Home > Program Faculty >John Svaren Laboratory
The Svaren laboratory studies regulation of gene expression by the Egr (early growth response) family of transcription factors. These zinc finger proteins were originally identified as immediate early genes that become induced by extracellular stimuli, such asgrowth factors, hypoxia, and neuronal activity. Recent knockout analysis of these genes (Egr1, Egr2, Egr3, and Egr4) has confirmed that their physiological role is to respond to environmental changes by modulating transcription of networks of genes.
Recently, several groups have demonstrated that Egr1 plays a key role in mediating induction of the IGF-II and Tissue Factor genes by hypoxia. Furthermore, other data implicating Egr1 in the regulation of hippocampal synaptic plasticity suggest that Egr1 and related factors might also play a key role in plasticity induced by hypoxia.
Dr. Svaren's experience in the analysis of gene expression patterns using both quantitative PCR and microarray techniques will allow investigations of the role played by Egr1 in hypoxic signaling, and a subsequent analysis of the genetic network regulated in this pathway.
Svaren, J., Ehrig, T., Abdulkadir, S.A., Ehrengruber, M.U., Watson, M.A., and Milbrandt, J. (2000) EGR1 Target Genes in Prostate Carcinoma Cells Identified by Microarray Analysis. Journal of Biological Chemistry 275:38524-38531.[Abstract]
Nagarajan, R., Svaren, J., Le, N., Araki T., Watson, M., and Milbrandt, J. (2001) EGR2 mutations in inherited neuropathies dominant negatively inhibit myelin gene expression. Neuron 30:355-368. [Abstract]
Gillian-Daniel, A.L. and Svaren, J. (2004) The Ddx20/DP103 Dead Box Protein Represses Transcriptional Activation by Egr2/Krox-20, Journal of Biological Chemistry 279:9056-63 [Abstract]
LeBlanc, S.E., Srinivasan, R., Ferri, C., Mager, G.M., Gillian-Daniel, A.L., Wrabetz, L., and Svaren, J. (2005) Regulation of lipid/cholesterol biosynthetic genes by Egr2/Krox-20 and the SREBP pathway during peripheral nerve myelination, Journal of Neurochemistry 93:737-748. [Abstract]
LeBlanc, S.E., Jang, S.W., Ward, R.M., Wrabetz, L., and Svaren, J. (2006) Direct Regulation of Myelin Protein Zero Expression by the Egr2 Transactivator, Journal of Biological Chemistry 281:5453-5460 [Abstract]
Srinivasan, R., Mager, G.M., Ward, R.M., Mayer, J., and Svaren, J. (2006) The NAB2 Corepressor Interacts with the CHD4 Subunit of the NuRD Complex, Journal of Biological Chemistry 281:15129-15137 [Abstract]
Jang, S.W., LeBlanc, S.E., Roopra, A., Wrabetz, L., and Svaren, J. (2006) In Vivo Detection of Egr2 Binding to Target Genes during Peripheral Nerve Myelination, Journal of Neurochemistry 98:1678-1687 [Abstract]
LeBlanc, S.E., Ward, R.M., and Svaren, J. (2007) Neuropathy-associated Egr2 Mutants Disrupt Cooperative Activation of Myelin Protein Zero by Egr2 and Sox10, Molecular and Cellular Biology, 27:3251-3259 [Abstract]
Grants
2 RO1 HD 41590
Dr. J. Svaren (PI)1/15/2002-4/30/2012
Genetic control of myelination by EGR2 and NAB proteins
The goals of this grant are to elucidate how molecular interactions of EGR2 with other transcriptional regulators control gene expression in myelinating Schwann cells.
W81XWH-06-1-0167
Dr. J. Svaren (PI)12/1/05-11/30/07
DOD Prostate Cancer Research Program Idea Development Award: Regulation of Egr1 target genes by the NuRD chromatin remodeling complex.
The study investigates the role of the Nucleosome Remodeling/Deacetylase Complex in regulation of EGR1 target genes in prostate cancer by the NAB2 corepressor.0650102Z
Dr. Svaren (PI)7/1/06-6/30/08
American Heart Association Grant-in-Aid
Regulation of cholesterol biosynthesis by EGR transactivators
MDA4249
Dr. Svaren (PI)1/1/07-12/31/08
Muscular Dystrophy Association
Peripheral Neuropathy Protein Interaction Network
This project involves creation of a protein interaction (Y2H) library from different developmental stages of peripheral nerve myelination, which will be screened with genes affected by neuropathy-associated mutations.For assistance with accessibility issues, please click here
Updated 06/29/2007