Our laboratory is focused on the transcriptional and epigenetic regulation of myelination. Myelin is a vital constituent of the nervous system that increases the speed of action potentials, and also provides trophic support for the long axons that project from neurons. Our studies are centered on the myelin-producing cells of the peripheral nervous system, and the picture below shows a Schwann cell that has synthesized a myelin sheath around the axon to the left. We have focused on elucidating gene regulation of individual myelin genes by two major regulators of Schwann cell function: Egr2 and Sox10. Sox10 is required at virtually all phases of Schwann cell development and Egr2 is required for initation of myelination. For example, we have recently characterized enhancers within the Pmp22 gene, which is duplicated in the most common form of Charcot-Marie-Tooth Disease, classified as CMT1A. These studies are also developing novel screening assays to identify drugs that could be used for this very common peripheral neuropathy.
Honors & Awards
- Pfizer Animal Health Research Excellence Award, 2009
- Muscular Dystrophy Association Development Grant, 1999
- National Institutes of Health Postdoctoral Fellowship, 1995
- National Science Foundation-North Atlantic Treat Organization (NSF-NATO) Postdoctoral Fellowship, 1993
- Post-doctoral Fellowship from the National Science Foundation, Program for Medium and Long Term Research at Foreign Centers of Excellence, 1992
- Inglese J, Dranchak P, Moran JJ, Jang SW, Srinivasan R, et al. Genome editing-enabled HTS assays expand drug target pathways for Charcot-Marie-tooth disease. ACS Chem Biol. 2014 Nov 21;9(11):2594-602. PubMed PMID: 25188731; PubMed Central PMCID: PMC4245164.
- Hung HA, Sun G, Keles S, Svaren J. Dynamic Regulation of Schwann Cell Enhancers after Peripheral Nerve Injury. J Biol Chem. 2015 Jan 22;PubMed PMID: 25614629.
- Lopez-Anido, C., Sun, G., Koenning, M., Srinivasan, R., Hung, H.A., Emery, B., Keles, S., Svaren, J. Differential Sox10 Genomic Occupancy in Myelinating Glia, Glia 2015 in press, NIHMSID684972 PMID 25974668
- Ma, K.H., Hung, H.A. Srinivasan, R., Xie, H., Orkin, S.H., Svaren, J. Regulation of peripheral nerve myelin maintenance by gene repression through Polycomb Repressive Complex 2, J. Neuroscience 2015 35:8640-52 PMID: 26041929
- Srinivasan R, Sun G, Keles S, Jones EA, Jang SW, et al. Genome-wide analysis of EGR2/SOX10 binding in myelinating peripheral nerve. Nucleic Acids Res. 2012 Aug;40(14):6449-60. PubMed PMID: 22492709; PubMed Central PMCID: PMC3413122.