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Ellis Lab

Brief Biography

• 2010 to present, Professor, Department of Molecular Genetics, University of Toronto
• 2008 to 2010, Scientific Co-Director, Ontario Human Induced Pluripotent Stem Cell Facility
• 2001 to 2009, Associate Professor, Department of Molecular Genetics, University of Toronto.
• 2000 to present, Senior Scientist, SickKids Research Institute, Toronto.
• 1996 to 2000, Assistant Professor, Department of Molecular & Medical Genetics, University of Toronto.
• 1994 to 2000, Scientist, SickKids Research Institute, Toronto
• 1990 to 1994, Postdoctoral Fellowship at National Institute for Medical Research, London, U.K. Supervisor: Dr. Frank Grosveld
• 1985 to 1990, PhD at Mount Sinai Hospital and Department of Medical Genetics, University of Toronto. Supervisor: Dr. Alan Bernstein.
• 1980 to 1984, B.Sc. Honours at Department of Microbiology and Immunology, McGill University.

Research Interests

• Induced Pluripotent Stem (iPS) cell reprogramming to model human disease
• Epigenetics of retrovirus and lentivirus vectors in stem cells
• Gene therapy of Rett Syndrome

Previous Research Interests

• ß-globin gene regulation, chromatin structure and DNA replication
• Gene therapy of ß-thalassemia and sickle cell anemia

Research Activities

Gene therapy involves gene transfer into stem cells but is hindered by low gene expression levels. Stem cells silence retrovirus vectors by compacting DNA into inaccessible chromatin structures.

Dr. Ellis and his colleagues are characterizing retrovirus and lentivirus silencing pathways in embryonic stem cells. Vectors that resist silencing are being enhanced with insulator elements that block silent chromatin and with modified reporter genes that escape silencing. These vectors are being used for gene therapy research and for marking iPS cells.

By generating iPS cells from patients, we intend to model human disease and apply them to regenerative medicine.

Future Research Interests

Identify the gene silencing pathway and chromatin modifications that silence retrovirus and lentivirus vector expression in embryonic stem cells and transgenic mice.

Develop retrovirus and lentivirus vectors that escape gene silencing in embryonic stem cells by incorporating Insulator elements and improved promoter/reporter gene combinations. These improved vectors will be used for marking and manipulating various adult stem cells as part of the Stem Cell Network of Excellence and will be the foundation for our gene therapy efforts.

Generate patient specific iPS cell lines to model human autism, cystic fibrosis and cardiac disease. These cells may have applications for novel drug screens and regenerative medicine.

External Funding

• International Rett Syndrome Foundation
• Canadian Institutes of Health Research
• Stem Cell Network Catalyst Grant
• Ontario Ministry of Research and Innovation

Publications

Ellis J and Bhatia M. 2011. iPSC technology: platform for drug discovery. Clin Pharmacol Ther. 89(5):639-41.

Kinoshita T, Nagamatsu G, Kosaka T, Takubo K, Hotta A, Ellis J, Suda T. 2011. Ataxia-telangiectasia mutated (ATM) deficiency decreases reprogramming efficiency and leads to genomic instability in iPS cells. Biochem Biophys Res Commun. 407(2):321-6.

Cheung A.Y.L., Horvath L, Grafodatskaya D, Pasceri P, Weksberg R, Hotta A, Carrel L, Ellis J. 2011. Isolation of MECP2-null Rett Syndrome patient hiPS cells and isogenic controls through X-chromosome inactivation. Hum Mol Genet. 20(11):2103-15.

Fussner E⁺, Djuric U⁺, Strauss M, Hotta A, Perez-Iratxeta C, Lanner F, Dilworth J, Ellis J* and Bazett-Jones DP*. 2011. Constitutive heterochromatin reorganization during somatic cell reprogramming. ⁺Equal first authors, *Equal corresponding authors. EMBO J. 30(9):1778-89.

Kattman SJ., Witty A, Gagliardi M, Dubois N, Niapour M, Hotta A, Ellis J, Keller G. Stage specific optimization of Activin/Nodal and BMP4 signaling promotes efficient cardiovascular differentiation of mouse and human pluripotent stem cell lines. Cell Stem Cell 8:228-240, 2011.

