Faculty: Avtar Roopra, PhD
|Dept:||Associate Professor, Neuroscience|
|Contact:|| 5675 MSC
1300 University Ave
|Training Areas:||Molecular and Cellular Pharmacology
|Lab website:||Click Here|
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.
- Pandi G, Nakka VP, Dharap A, Roopra A, and Vemuganti R (2013). MicroRNA miR-29c down-regulation leading to de-repression of its target DNA methyltransferase 3a promotes ischemic brain damage. PLoS One. 8:e58039. Epub 2013 Mar 13.
- Roopra A, Dingledine R, and Hsieh J (2012). Epigenetics and epilepsy. Epilepsia. 53 Suppl 9:2-10. Review. PMID: 23216574
- Wagoner MP and Roopra A (2012). A REST derived gene signature stratifies glioblastomas into chemotherapy resistant and responsive disease. BMC Genomics. 13:686. PMID: 23216891
- Squirrell JM, Fong JJ, Ariza CA, Mael A, Meyer K, Shevde NK, Roopra A, Lyons GE, Kamp TJ, Eliceiri KW, and Ogle BM (2012). Endogenous fluorescence signatures in living pluripotent stem cells change with loss of potency. PLoS One. 7:e43708. Epub 2012 Aug 29. PMID: 22952742
- Ryan SD, Britigan EM, Zasadil LM, Witte K, Audhya A, Roopra A, and Weaver BA (2012). Up-regulation of the mitotic checkpoint component Mad1 causes chromosomal instability and resistance to microtubule poisons. Proc Natl Acad Sci U S A. 109:E2205-14. Epub 2012 Jul 9. PMID: 22778409
- Gunsalus KT, Wagoner MP, Meyer K, Potter WB, Schoenike B, Kim S, Alexander CM, Friedl A, band Roopra A (2012). Induction of the RNA regulator LIN28A is required for the growth and pathogenesis of RESTless breast tumors. Cancer Res. 72:3207-16. Epub 2012 Apr 24. PMID: 22532168
- Kim S, Roopra A, and Alexander CM (2012). A phenotypic mouse model of basaloid breast tumors. PLoS One. 7:e30979. Epub 2012 Feb 9. PMID: 22347416
- Wagoner MP, Gunsalus KT, Schoenike B, Richardson AL, Friedl A, and Roopra A (2010). The transcription factor REST is lost in aggressive breast cancer. PLoS Genet. 6:e1000979. PMID: 20548947
- Potter WB, O'Riordan KJ, Barnett D, Osting SM, Wagoner M, Burger C, and Roopra A (2010). Metabolic regulation of neuronal plasticity by the energy sensor AMPK. PLoS One. 5:e8996. PMID: 20126541
- Stafstrom CE, Ockuly JC, Murphree L, Valley MT, Roopra A, and Sutula TP (2009). Anticonvulsant and antiepileptic actions of 2-deoxy-D-glucose in epilepsy models. Ann Neurol. 65:435-47. PMID: 19399874
- Stafstrom CE, Roopra A, and Sutula TP (2008). Seizure suppression via glycolysis inhibition with 2-deoxy-D-glucose (2DG). Epilepsia. 49 Suppl 8:97-100. Review. PMID: 19049601