Eric E. Bouhassira, PhD

 

Professor,  Hematology and  Professor,  Cell Biology Chanin Bldg., Room 514 718 430-2188 bouhassi@aecom.yu.edu Biosketch Laboratory Web Site Complete list of publications

Research interests EPIGENETICS, HUMAN EMBRYONIC STEM CELLS AND GENE THERAPY:  Epigenetic is the study of mitotically or meiotically heritable changes in gene function not associated with changes in DNA sequence. Epigenetic regulations are mediated by changes in chromatin structure that alter access of transcription factors to their cognate binding sites and therefore expression levels of genes and transgenes. Understanding these regulations is critical for gene therapy, cancer therapy and generally to gain a greater ability to modify mammalian genomes. The main focus of my lab is to understand the molecular bases of some of these epigenetic regulations. We are particularly interested in the mechanisms of establishment and maintenance of methylation patterns and in preventing silencing of gene therapy cassettes.  In order to experimentally study these position effects, we have developed Recombinase-Mediated Cassette Exchange (RMCE), a powerful method that allows highly efficient, site-specific chromosomal integration in mammalian cells. We are in the process of adapting RMCE for use in human embryonic stem cells. This will allow us to study epigenetics and silencing directly in primary human cells. We are currently developing a system to produce normal human red blood cells with embryonic, adult and fetal characteristics by forced differentiation of human ES cells. This will allow us to generate large amount of genetically homogenous, genetically modifiable normal erythroid cells at different stages of differentiation. This system will allow us to develop silencing resistant gene therapy cassettes to cure the hemoglobinopathies, and to study the establishment and maintenance of epigenetic signals directly in untransformed human cells. We have active research projects on the role of DNA methylation, histone acetylation and methylation, linker histones, repetitive elements and transcriptional interferences in the determination of expression levels.  FOR MORE DETAILS  PLEASE VISIT Laboratory Web Site

