John Svaren, Phd
Professor, Comparative Biosciences
1500 Highland Ave
- Lab Website
- The Svaren Lab
Our laboratory is devoted to research on transcriptional and epigenomic regulation of myelination and pathogenesis/treatment of peripheral neuropathies. I have a long standing interest in the interplay of chromatin structure and gene regulation, and we were the first to develop chromatin immunoprecipitation analysis to identify regulatory elements in myelin-associated genes in vivo. These techniques have been combined with novel genomics tools (ChIP-Seq) to characterize genetic/epigenetic mechanisms of myelin formation and how these mechanisms are altered in disorders affecting myelination. These tools have been applied to study the role of Sox10 and associated transcription factors in myelin gene networks in both the peripheral and central nervous systems, and we have also profiled repressive and active histone modifications in peripheral nerve. In addition, we have also identified how several microRNAs are regulated by Sox10 during Schwann cell development. More recently, we have investigated the role of epigenomic changes in the dynamic reprogramming Schwann cells after nerve injury, as Schwann cells are a major determinant in the ultimate regeneration and remyelination of axons after nerve injury. Our studies have explored the role of the NuRD complex in Schwann cell development, and we also identified the polycomb pathway as an important regulator of many nerve injury genes.
Our studies also include translational projects as we have been engaged in identifying regulatory elements in the human PMP22 gene, which is duplicated in one of the most common forms of the peripheral neuropathy known as Charcot-Marie-Tooth disease. This type of developmental disability is one of the most common inherited disorders in the nervous system. Our studies have provided novel drug screening assays that are being used to develop novel therapeutic strategies to treat Charcot-Marie-Tooth disease. In addition, our initiatives provide a test case for translational efforts for other gene dosage disorders affecting myelination.
Honors & Awards
- 2016 – Director, Waisman Center Cellular and Molecular Neuroscience Core Director, Waisman Center IDD Models Core
- 2015 – Member, NIH Cellular and Molecular Biology of Glia Study Section
- 2011 – appointed Board Member, and Chair, Scientific Advisory Board, Charcot-Marie-Tooth Association
- 2009 – Pfizer Animal Health Research Excellence Award
- Lopez-Anido C, Poitelon Y, Gopinath C, Moran J, Ma KH, Law WD, Antonellis A, Feltri ML, Svaren J. Tead1regulates the expression of Peripheral myelin protein 22 (Pmp22) during Schwann cell development, 2016 Hum Mol Genet. 25(14):3055-3069 PMID: 27288457
- Ma, KH, Hung, HA, Svaren, J Epigenomic Regulation of Schwann Cell Reprogramming in Peripheral Nerve Injury, J. Neuroscience 2016 36(35):9135-47 PubMed PMID: 27581455 PMC Journal in process
- 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