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Dorina Avram, PhD

Academic Rank: Senior Member

Overview

Dorina Avram conducted her PhD studies in yeast genetics at Oregon State University and then she trained as a postdoc in the laboratory of Mark Leid working on a family of ligand-binding transcription factors known as nuclear receptors. In Mark Leid’s lab she discovered a family of transcription factors, initially known as CTIP1 and CTIP2, and later as BCL11A and BCL11B. These two transcription factors function both as DNA-binding proteins, as well as mediators of repression function of other transcription factors, such as the COUP-TF family of orphan nuclear receptors. Starting her independent career in 2002, Dorina Avram decided to focus on the role of BCL11B in immune system, initially on biochemistry and the link of this transcription factor and the related BCL11A to oncogenesis, being funded by the American Cancer Society and by NIH through a KO1 developmental award. She continued to dissect the biology of BCL11B in immune system and has been funded by multiple NIH RO1 grants since 2007. Her lab established the critical and complex roles of this fascinating transcription factor in essential immune T cells populations, including in Tregulatory cells, iNKT cells, mature CD4+ and CD8+ T cells and in innate lymphoid cells. Avram’s lab has investigated Bcl11b’s role in the context of the network of transcription factors and epigenetic regulators that control the response of these cells during immune response to infections, in tumors and in autoimmunity and their studies were published in the Journal of Experimental Medicine, Immunity, Nature Communications, Science Advances, PNAS, Journal of Clinical Investigation, Blood, Oncogene and in the Journal of Immunology. Another direction of research in Avram’s lab is the investigation of the regulatory roles of ubiquitin ligases in autoimmunity, inflammation and cancer. Of special interest are ubiquitin ligases which target for signaling tumor suppressors and oncogenes.


Discipline

    • Immunology
    • Immunology

Education & Training

Fellowship:

  • Oregon State University, Corvallis, PhD - Genetics
  • Oregon State University, -
  • Oregon State University, - Molecular Pharmacology
Research

Dr. Avram has two major research interests: (1) Transcriptional and epigenetic control of immune cells in tumors and in infection, and (2) ubiquitination in inflammation and cancer, both with the goal of harnessing the immune responses for cancer therapies.