Ross PJ. and Ellis J. Modeling complex neuropsychiatric disease with induced pluripotent stem cells. F1000 Biology Reports 2:82, 2010.

Ellis J*., Baum C, Benvenisty N, Mostoslavsky G, Okano H, Stanford WL, Porteus M, Sadelain M. Benefits of utilizing gene-modified iPS cells for clinical applications. Cell Stem Cell 7:429-30, 2010. *Corresponding author.

Yantha J, Tsui H, Winer S, Song A, Wu P, Paltser G, Ellis J, Dosch HM. Unexpected acceleration of Type 1 Diabetes by transgenic expression of B7-H1 in NOD mouse Peri Islet Glia. Diabetes 59:2588-96, 2010.

Djuric U and Ellis J. Epigenetics of Induced Pluripotency: the Seven-Headed Dragon. Stem Cell Research and Therapy 1:1:3, 2010.

Hotta A, Cheung A, Farra N, Garcha K, Chang WY, Pasceri P, Stanford WL, Ellis J. EOS lentiviral vector selection system for human induced pluripotent stem cells. Nature Protocols 4:1828-44, 2009.

Belmonte JCI, Ellis J, Hochedlinger K, Yamanaka S. Induced pluripotent stem cells and reprogramming: seeing the science through the hype.  Nature Reviews Genetics 10:878-83, 2009.

Sing A., Pannell D, Karaiskakis A, Sturgeon K, Djabali M, Ellis J, Lipshitz H, Cordes S. A vertebrate Polycomb response element governs segmentation of the posterior hindbrain. Cell 138(5):885-897, 2009.

Rastegar M., Hotta A, Pasceri P, Makarem M, Cheung AYL, Elliott S, Park KJ, Adachi M, Jones FS, Clarke ID, Dirks P, Ellis J. MECP2 isoform-specific vectors with regulated expression for Rett Syndrome gene therapy. PLoS ONE 4(8): e6810, 2009.

Hotta A, Cheung AY, Farra N, Vijayaragavan K, Séguin CA, Draper JS, Pasceri P, Maksakova IA, Mager DL, Rossant J, Bhatia M, Ellis J. Isolation of human iPS cells using EOS lentiviral vectors to select for pluripotency. Nature Methods 6:370-376, 2009.

Ellis J, Bruneau BG, Keller G, Lemischka IR, Nagy A, Rossant J, Srivastava D, Zandstra PW, Stanford WL. Alternative induced pluripotent stem cell characterization criteria for in vitro applications. Cell Stem Cell 4:198-199, 2009.

Hotta A, Ellis J. Retroviral vector silencing during iPS cell induction: an epigenetic beacon that signals distinct pluripotent states. J. Cellular Biochemistry 105:940-948, 2008.

Buzina A*, Lo MY*, Moffett A*,  Hotta A, Fussner E, Bharadwaj RR, Pasceri P, Garcia-Martinez JV, Bazett-Jones DP, Ellis J. Beta-globin LCR and intron elements cooperate and direct spatial reorganization for gene therapy. *Equal first authors. PLOS Genetics 4:e1000051, 2008.

Ellis J, Hotta A, Rastegar M. Retrovirus silencing by an epigenetic TRIM. Cell 131:13-14, 2007.

Ramunas J, Montgomery HJ, Kelly L, Sukonnik T, Ellis J*, Jervis EJ*. Real time fluorescence tracking of dynamic transgene variegation in stem cells. *Equal corresponding authors. Molecular Therapy 15:810-817, 2007.

Ellis J. Silencing and variegation of gammaretrovirus and lentivirus vectors. Human Gene Therapy 16:1241-1246, 2005.

Chen J, Reifsnyder PC, Scheuplein F, Schott WH, Milievsky M, Soodeen-Karamath S, Nagy A, Dosch MH, Ellis J, Koch-Nolte F, Leiter EH. "Agouti NOD": identification of a CBA-derived Idd locus on Chromosome 7 and its use for chimera production with NOD embryonic stem cells. Mammalian Genome 16:775-783, 2005.

