Oregon State University
Dorina Avram's research program is in the field of immune system regulation. This lab is interested in alterations of immune regulatory mechanisms associated with autoimmune diseases, particularly inflammatory bowel disease and multiple sclerosis. One research area is in the transcriptional control of T cell function with main emphasis on the transcription factor Bcl11b, which Dr. Avram discovered when she was a postdoc with Dr. Mark Leid. Using conditional and inducible knockout mouse models, Avram lab found that Bcl11b plays a crucial role in T cell development, as well as in mature T cells, including CD8+ T cells, iNKT cells and T regulatory cells. At molecular level, Avram lab demonstrated that Bcl11b functions both as a transcriptional repressor, through association with the transcriptional corepressor complex NuRD, and as a transcriptional activator, through association with transcriptional coactivator complexes containing CBP/p300 HATs. Avram lab continues to investigate the role of Bcl11b in T cells, using conditional and inducible deletion of the gene in mice, as well as transgenic mouse models, and in vitro cellular systems. Specific directions of this area of research are: (1) determining the role of Bcl11b in Thelper cells, NKT, T regulatory and innate lymphoid cells, and how alterations in Bcl11b function result in immune disorders; (2) understanding the switch signals that confer to Bcl11b transcriptional activation versus transcriptional repression function, and their implications on expression of networks of genes; (3) understanding how Bcl11b cooperates or competes with other lineage specific transcription factors and regulatory complexes to control common genes or stage specific genes.
Other areas of research recently initiated include regulation of Thelper function by ubiquitination and implication in autoimmune disorders, as well as transcriptional control in immune lineage development by Mef2 transcription factors.
- Uddin MN, Zhang Y, Harton JA, MacNamara KC, Avram D. (2014) TNF-?-dependent hematopoiesis following Bcl11b deletion in T cells restricts metastatic melanoma. J Immunol. 2014 Feb 15;192(4):1946-53
- Califano D, Sweeney KJ, Le H, VanValkenburgh J, Yager E, O'Connor W Jr, Kennedy JS, Jones DM, Avram D. (2014) Diverting T helper cell trafficking through increased plasticity attenuates autoimmune encephalomyelitis. J Clin Invest. 2014 Jan 2;124(1):174-87
- Van Valkenburgh J, Albu DI, Bapanpally C, Casanova S, Califano D, Jones DM, Ignatowicz L, Kawamoto D, Fagarasan S, Jenkins NA, Copeland NG, Liu P, Avram D. (2011) Critical role of Bcl11b in suppressor function of T regulatory cells and prevention of inflammatory bowel disease. J. Exp. Med. 208(10):2069-2081.
- Albu Di, Van Valkenburg J, Morin N, Califano D, Jenkins NA, Copeland NG, Liu P, Avram D. (2011) Transcription factor Bcl11b controls selection of invariant natural killer T-cells by regulating glycolipid presentation in double-positive thymocytes. Proc. Natl. Acad. Sci. USA 108(15):6211-6216.
- Zhang S, Rozell M, Verma RK, Albu DI, Califano D, Van Valkenburgh J, Merchant A, Rangel-Moreno J. Randall TD, Jenkins NA, Copeland NG, Liu P, Avram D. (2010) Antigen-specific clonal expansion and cytolytic effector function of CD8+ T lympocytes depend on the transcription factor Bcl11B. J. Exp. Med. 207(8):1687-1699.
- Albu DI, Feng D, Bhattacharya D, Jenkins NA, Copeland NG, Liu P, Avram D. (2007) BCL11B is required for positive selection and survival of double-positive thymocytes. J. Exp. Med. 204:3003-3015.
- Cismasiu VB, Ghanta S, Duque J, Albu DI, Chen HM, Kasturi R, Avram D. (2006) BCL11B participates in the activation of IL2 gene expression in CD4+ T lymphocytes. Blood 108(8):2695-2702.
- Cismasiu VB, Adamo K, Gecewicz J, Duque J, Lin Q, Avram D. (2005) BCL11B functionally associates with the NuRD complex in T lymphocytes to repress targeted promoter. Oncogene 24(45):6753-6764.