Publications

  • Kwiatkowski AJ, Stewart JM, Cho JJ, Avram D, Keselowsky BG. Nano and Microparticle Emerging Strategies for Treatment of Autoimmune Diseases: Multiple Sclerosis and Type 1 Diabetes. Adv Healthc Mater. 2020 Jun.9(11):e2000164. Pubmedid: 32519501.
  • Fu Z, Ye J, Dean JW, Bostick JW, Weinberg SE, Xiong L, Oliff KN, Chen ZE, Avram D, Chandel NS, Zhou L. Requirement of Mitochondrial Transcription Factor A in Tissue-Resident Regulatory T Cell Maintenance and Function. Cell Rep. 2019 Jul.28(1):159-171.e4. Pubmedid: 31269437. Pmcid: PMC6679941.
  • Cho JJ, Xu Z, Parthasarathy U, Drashansky TT, Helm EY, Zuniga AN, Lorentsen KJ, Mansouri S, Cho JY, Edelmann MJ, Duong DM, Gehring T, Seeholzer T, Krappmann D, Uddin MN, Califano D, Wang RL, Jin L, Li H, Lv D, Zhou D, Zhou L, Avram D. Hectd3 promotes pathogenic Th17 lineage through Stat3 activation and Malt1 signaling in neuroinflammation. Nat Commun. 2019 Feb.10(1):701. Pubmedid: 30741923. Pmcid: PMC6370850.
  • Drashansky TT, Helm E, Huo Z, Curkovic N, Kumar P, Luo X, Parthasarathy U, Zuniga A, Cho JJ, Lorentsen KJ, Xu Z, Uddin M, Moshkani S, Zhou L, Avram D. Bcl11b prevents fatal autoimmunity by promoting Treg cell program and constraining innate lineages in Treg cells. Sci Adv. 2019 Aug.5(8):eaaw0480. Pubmedid: 31457080. Pmcid: PMC6685710.
  • Sun X, Winglee K, Gharaibeh RZ, Gauthier J, He Z, Tripathi P, Avram D, Bruner S, Fodor A, Jobin C. Microbiota-Derived Metabolic Factors Reduce Campylobacteriosis in Mice. Gastroenterology. 2018 May.154(6):1751-1763.e2. Pubmedid: 29408609. Pmcid: PMC5927838.
  • Califano D, Furuya Y, Roberts S, Avram D, McKenzie ANJ, Metzger DW. IFN-γ increases susceptibility to influenza A infection through suppression of group II innate lymphoid cells. Mucosal Immunol. 2018 Jan.11(1):209-219. Pubmedid: 28513592. Pmcid: PMC5693789.
  • Bryant AJ, Shenoy V, Fu C, Marek G, Lorentsen KJ, Herzog EL, Brantly ML, Avram D, Scott EW. Myeloid-derived Suppressor Cells Are Necessary for Development of Pulmonary Hypertension. Am J Respir Cell Mol Biol. 2018 Feb.58(2):170-180. Pubmedid: 28862882. Pmcid: PMC5805999.
  • Lorentsen KJ, Cho JJ, Luo X, Zuniga AN, Urban JF, Zhou L, Gharaibeh R, Jobin C, Kladde MP, Avram D. Bcl11b is essential for licensing Th2 differentiation during helminth infection and allergic asthma. Nat Commun. 2018 Apr.9(1):1679. Pubmedid: 29700302. Pmcid: PMC5920086.
  • Li S, Bostick JW, Ye J, Qiu J, Zhang B, Urban JF, Avram D, Zhou L. Aryl Hydrocarbon Receptor Signaling Cell Intrinsically Inhibits Intestinal Group 2 Innate Lymphoid Cell Function. Immunity. 2018 11.49(5):915-928.e5. Pubmedid: 30446384. Pmcid: PMC6249058.
  • Cho JJ, Stewart JM, Drashansky TT, Brusko MA, Zuniga AN, Lorentsen KJ, Keselowsky BG, Avram D. An antigen-specific semi-therapeutic treatment with local delivery of tolerogenic factors through a dual-sized microparticle system blocks experimental autoimmune encephalomyelitis. Biomaterials. 2017 Oct.143:79-92. Pubmedid: 28772190. Pmcid: PMC5870833.
  • Sharp SP, Avram D, Stain SC, Lee EC. Local and systemic Th17 immune response associated with advanced stage colon cancer. J Surg Res. 2017 Feb.208:180-186. Pubmedid: 27993206. Pmcid: PMC6086724.
  • Abboud G, Stanfield J, Tahiliani V, Desai P, Hutchinson TE, Lorentsen KJ, Cho JJ, Avram D, Salek-Ardakani S. Transcription Factor Bcl11b Controls Effector and Memory CD8 T cell Fate Decision and Function during Poxvirus Infection. Front Immunol. 2016 Oct.7:425. Pubmedid: 27790219. Pmcid: PMC5061747.
  • Periasamy S, Avram D, McCabe A, MacNamara KC, Sellati TJ, Harton JA. An Immature Myeloid/Myeloid-Suppressor Cell Response Associated with Necrotizing Inflammation Mediates Lethal Pulmonary Tularemia. PLoS Pathog. 2016 Mar.12(3):e1005517. Pubmedid: 27015566. Pmcid: PMC4807818.
  • Uddin MN, Sultana DA, Lorentsen KJ, Cho JJ, Kirst ME, Brantly ML, Califano D, Sant'Angelo DB, Avram D. Transcription factor Bcl11b sustains iNKT1 and iNKT2 cell programs, restricts iNKT17 cell program, and governs iNKT cell survival. Proc Natl Acad Sci U S A. 2016 Jul.113(27):7608-7613. Pubmedid: 27330109. Pmcid: PMC4941433.
