological Disorders and Stroke
National Institutes of Health
NSC 2135
6001 Executive Boulevard
Bethesda, Maryland 20892-9520
Phone: (301) 496-6460
Fax: (301) 402-1501
Email: stewartr@ninds.nih.gov

Danilo Tagle, Ph.D.
National Institute of Neurological Disorders and Stroke
National Institutes of Health
NSC 2133
6001 Executive Boulevard
Bethesda, Maryland 20892-9520
Phone: (301) 451-8342
Fax: (301) 402-1501
Email: tagled@ninds.nih.gov

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