Faculty: Avtar Roopra, PhD
|Dept:||Associate Professor, Neuroscience|
|Contact:|| 5507 WIMR
1111 Highland Avenue
|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.
- Potter WB, Basu T, O'Riordan KJ, Kirchner A, Rutecki P, Burger C,Roopra A. (2013) Reduced juvenile long-term depression in tuberous sclerosis complex is mitigated in adults by compensatory recruitment of mGluR5 and Erk signaling. http://www.ncbi.nlm.nih.gov/pubmed/23966835 PLoS Biol. 11:e1001627. Epub 2013 Aug 13. PMID: 23966835 [PubMed - indexed for MEDLINE]
- Elgamal OA, Park JK, Gusev Y, Azevedo-Pouly AC, Jiang J,Roopra A, Schmittgen TD. (2013) Tumor suppressive function of mir-205 in breast cancer is linked to HMGB3 regulation. PLoS One. 8(10):e76402. doi: eCollection 2013. PMID: 24098490 [PubMed - in process]
- 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