John Svaren, PhD

Portrait of John Svaren, PhD
Professor
Comparative Biosciences
Address: 
661 Waisman Center
1500 Highland Avenue
Madison, WI 53705
Telephone: 
(608) 263-4246
Focus Groups: 
Signal Transduction
Education: 
PhD, Molecular Physiology, Vanderbilt University, Nashville, TN
Research Summary: 
Regulation of peripheral nerve myelination by transcription and epigenomic control; Drug discovery for Charcot-Marie-Tooth Disease
Research Detail: 

Our laboratory is devoted to research on transcriptional and epigenomic regulation of myelination and pathogenesis/treatment of peripheral neuropathies. We 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.

We are also extending our molecular analyses of gene regulation to the analysis of CNS myelination by oligodendroctyes. These tools were applied to study the comparative role of Sox10 and associated transcription factors in myelin maturation in both the peripheral and central nervous systems, and our genomic studies also helped identify the causative mutant gene in a rat model of hypomyelination, known as taiep.

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.

Selected Publications: 
Regulation of the neuropathy-associated Pmp22 gene by a distal super-enhancer.Pantera H, Moran JJ, Hung HA, Pak E, Dutra A, Svaren J.Hum Mol Genet. 2018 May 16. doi: 10.1093/hmg/ddy191. [Epub ahead of print]PMID: 29771329
Myelin protein zero mutations and the unfolded protein response in Charcot Marie Tooth disease type 1B.Bai Y, Wu X, Brennan KM, Wang DS, D'Antonio M, Moran J, Svaren J, Shy ME.Ann Clin Transl Neurol. 2018 Mar 10;5(4):445-455. doi: 10.1002/acn3.543. eCollection 2018 Apr.PMID: 29687021
Genome-Edited Cell Lines for High-Throughput Screening.Dranchak P, Moran JJ, MacArthur R, Lopez-Anido C, Inglese J, Svaren J.Methods Mol Biol. 2018;1755:1-17. doi: 10.1007/978-1-4939-7724-6_1.PMID: 29671259
Egr2-dependent microRNA-138is dispensable for peripheral nerve myelination.Lin HP, Oksuz I, Svaren J, Awatramani R.Sci Rep. 2018 Feb 28;8(1):3817. doi: 10.1038/s41598-018-22010-8.PMID: 29491350
Cell transplantation strategies for acquired and inherited disorders of peripheral myelin.Muhammad AKMG, Kim K, Epifantseva I, Aghamaleky-Sarvestany A, Simpkinson ME, Carmona S, LanderosJ, Bell S, Svaren J, Baloh RH.Ann Clin Transl Neurol. 2018 Jan 22;5(2):186-200. doi: 10.1002/acn3.517. eCollection 2018 Feb.PMID: 29468179
EpigeneticControl of Schwann Cells.Ma KH, Svaren J.Neuroscientist. 2018 Jan 1:1073858417751112. doi: 10.1177/1073858417751112. [Epub ahead of print]PMID: 29307265
PMP22 antisense oligonucleotides reverse Charcot-Marie-Tooth disease type 1A features in rodent models.Zhao HT, Damle S, Ikeda-Lee K, Kuntz S, Li J, Mohan A, Kim A, Hung G, Scheideler MA, Scherer SS, SvarenJ, Swayze EE, Kordasiewicz HB.J Clin Invest. 2018 Jan 2;128(1):359-368. doi: 10.1172/JCI96499. Epub 2017 Dec 4.PMID: 29202483
A mutation in the Tubb4a gene leads to microtubule accumulation with hypomyelination and demyelination.Duncan ID, Bugiani M, Radcliff AB, Moran JJ, Lopez-Anido C, Duong P, August BK, Wolf NI, van der Knaap MS, Svaren J.Ann Neurol. 2017 May;81(5):690-702. doi: 10.1002/ana.24930. Epub 2017 May 9.PMID: 28393430
Epigenomic reprogramming in peripheral nerve injury.Ma KH, Svaren J.Neural Regen Res. 2016 Dec;11(12):1930-1931. doi: 10.4103/1673-5374.197133. No abstract available.PMID: 28197188
Dual specificity phosphatase 15 regulates Erk activation in Schwann cells.Rodríguez-Molina JF, Lopez-Anido C, Ma KH, Zhang C, Olson T, Muth KN, Weider M, Svaren J.J Neurochem. 2017 Feb;140(3):368-382. doi: 10.1111/jnc.13911. Epub 2017 Jan 9.PMID: 27891578