Lam PP, Leung YM, Sheu L, Ellis J, Tsushima RG, Osborne LR, Gaisono HY. Trangenic mouse over-expressing syntaxin-1A as a diabetes model. Diabetes 54:2744-2754, 2005.

Ellis J, Yao S. Retrovirus silencing and vector design: relevance to normal and cancer stem cells? Current Gene Therapy 5:367-373, 2005.

Buzina A, Aladjem MI, Kolman JL, Wahl GM, Ellis J. Initiation of DNA replication at the human beta-globin 3' enhancer. Nucleic Acids Research 33:4412-4424, 2005.

Dalle B, Rubin JE, Alkan O, Sukonnik T, Pasceri P, Yao S, Pawliuk R, Leboulch P, Ellis J. 2005. eGFP reporter genes silence LCRbeta-globin transgene expression via CpG dinucleotides. Molecular Therapy 11:591-599, 2005.

Yao S, Sukonnik T, Kean T, Bharadwaj RR, Pasceri P, Ellis J. Retrovirus silencing, variegation, extinction, and memory are controlled by a dynamic interplay of multiple epigenetic modifications. Molecular Therapy 10:27-36,2004.

Yao S, Osborne CS, Bharadwaj RR, Pasceri P, Sukonnik T, Pannell D, Recillas-Targa F, West AG, Ellis J. Retrovirus silencer blocking by the cHS4 insulator is CTCF independent. Nucleic Acids Research 31:5317-23, 2003.

Bharadwaj RR, Trainor CD, Pasceri P, Ellis J. LCR- regulated transgene expression levels depend on the Oct-1 site in the AT-rich region of beta-globin intron-2. Blood 101:1603-1610, 2003.

Song A, Winer S, Tsui H, Sampson A, Pasceri P, Ellis J, Elliott JF, Dosch HM. Deviation of islet autoreactivity to cryptic epitopes protects NOD mice from diabetes. Eur. J. Immunol. 33:546-555, 2003.

Ostermeier GC, Liu Z, Martins RP, Bharadwaj RR, Ellis J, Draghici S, Krawetz SA. Nuclear matrix association of the human beta-globin locus utilizing a novel approach to quantitative real-time PCR. Nucleic Acids Research 31 3257-3266, 2003.

Pawliuk R, Westerman K, Fabry ME, Payen E, Tighe R, Bouhassira EE, Acharya SA, Ellis J, London IM, Eaves CJ, Humphries RK, Beuzard Y, Nagel RL, Leboulch P. Correction of sickle cell disease in transgenic mouse models by gene therapy. Science. 294:2368-71, 2001.

Pannell D, Osborne CS, Yao S, Sukonnik T, Pasceri P, Karaiskakis A, Okano M, Li E, . Lipshitz HD, Ellis J. Retrovirus vector silencing is de novo methylase independent and marked by a repressive histone code. EMBO Journal, 19:5884-5894, 2000.

Rubin JE, Pasceri P, Wu X, Leboulch P, Ellis J. Locus Control Region activity by 5'HS3 requires a functional interaction with beta-globin gene regulatory elements: expression of novel beta/gamma-globin hybrid transgenes. Blood 95:3242-3249, 2000.

Osborne CS, Pasceri P, Singal R, Sukonnik T, Ginder G, Ellis J. Amelioration of retroviral vector silencing in locus control region beta-globin-transgenic mice and transduced F9 embryonic cells. Journal of Virology, 73: 5490-5496, 1999.

Pasceri P, Pannell D, Wu X, Ellis J. Full activity from human beta-globin locus control region transgenes requires 5'HS1, distal beta-globin promoter, and 3' beta-globin sequences. Blood, 92: 653-663, 1998.

Ellis J, Tan-Un KC, Harper A, Michalovich D, Yannoutsos N, Philipsen S, Grosveld F. A dominant chromatin-opening activity in 5' hypersensitive site 3 of the human beta-globin locus control region. EMBO Journal, 15: 562-568, 1996.

Intellectual Property

Hybrid Genes for Gene Therapy in Erythroid Cells

EOS Stem Cell Expression Cassettes