Faculty: Avtar Roopra
|Dept:||Associate Professor, Neuroscience|
|Training Areas:||Molecular & Cellular Pharmacology|
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.
Honors & Awards
- Not available
Other Positions & Affiliations
- Not available
- Roopra A, Dingledine R, Hsieh J. Epigenetics and epilepsy. Epilepsia. 2012 Dec;53 Suppl 9:2-10. doi: 10.1111/epi.12030. Review. PMID: 23216574
- Wagoner MP, Roopra A. A REST derived gene signature stratifies glioblastomas into chemotherapy resistant and responsive disease. BMC Genomics. 2012 Dec 7;13:686. doi: 10.1186/1471-2164-13-686. PMID: 23216891
- Squirrell JM, Fong JJ, Ariza CA, Mael A, Meyer K, Shevde NK, Roopra A, Lyons GE, Kamp TJ, Eliceiri KW, Ogle BM. Endogenous fluorescence signatures in living pluripotent stem cells change with loss of potency. PLoS One. 2012;7(8):e43708. doi: 10.1371/journal.pone.0043708. Epub 2012 Aug 29. PMID: 22952742
- Ryan SD, Britigan EM, Zasadil LM, Witte K, Audhya A, Roopra A, Weaver BA. Up-regulation of the mitotic checkpoint component Mad1 causes chromosomal instability and resistance to microtubule poisons. Proc Natl Acad Sci U S A. 2012 Aug 14;109(33):E2205-14. doi: 10.1073/pnas.1201911109. Epub 2012 Jul 9. PMID: 22778409
- Gunsalus KT, Wagoner MP, Meyer K, Potter WB, Schoenike B, Kim S, Alexander CM, Friedl A, Roopra A. Induction of the RNA regulator LIN28A is required for the growth and pathogenesis of RESTless breast tumors. Cancer Res. 2012 Jul 1;72(13):3207-16. doi: 10.1158/0008-5472.CAN-11-1639. Epub 2012 Apr 24. PMID: 22532168
- Kim S, Roopra A, Alexander CM. A phenotypic mouse model of basaloid breast tumors. PLoS One. 2012;7(2):e30979. doi: 10.1371/journal.pone.0030979. Epub 2012 Feb 9. PMID: 22347416
- Wagoner MP, Gunsalus KT, Schoenike B, Richardson AL, Friedl A, Roopra A (2010). The transcription factor REST is lost in aggressive breast cancer. PLoS Genet. 6(6):e1000979. PMID: 20548947
- Potter WB, O'Riordan KJ, Barnett D, Osting SM, Wagoner M, Burger C, Roopra A (2010). Metabolic regulation of neuronal plasticity by the energy sensor AMPK. PLoS One. 5(2):e8996. PMID: 20126541
- Stafstrom CE, Ockuly JC, Murphree L, Valley MT, Roopra A, Sutula TP (2009). Anticonvulsant and antiepileptic actions of 2-deoxy-D-glucose in epilepsy models. Ann Neurol. 65(4):435-47. PMID: 19399874
- Stafstrom CE, Roopra A, Sutula TP (2008). Seizure suppression via glycolysis inhibition with 2-deoxy-D-glucose (2DG). Epilepsia.49 Suppl 8:97-100. Review. PMID: 19049601