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
University of Pennsylvania Medical Center

Raymond Dingledine, Ph.D.
Emory University School of Medicine
Department of Pharmacology

Robert Elliott, Ph.D.
Program in Brain Plasticity and Epilepsy
Department of Neurology
Beth Israel Deaconess Medical Center

Daniel H. Geschwind, M.D., Ph.D.
Assistant Professor
Department of Neurology
Director
Neurogenetics Program
UCLA School of Medicine

Jessie Gu, Ph.D.
Principal Scientist
Bioinformatics and Target Discovery
UCB Research Inc.

David Henshall, Ph.D.
Assistant Scientist
Legacy Research
RS DOW Neurobiology Labs

Frances E. Jensen, M.D.
Harvard Medical School
Children's Hospital
Department of Neurology

Fredrik Kamme, PhD.
Johnson & Johnson Pharamaceutical Research and Development, LLC

Katarzyna Lukasiuk, Ph.D.
Epilepsy Research Laboratory
A.I.Virtanen Institute for Molecular Sciences
University of Kuopio

Lisa McShane, Ph.D.
National Cancer Institute
Biometric Research Branch

Jeff Noebels, M.D.
Professor
Department of Neurology
Baylor College of Medicine

Asla Pitkanen, M.D., Ph.D.
Professor of Neurobiology
University of Kuopio
Epilepsy Research Laboratory
A.I. Virtanen Institute for Molecular Sciences

Dietrich Stephan, Ph.D.
Research Center for Genetic Medicine
Children's Research Institute

Miklos Toth, M.D., Ph.D.
Weill Medical College of Cornell
Dept of Pharmacology

NIH Staff

Robert Baughman, Ph.D.
National Institute of Neurological Disorders and Stroke
National Institutes of Health

Chen, Daofen, Ph.D.
National Institute of Neurological Disorders and Stroke
National Institutes of Health

Meena Hiremath, Ph.D.
National Institute of Neurological Disorders and Stroke
National Institutes of Health

Margaret Jacobs
National Institute of Neurological Disorders and Stroke
National Institutes of Health

Christina King
National Institute of Neurological Disorders and Stroke
National Institutes of Health

Yuan Liu, Ph.D.
National Institute of Neurological Disorders and Stroke
National Institutes of Health

Thomas Miller, Ph.D.
National Institute of Neurological Disorders and Stroke
National Institutes of Health

Michael A. Rogawski, M.D., Ph.D.
Epilepsy Research Section
National Institute of Neurological Disorders and Stroke

Paul Scott, Ph.D.
National Institute of Neurological Disorders and Stroke
National Institutes of Health

Randall R. Stewart, Ph.D.
National Institute of Neurological Disorders and Stroke
National Institutes of Health

Danilo Tagle, Ph.D.
National Institute of Neurological Disorders and Stroke
National Institutes of Health

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