Themis, Michael - Brunel University - Department of Life Sciences, Biomedical Sciences

研究领域

Dr Themis in head of the Gene Therapy and Genotoxicity Group at Brunel University London. His work has contributed to the field of gene therapy for the past 17 years by developing viral vectors for gene transfer and in vitro and in vivo models of genotoxicity to test vector safety. His work resulted in the first correction of the KO FIX mouse model for haemophilia B using in utero gene transfer and partial correction of this model using ex-vivo stem cell gene therapy. He has also worked with numerous mouse models of disease including model for CF, DMD and LDL. In his gene therapy research he also achieved gene transfer to all tissue of the mouse. Using LV pseudotyped with rabies, VSV-G and Mokola envelopes he has achieved highly efficient including the central nervous system and is currently using the FRDA mouse model developed by Dr Mark Pook for correction of Friedreich’s Ataxia using FXN carrying lentivirus vectors using FRDA Ataxia UK, FARA US and FARA Australasia funding. Dr Themis has also developed genotoxicity models that provide highly sensitive tests for gene therapy vector adverse effects and identify novel genes that cause cancer. Using this model Dr Themis is testing the safety of gene therapy whilst treating the FRDA mouse model. Dr Themis has developed platforms for generating high titre retrovirus, lentivirus and adenovirus and is currently developing fast throughput technologies for high titre virus production and purification with the Brunel Institute for Biotechnology. Dr Themis is currently studying the relationship between retrovirus vectors and exosomes generated from FRDA cells that contain RNAs related to gene correction and control of FXN expression, respectively. With Dr Evgeny Makarov Dr Themis has isolated highly pure batches of exosomes to characterise RNA markers of cancer and control of gene expression and to find novel markers of HCC and FRDA fibroblast pathology. Dr Themis is a member of the Breast Cancer Campaign SAB, and a founder member of the British Society for Gene Therapy

