Andrew Escayg, Ph.D.
Additional Contact Information
Whitehead Biomedical Research Building
615 Michael St.
Atlanta, GA 30322
Our lab uses a combination of human and mouse genetics, mouse disease models and genome analysis/bioinformatics in order to determine the molecular basis of inherited neurological disorders. We have a broad interest in neurological/neuropsychiatric diseases and we are currently working on epilepsy, abnormalities in sleep architecture and the stress response, and movement disorders. The long-term goal of our research is to develop better diagnostic tools and more effective therapeutic agents.
Of particular interest to us is the role of voltage-gated ion channels in disease. Voltage-gated ion channels play a critical role in neuronal signaling and the maintenance of normal nervous system function. Diseases that result from mutations in ion channel genes are called channelopathies. Channelopathies underlie a wide range of disorders that include cardiac and skeletal muscle defects and neurological disorders such as epilepsy.
Our research can be divided into a number of different components.
Human disease gene identification and analysis.One component of our research is the identification of genes responsible for inherited human neurological disorders such as epilepsy. If we suspect that a known gene is mutated in the family then the candidate gene is directly screened for novel mutations. If we suspect that a novel gene may be responsible, then we use a variety of genetic techniques in order to identify the novel disease gene. Using these approaches we have identified several new mutations in the voltage-gated sodium channel gene, SCN1A, that is responsible for two forms of dominant epilepsy; Genetic Epilepsy with Febrile Seizures Plus (GEFS+) and Dravet Syndrome. GEFS+ is characterized by febrile (fever induced) seizures that persist beyond the age of six and the development of adult epilepsy. Dravet syndrome is a severe, debilitating childhood epilepsy characterized by febrile and afebrile seizures, mental retardation and ataxia.
Mouse genetics. Understanding the mechanisms that lead to disease is an important step towards the development of improved therapies. In order to understand how specific mutations cause disease, mice carrying specific human mutations can be generated. We have used this approach to generate transgenic, knock-in and knock-out mice that carry human epilepsy mutations. These mice reproduce many features of the human disease and are currently under investigation for seizure phenotypes and behavioral abnormalities.
Development of novel treatments for epilepsy. Approximately 35% of patients with epilepsy do not achieve effective seizure control with available anti-epilepsy medications. We are actively involved in evaluating the efficacy of alternative treatment such as the ketogenic diet. We are also developing novel treatments including AAV-mediated shRNA therapies.
The completion of the human genome project and the availability of genomic sequences from an increasing number of species provide a unique opportunity to understand the organization of the human genome. We are particularly interested in understanding the genetic elements that regulate the expression levels of identified disease genes. This component of our research requires the use of bioinformatics and sequence analysis techniques.
Areas of Specialization
- The genetics of neurological disorders (Neurogenetics)
- Human and mouse genetics
- Disease gene identification
- The generation of mouse models of human disease
- The role of ion channel genes in disease
- Genome analysis/bioinformatics
- Postdoctoral Training, Department of Human Genetics, University of Michigan, 1997-2002
- PhD, Molecular Genetics, Lincoln University, New Zealand,1995
- MS, Analytical Chemistry, The University of the West Indies, Trinidad,1990
- BS, Chemistry, The University of the West Indies, Trinidad,1987
- The Society for Neuroscience
- The American Epilepsy Society
- View publications on PudMed