  • Califano D, Cho JJ, Uddin MN, Lorentsen KJ, Yang Q, Bhandoola A, Li H, Avram D. Transcription Factor Bcl11b Controls Identity and Function of Mature Type 2 Innate Lymphoid Cells. Immunity. 2015 Aug.43(2):354-368. Pubmedid: 26231117. Pmcid: PMC4657441.
  • Avram D, Califano D. The multifaceted roles of Bcl11b in thymic and peripheral T cells: impact on immune diseases. J Immunol. 2014 Sep.193(5):2059-2065. Pubmedid: 25128552. Pmcid: PMC4135393.
  • Califano D, Sweeney KJ, Le H, VanValkenburgh J, Yager E, O'Connor W, Kennedy JS, Jones DM, Avram D. Diverting T helper cell trafficking through increased plasticity attenuates autoimmune encephalomyelitis. J Clin Invest. 2014 Jan.124(1):174-187. Pubmedid: 24316973. Pmcid: PMC3871236.
  • Uddin MN, Zhang Y, Harton JA, MacNamara KC, Avram D. TNF-α-dependent hematopoiesis following Bcl11b deletion in T cells restricts metastatic melanoma. J Immunol. 2014 Feb.192(4):1946-1953. Pubmedid: 24446520. Pmcid: PMC3946214.
  • Harmon EY, Fronhofer V, Keller RS, Feustel PJ, Zhu X, Xu H, Avram D, Jones DM, Nagarajan S, Lennartz MR. Anti-inflammatory immune skewing is atheroprotective: Apoe−/−FcγRIIb−/− mice develop fibrous carotid plaques. J Am Heart Assoc. 2014 Dec.3(6):e001232. Pubmedid: 25516435. Pmcid: PMC4338708.
  • Zhang Y, Jones M, McCabe A, Winslow GM, Avram D, MacNamara KC. MyD88 signaling in CD4 T cells promotes IFN-γ production and hematopoietic progenitor cell expansion in response to intracellular bacterial infection. J Immunol. 2013 May.190(9):4725-4735. Pubmedid: 23526822. Pmcid: PMC3633622.
  • Bucur O, Almasan A, Nikolajczyk BS, Nicolson GL, Lawler J, Velculescu VE, Draghici S, Leabu M, Avram D, Bucur I, Calautti E, Calin GA, Chauhan SC, Ciubotaru M, Constantinescu SN, Datta D, Duda DG, Friedman MT, Galardy PJ, Harris BT, Huarte M, Khalil AM, Marchetti D, Movileanu L, Nat R, Nucera C, Popa-Wagner A, Stancu AL, Zhu S, Liehn EA. Discoveries: an innovative platform for publishing cutting-edge research discoveries in medicine, biology and chemistry. Discoveries (Craiova). 2013 Dec.1(1):e1. Pubmedid: 32309535. Pmcid: PMC6919543.
  • Vanvalkenburgh J, Albu DI, Bapanpally C, Casanova S, Califano D, Jones DM, Ignatowicz L, Kawamoto S, Fagarasan S, Jenkins NA, Copeland NG, Liu P, Avram D. Critical role of Bcl11b in suppressor function of T regulatory cells and prevention of inflammatory bowel disease. J Exp Med. 2011 Sep.208(10):2069-2081. Pubmedid: 21875956. Pmcid: PMC3182057.
  • Albu DI, VanValkenburgh J, Morin N, Califano D, Jenkins NA, Copeland NG, Liu P, Avram D. Transcription factor Bcl11b controls selection of invariant natural killer T-cells by regulating glycolipid presentation in double-positive thymocytes. Proc Natl Acad Sci U S A. 2011 Apr.108(15):6211-6216. Pubmedid: 21444811. Pmcid: PMC3076841.
  • Albu DI, Califano D, Avram D. Flow cytometry analysis of transcription factors in T lymphocytes. Methods Mol Biol. 2010 May.647:377-390. Pubmedid: 20694680. Pmcid: PMC3788577.
  • Zhang S, Rozell M, Verma RK, Albu DI, Califano D, VanValkenburgh J, Merchant A, Rangel-Moreno J, Randall TD, Jenkins NA, Copeland NG, Liu P, Avram D. Antigen-specific clonal expansion and cytolytic effector function of CD8+ T lymphocytes depend on the transcription factor Bcl11b. J Exp Med. 2010 Aug.207(8):1687-1699. Pubmedid: 20660613. Pmcid: PMC2916134.
  • Cismasiu VB, Duque J, Paskaleva E, Califano D, Ghanta S, Young HA, Avram D. BCL11B enhances TCR/CD28-triggered NF-kappaB activation through up-regulation of Cot kinase gene expression in T-lymphocytes. Biochem J. 2009 Jan.417(2):457-466. Pubmedid: 18831712. Pmcid: PMC2639648.
  • Cismasiu VB, Paskaleva E, Suman Daya S, Canki M, Duus K, Avram D. BCL11B is a general transcriptional repressor of the HIV-1 long terminal repeat in T lymphocytes through recruitment of the NuRD complex. Virology. 2008 Oct.380(2):173-181. Pubmedid: 18768194. Pmcid: PMC2637995.
  • Albu DI, Feng D, Bhattacharya D, Jenkins NA, Copeland NG, Liu P, Avram D. BCL11B is required for positive selection and survival of double-positive thymocytes. J Exp Med. 2007 Nov.204(12):3003-3015. Pubmedid: 17998389. Pmcid: PMC2118514.
  • Cismasiu VB, Ghanta S, Duque J, Albu DI, Chen HM, Kasturi R, Avram D. BCL11B participates in the activation of IL2 gene expression in CD4+ T lymphocytes. Blood. 2006 Oct.108(8):2695-2702. Pubmedid: 16809611. Pmcid: PMC1895584.
