Avtar Roopra

Research Strength: Molecular Neuroscience

Controlling Expression of Neuronal Genes by the Transcription Factor NRSF

The lab's over-arching goal is to understand the epigenetic mechanisms behind transcriptional regulation and chromatin structure in mammals. A major focus is the study of mechanisms that regulate the expression of neuronal target genes. We have shown that the transcription factor NRSF recruits a number of chromatin modifying complexes that include histone deacetylases and methylases. Also, we have found that NRSF uses a metabolism-sensing co-repressor to repress expression of genes involved in nervous system function as well as tumor metastasis. Based on these findings, we have been able to control genes important for the progression of epilepsy in vivo by the use of small molecule inhibitors of glycolysis. This treatment resulted in suppression of epileptogenesis in rodent models of epilepsy and our small molecule inhibitors of energy metabolism will be entering clinical trials for epilepsy in the coming months. Many genes regulated by NRSF are implicated in metastasis. As such we are pursuing the possibility of controlling genes important for cancer progression using small molecule regulators of energy metabolism. These projects span both neuroscience and cancer biology and have generated compounds that can go into clinical trials for neurological disorders and metastasis prevention.

Lab Website:

http://www.neurology.wisc.edu/roopra.html

Selected Publications:

Garriga-Canut, M., B. Schoenike, R. Qazi, K. Bergendahl, T.J. Daley, R.M. Pfender, J.F. Morrison, J. Ockuly, C. Stafstrom, T. Sutula, and A. Roopra. 2006. Epilepsy progression is reduced by 2-deoxy-D-glucose and is associated with NRSF-CtBP dependent metabolic regulation of chromatin structure. Nat. Neuroscience. 9:1382-7. [PDF]
Roopra, A., R. Qazi, B. Schoenike, T.J. Daley, J.F. Morrison. 2004. Localized domains of G9a mediated histone methylation are required for silencing of neuronal genes. Mol. Cell. 14: 727-738. [PDF]
Roopra, A., Y. Huang, and R. Dingledine. 2001. Neurological disease: Listening to silencers. Mol. Interv. 14: 219-228. [PDF]


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Avtar Roopra E-mail: roopra@neurology.wisc.edu Research Strength: Molecular Neuroscience Controlling Expression of Neuronal Genes by the Transcription Factor NRSF The lab's over-arching goal is to understand the epigenetic mechanisms behind transcriptional regulation and chromatin structure in mammals. A major focus is the study of mechanisms that regulate the expression of neuronal target genes. We have shown that the transcription factor NRSF recruits a number of chromatin modifying complexes that include histone deacetylases and methylases. Also, we have found that NRSF uses a metabolism-sensing co-repressor to repress expression of genes involved in nervous system function as well as tumor metastasis. Based on these findings, we have been able to control genes important for the progression of epilepsy in vivo by the use of small molecule inhibitors of glycolysis. This treatment resulted in suppression of epileptogenesis in rodent models of epilepsy and our small molecule inhibitors of energy metabolism will be entering clinical trials for epilepsy in the coming months. Many genes regulated by NRSF are implicated in metastasis. As such we are pursuing the possibility of controlling genes important for cancer progression using small molecule regulators of energy metabolism. These projects span both neuroscience and cancer biology and have generated compounds that can go into clinical trials for neurological disorders and metastasis prevention. Lab Website: http://www.neurology.wisc.edu/roopra.html Selected Publications: Garriga-Canut, M., B. Schoenike, R. Qazi, K. Bergendahl, T.J. Daley, R.M. Pfender, J.F. Morrison, J. Ockuly, C. Stafstrom, T. Sutula, and A. Roopra. 2006. Epilepsy progression is reduced by 2-deoxy-D-glucose and is associated with NRSF-CtBP dependent metabolic regulation of chromatin structure. Nat. Neuroscience. 9:1382-7. [PDF] Roopra, A., R. Qazi, B. Schoenike, T.J. Daley, J.F. Morrison. 2004. Localized domains of G9a mediated histone methylation are required for silencing of neuronal genes. Mol. Cell. 14: 727-738. [PDF] Roopra, A., Y. Huang, and R. Dingledine. 2001. Neurological disease: Listening to silencers. Mol. Interv. 14: 219-228. [PDF]

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