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Ghorbani, M. , Themis, M. and Payne, AM. (2016) 'Genome wide classification and characterisation of CpG sites in cancer and normal cells'. Computers in Biology and Medicine, 68 pp. 57 - 66. doi: 10.1016/j.compbiomed.2015.09.023 Download publication Condiotti, R. , Goldenberg, D. , Giladi, H. , Schnitzer-Perlman, T. , et al. (2014) 'Transduction of fetal mice with a feline lentiviral vector induces liver tumors which exhibit an E2F activation signature'. Molecular Therapy, 22 (1). pp. 59 - 68. doi: 10.1038/mt.2013.193 Download publication Nowrouzi, A. , Arens, A. , Paruzynski, A. , Schmidt, M. , et al. (2013) 'The fetal mouse is a sensitive genotoxicity model that exposes lentiviral-associated mutagenesis resulting in liver oncogenesis'. Molecular Therapy, 21 (2). pp. 324 - 337. doi: 10.1038/mt.2012.224 Download publication Themis, M. (2012) 'Monitoring for potential adverse effects of prenatal gene therapy: Genotoxicity analysis in vitro and on small animal models ex vivo and in vivo'. Methods in Molecular Biology, 891 pp. 341 - 370. doi: 10.1007/978-1-61779-873-3_16 Coutelle, C. , Waddington, SN. and Themis, M. (2012) 'Monitoring for potential adverse effects of prenatal gene therapy: Mouse models for developmental aberrations and inadvertent germ line transmission'. Methods in Molecular Biology, 891 pp. 329 - 340. doi: 10.1007/978-1-61779-873-3_15 David, AL. , Abi-Nader, KN. , Weisz, B. , Shaw, SWS. , et al. (2010) 'ULTRASONOGRAPHIC DEVELOPMENT OF THE FETAL SHEEP STOMACH AND EVALUATION OF EARLY GESTATION ULTRASOUND-GUIDED IN UTERO I NTRAGASTRIC INJECTION'. TAIWANESE JOURNAL OF OBSTETRICS & GYNECOLOGY, 49 (1). pp. 23 - 29. Kennea, NL. , Waddington, SN. , Chan, J. , O'Donoghue, K. , et al. (2009) 'Differentiation of human fetal mesenchymal stem cells into cells with an oligodendrocyte phenotype'. Cell Cycle, 8 (7). pp. 1069 - 1079. Download publication Buckley, SMK. , Waddington, SN. , Jezzard, S. , Bergau, A. , et al. (2008) 'Intra-amniotic delivery of CFTR-expressing adenovirus does not reverse cystic fibrosis phenotype in inbred CFTR-knockout mice'. Molecular Therapy, 16 (5). pp. 819 - 824. doi: 10.1038/mt.2008.26 Download publication David, A. , Weisz, B. , Ruthe, A. , Peebles, DM. , et al. (2006) 'Gene transfer to human fetal tissues in vitro'. BJOG-AN INTERNATIONAL JOURNAL OF OBSTETRICS AND GYNAECOLOGY, 113 (7). pp. 863 - 863. David, AL. , Peebles, DM. , Gregory, L. , Waddington, SN. , et al. (2006) 'Clinically applicable procedure for gene delivery to fetal gut by ultrasound-guided gastric injection: Toward prenatal prevention of early-onset intestinal diseases'. HUMAN GENE THERAPY, 17 (7). pp. 767 - 779. doi: 10.1089/hum.2006.17.767 Themis, M. , Waddington, SN. , Schmidt, M. , von Kalle, C. , et al. (2006) 'Erratum: "Oncogenesis following delivery of a nonprimate lentiviral gene therapy vector to fetal and neonatal mice" (Molecular Therapy (2005) vol. 12 (763-771) 10.1016/j.ymthe.2005.07.358)'. Molecular Therapy, 13 (4). pp. 830. doi: 10.1016/j.ymthe.2005.10.003 Themis, M. , Waddington, SN. , Schmidt, M. , von Kalle, C. , et al. (2006) 'Oncogenesis following delivery of a nonprimate lentiviral gene therapy vector to fetal and neonatal mice (vol 12, pg 763, 2005)'. Molecular Therapy, 13 (4). pp. 830 - 830. doi: 10.1016/j.ymthe.2005.07.358 Tolmachov, O. , Ma, YL. , Themis, M. , Patel, P. , et al. (2006) 'Overexpression of connexin 43 using a retroviral vector improves electrical coupling of skeletal myoblasts with cardiac myocytes in vitro'. BMC Cardiovascular Disorders, 6 pp. 25 - 25. doi: 10.1186/1471-2261-6-25 Download publication Bigger, BW. , Siapati, EK. , Mistry, A. , Waddington, SN. , et al. (2006) 'Permanent partial phenotypic correction and tolerance in a mouse model of hemophilia B by stem cell gene delivery of human factor IX.'. Gene Therapy, 13 (2). pp. 117 - 126. doi: 10.1038/sj.gt.3302638 David, AL. , Weisz, B. , Gregory, L. , Themis, M. , et al. (2006) 'Ultrasound-guided injection and occlusion of the trachea in fetal sheep'. ULTRASOUND IN OBSTETRICS & GYNECOLOGY, 28 (1). pp. 82 - 88. doi: 10.1002/uog.2815 Buckley, SM. , Waddington, SN. , Jezzard, S. , Lawrence, L. , et al. (2005) 'Factors influencing adenovirus-mediated airway transduction in fetal mice'. Molecular Therapy, 12 (3). pp. 484 - 492. doi: 10.1016/j.ymthe.2005.02.020 Waddington, SN. , Kramer, MG. , Hernandez-Alcoceba, R. , Buckley, SM. , et al. (2005) 'In utero gene therapy: Current challenges and perspectives'. Molecular Therapy, 11 (5). pp. 661 - 676. doi: 10.1016/j.ymthe.2005.01.015 Al-Allaf, F. , Tolmachov, O. , Themis, M. and Coutelle, C. (2005) 'Accurate size gauging of ExoIII/S1-generated deletions by PCR analysis of ligation mixtures'. Anal Biochem, 339 (2). pp. 348 - 350. doi: 10.1016/j.ab.2004.11.008 Siapati, EK. , Bigger, BW. , Miskin, J. , Chipchase, D. , et al. (2005) 'Comparison of HIV- and EIAV-based vectors on their efficiency in transducing murine and human hematopoietic repopulating cells'. MOLECULAR THERAPY, 12 (3). pp. 537 - 546. doi: 10.1016/j.ymthe.2005.01.022 Al-Allaf, FA. , Tolmachov, O. , Themis, M. and Coutelle, C. (2005) 'Coupled analysis of bacterial transformants and ligation mixture by duplex PCR enables detection of fatal instability of a nascent recombinant plasmid'. JOURNAL OF BIOCHEMICAL AND BIOPHYSICAL METHODS, 64 (2). pp. 142 - 146. doi: 10.1016/j.jbbm.2005.04.008