  • Cismasiu VB, Adamo K, Gecewicz J, Duque J, Lin Q, Avram D. BCL11B functionally associates with the NuRD complex in T lymphocytes to repress targeted promoter. Oncogene. 2005 Oct.24(45):6753-6764. Pubmedid: 16091750.
  • Amparan D, Avram D, Thomas CG, Lindahl MG, Yang J, Bajaj G, Ishmael JE. Direct interaction of myosin regulatory light chain with the NMDA receptor. J Neurochem. 2005 Jan.92(2):349-361. Pubmedid: 15663482.
  • Leid M, Ishmael JE, Avram D, Shepherd D, Fraulob V, Dollé P. CTIP1 and CTIP2 are differentially expressed during mouse embryogenesis. Gene Expr Patterns. 2004 Oct.4(6):733-739. Pubmedid: 15465497. Pmcid: PMC2819357.
  • Senawong T, Peterson VJ, Avram D, Shepherd DM, Frye RA, Minucci S, Leid M. Involvement of the histone deacetylase SIRT1 in chicken ovalbumin upstream promoter transcription factor (COUP-TF)-interacting protein 2-mediated transcriptional repression. J Biol Chem. 2003 Oct.278(44):43041-43050. Pubmedid: 12930829. Pmcid: PMC2819354.
  • Rohr O, Lecestre D, Chasserot-Golaz S, Marban C, Avram D, Aunis D, Leid M, Schaeffer E. Recruitment of Tat to heterochromatin protein HP1 via interaction with CTIP2 inhibits human immunodeficiency virus type 1 replication in microglial cells. J Virol. 2003 May.77(9):5415-5427. Pubmedid: 12692243. Pmcid: PMC153947.
  • Avram D, Fields A, Senawong T, Topark-Ngarm A, Leid M. COUP-TF (chicken ovalbumin upstream promoter transcription factor)-interacting protein 1 (CTIP1) is a sequence-specific DNA binding protein. Biochem J. 2002 Dec.368(Pt 2):555-563. Pubmedid: 12196208. Pmcid: PMC1223006.
  • Nevrivy DJ, Peterson VJ, Avram D, Ishmael JE, Hansen SG, Dowell P, Hruby DE, Dawson MI, Leid M. Interaction of GRASP, a protein encoded by a novel retinoic acid-induced gene, with members of the cytohesin family of guanine nucleotide exchange factors. J Biol Chem. 2000 Jun.275(22):16827-16836. Pubmedid: 10828067.
  • Avram D, Fields A, Pretty On Top K, Nevrivy DJ, Ishmael JE, Leid M. Isolation of a novel family of C(2)H(2) zinc finger proteins implicated in transcriptional repression mediated by chicken ovalbumin upstream promoter transcription factor (COUP-TF) orphan nuclear receptors. J Biol Chem. 2000 Apr.275(14):10315-10322. Pubmedid: 10744719. Pmcid: PMC2819356.
  • Avram D, Ishmael JE, Nevrivy DJ, Peterson VJ, Lee SH, Dowell P, Leid M. Heterodimeric interactions between chicken ovalbumin upstream promoter-transcription factor family members ARP1 and ear2. J Biol Chem. 1999 May.274(20):14331-14336. Pubmedid: 10318855. Pmcid: PMC2823254.
  • Dowell P, Ishmael JE, Avram D, Peterson VJ, Nevrivy DJ, Leid M. Identification of nuclear receptor corepressor as a peroxisome proliferator-activated receptor alpha interacting protein. J Biol Chem. 1999 May.274(22):15901-15907. Pubmedid: 10336495.
  • Avram D, Leid M, Bakalinsky AT. Fzf1p of Saccharomyces cerevisiae is a positive regulator of SSU1 transcription and its first zinc finger region is required for DNA binding. Yeast. 1999 Apr.15(6):473-480. Pubmedid: 10234785.
  • Bouvier C, Avram D, Peterson VJ, Hettinger B, Soderstrom K, Murray TF, Leid M. Catecholaminergic CATH.a cells express predominantly delta-opioid receptors. Eur J Pharmacol. 1998 May.348(1):85-93. Pubmedid: 9650835.
  • Avram D, Bakalinsky AT. SSU1 encodes a plasma membrane protein with a central role in a network of proteins conferring sulfite tolerance in Saccharomyces cerevisiae. J Bacteriol. 1997 Sep.179(18):5971-5974. Pubmedid: 9294463. Pmcid: PMC179495.
  • Dowell P, Ishmael JE, Avram D, Peterson VJ, Nevrivy DJ, Leid M. p300 functions as a coactivator for the peroxisome proliferator-activated receptor alpha. J Biol Chem. 1997 Dec.272(52):33435-33443. Pubmedid: 9407140.
  • Avram D, Bakalinsky AT. Multicopy FZF1 (SUL1) suppresses the sulfite sensitivity but not the glucose derepression or aberrant cell morphology of a grr1 mutant of Saccharomyces cerevisiae. Genetics. 1996 Oct.144(2):511-521. Pubmedid: 8889516. Pmcid: PMC1207546.
  • Xu X, Wightman JD, Geller BL, Avram D, Bakalinsky AT. Isolation and characterization of sulfite mutants of Saccharomyces cerevisiae. Curr Genet. 1994 Jun.25(6):488-496. Pubmedid: 8082198.