Department of Comparative Biosciences
- B.A. in Biology, Augustana College, 1985
- Ph.D. in Molecular Physiology and Biophysics, Vanderbilt University, 1992
- Transcriptional and epigenomic regulation of myelination.
- Role of Chromatin Structure in Gene Regulation.
I have a long standing interest in the interplay of chromatin structure and gene regulation, and I have focused this interest in the study of genomic and epigenetic determinants of the myelination process. These studies have encompassed analysis of miRNA pathways as well as the functions of the NuRD chromatin remodeling complex in peripheral nerve development. We were the first to develop in vivo chromatin immunoprecipitation analysis to identify regulatory elements in peripheral myelin genes. These techniques have been combined with novel genomics tools (ChIP-chip and ChIP-Seq) to characterize genetic/epigenetic mechanisms of development and how these mechanisms are altered in disorders affecting myelination.
We initially started work on inherited peripheral myelinopathies, since several human EGR2 mutations were identified that cause myelination disorders of the peripheral nervous system such as Congenital Hypomyelinating Neuropathy (CHN), Charcot-Marie-Tooth Disease (CMT), and Dejerine-Sottas Syndrome (DSS). Association of EGR2 mutations with such myelination disorders is consistent with mouse studies showing that EGR2 regulates a diverse array of myelin-associated genes. Finally, we have been engaged in identifying regulatory elements in the human PMP22 gene, in order to elucidate its regulation, and to develop novel therapeutic strategies to treat Charcot-Marie-Tooth (CMT) disease. These studies have lead to creation of drug screening assays that are being used to identify candidate compounds for treatment of CMT1A .
- Course Coordinator for Molecular and Metabolic Basis of Medicine
Director, Waisman Center Cellular and Molecular Neuroscience Core
- Program in Cellular and Molecular Biology
- Molecular Biosciences Training Grant
- Molecular and Cellular Pharmacology Program
- Comparative Biomedical Sciences Graduate Program
Srinivasan, R., Sun, G., Keles, S., Jones, E.A., Jang, S.W., Krueger, C., and Svaren, J. (2012) Genome-wide analysis of EGR2/SOX10 binding in myelinating peripheral nerve, Nucleic Acids Research, 40:6449-6460 PMC3413122
Hung, H.A., Kohnken, R., and Svaren, J. (2012) The NURD chromatin remodeling complex is required for peripheral nerve myelination, Journal of Neuroscience, 32(5):1517-27 PMC3292862
Jones, E.A., Brewer, M.H., Srinivasan, R., Krueger, C., Sun, G., Charney, K.N., Keles, S., Antonellis, A., Svaren, J. (2012) Distal enhancers upstream of the Charcot-Marie-Tooth type 1A disease gene PMP22, Human Molecular Genetics, 21(7):1581-91 PMC3298281
Gokey, N.G., Srinivasan, R., Lopez-Anido, C., Krueger, C., Svaren, J. (2012) Developmental Regulation of MicroRNA Expression in Schwann Cells, Molecular and Cellular Biology, 32:558-568 PMC3255778
Jones, E.A., Lopez-Anido, C., Srinivasan, R., Krueger, C., Chang, L.W., Nagarajan, R., and Svaren, J. (2011) Regulation of the PMP22 gene through an intronic enhancer, Journal of Neuroscience, 31:4242-4250. PMC3100536