Recent publications Feng YQ, Seibler J, Alami R, Eisen A, Fiering SN, Bouhassira EE: (1999) Site-Specific Chromosomal Integration In Mammalian cells: Highly Efficient CRE Recombinase-Mediated Cassette Exchange. J. Mol. Biol. 292 (4): 779-785. Feng YQ, Alami R, EE Bouhassira (1999): Enhancer-Dependent Transcriptional Oscillations In Mouse Erythroleukemia Cells. Mol. Cell. Biol. 19: 4907-4917. Schubeler D, Lorincz MC, Cimbora DM, Telling A, Feng YQ, Bouhassira EE, Groudine M. (2000): Genomic Targeting of Methylated DNA: The influence of Methylation On transcription, Replication, Chromatin Structure And Histone Acetylation. Mol. Cell. Biol. 20(24):9103-12. Alami R, Greally JM, Tanimoto K, Hwang S, Feng YQ, Engel JD, Fiering S, Bouhassira EE (2000) The b-Globin LCR Controls Expression Levels But Does Not Prevent Heterocellular Position Effects. Hum. Mol. Genet. 9: 631-636. GG Levy, WC Nichols, EC Lian, T Foroud, JN McClintick, BM McGee, AY Yang, DR Siemieniak, KR Stark, R Gruppo, R Sarode, SB Shurin, V Chandrasekaran, SP Stabler, H Sabio, EE Bouhassira, JD Upshaw Jr, D Ginsburg, HM Tsai (2001): Mutations in a member of the ADAMTS gene family cause thrombotic thrombocytopenic purpura. Nature 4;413(6855):488-94. R Pawliuk, KA Westerman, ME Fabry, E Payen, R Tighe, EE Bouhassira, SA Acharya, J Ellis, IM London, CJ Eaves, RK Humphries, Y Beuzard, RL Nagel, P Leboulch (2001): Correction of sickle cell disease in transgenic mouse models by gene therapy. Science 294:2368-71 Feng YQ, Lorincz M, Fiering S, Greally JM, Bouhassira EE (2001): Position Effects Are Influenced by the Orientation of a Transgene With Respect To Flanking Chromatin. Mol. Cell. Biol. 21(1): 298-309. Ezterhas, EE Bouhassira, DI Martin, S Fiering (2002): Transcriptional interference by independently regulated genes occurs in any relative arrangement of the genes and is influenced by chromosomal integration position. Mol. Cell. Biol. 22(2):469-79. Hu X., M Bulger , JN Roach, SK Eszterhas, E Olivier, EE Bouhassira, MT Groudine, S Fiering (2003): Promoters of the murine embryonic beta-like globin genes Ey and betah1 do not compete for interaction with the beta-globin locus control region. Proc Natl Acad Sci U S A. 100(3):1111-5. Alami R., Y Fan, S Pack, T Sonbuchner, A Besse, Q Lin, JM Greally, AI Skoultchi, EE Bouhassira (2003): Mammalian linker histone subtypes differentially affect gene expression in vivo. Proc Natl Acad Sci U S A. 100 (10) 5920-5925. Lin C-M, H Fu, M martonovski, EE Bouhassira, MI Aladjem (2003): Dynamic Alterations of Replication Timing in Mammalian Cells. Current Biology. 17;13(12):1019-28 Chiaramonte, W Miller, EE Bouhassira (2003): Gene Length And Proximity To Neighbors Affect Genome Wide Expression Levels. Genome Research 13: 2602-2608. Chen Q, Bouhassira EE, Besse A, Suzuka SM, Fabry ME, Nagel RL, Hirsch RE (2004): Generation of transgenic mice expressing human Hb E. Blood Cells Mol Dis. 33(3):303-7. Larijani M, Frieder D, Sonbuchner TM, Bransteitter R, Goodman MF, Bouhassira EE, Scharff MD, Martin A. (2005): Methylation protects cytidines from AID-mediated deamination. Mol Immunol. 42(5):599-604. Zhou W, Inada M, Lee TP, Benten D, Lyubsky S, Bouhassira EE, Gupta S, Tsai HM. (2005): ADAMTS13 is expressed in hepatic stellate cells. Lab Invest. (epub ahead of print) Feng YQ, Warin R, Li T, Olivier E, Besse A, Lobell A, Fu H, Lin CM, Aladjem MI, Bouhassira EE. (2005): The Human b-Globin Locus Control Region Can Silence as Well as Activate Gene Expression. Mol Cell Biol.25: (10):3864-74. Zhou W, Dong L, Ginsburg D, Bouhassira EE, Tsai HM (2005). Enzymatically active ADAMTS13 variants are not inhibited by anti-ADAMTS13 autoantibodies: a novel therapeutic strategy? J Biol Chem. 280(48):39934-41. Qiu C, Hanson E, Olivier E, Inada M, Kaufman DS, Gupta S, Bouhassira EE (2005). Differentiation of human embryonic stem cells into hematopoietic cells by coculture with human fetal liver cells recapitulates the globin switch that occurs early in development. Exp Hematol. 33(12):1450-8. Fan Y, Nikitina T, Zhao J, Fleury TJ, Bhattacharyya R, Bouhassira EE, Stein A, Woodcock CL, Skoultchi AI.(2005) Histone H1 depletion in mammals alters global chromatin structure but causes specific changes in gene regulation. Cell. 123(7):1199-212. Fu H., Lixin W., Lin CH, Singhania S, Bouhassira EE, Aladjem MI (2006) Human Replicators Can Prevent Gene Silencing. Nature Biotech. M24(5):572-6. Feng YQ, Desprat R, Fu H, Olivier E, Lin CM, Lobell A, Gowda SN, Aladjem MI, Bouhassira EE. (2006). DNA methylation supports intrinsic epigenetic memory in mammalian cells. PLoS Genet. 2006 Epub 2006 Apr 28. Olivier EN, Rybicki AC, Bouhassira EE (2006). Differentiation of Human Embryonic Stem Cells Into bipotent Mesenchymal Stem Cells. Stem Cells. 2006 Apr 27 Epub ahead of print

Eric Bouhassira: Research interests | Biosketch Faculty research at a glance Birshtein | Bouhassira | Edelmann | Fyodorov | Keogh | Kielian | Kitsis | Nathenson | Query Scharff | Schildkraut | Shafritz | Singer | Skoultchi | Stanley | Steidl |Warner | Ye   Home