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Dr Yasu Takeuchi
1.3.11
Wohl Virion Centre, Cruciform Building
Gower Street
London
UK
WC1E  6BT
Appointment
  • Reader in Molecular Virology
  • Div of Infection & Immunity
  • Faculty of Medical Sciences
Research Summary
I studied Biochemistry at the University of Tokyo where I obtained an MSc on nucleotide physico-chemistry and a PhD on the molecular biology of small nuclear RNAs. I started his research on retroviruses upon appointment as a junior lecturer at Gunma University, Japan in 1986, and have been based in the UK since 1990, initially at the Institute of Cancer Research and then at UCL, where he is Reader in Molecular Virology.

I have worked on human viruses, HIV and HTLV and mammalian gammaretroviruses including porcine endogenous retroviruses (PERV). My research in Virology has concerned several aspects including early steps of infection and envelope-receptor interaction, evolution, oncogenesis and cell immortalisation and intrinsic antiviral immunity. The applied side of my research has been focused on the use of retroviruses as vectors for gene therapy and gene transfer and on zoonotic infections in xenotransplantation.

Vector packaging cells.
I have contributed to construction of stable packaging cell lines for MLV and HIV vectors. First I jointly with Francois-Loic Cosset developed packaging cell lines producing high-titre, complement resistant MLV vectors (patent applied and published in 1995). Complement resistance is important for in vivo use of the vector. These cell lines were deposited at ECACC and distributed internationally. Subsequently using the same expression system for MLV proteins, my lab developed suspension MLV packaging cell lines (2001). More recently as a joint project with Collins lab we developed stable HIV vector packaging lines (2003). Again these cells are deposited at ECACC and internationally circulated. We are currently working on further improvement of this system for production of clinical grade vectors with improved safety, funded by a MRC grant (PI: Mary Collins).

Safety in gene therapy
Safety problems in gene therapy concerning retroviral insertion and oncogenesis have been highlighted by recent incidents in clinical trials, where children developed leukemia after treatment for severe combined immunodeficiency with retroviral vectors (Hacein-Bey-Abina et al, Science 2003, 302: 415-419). In collaboration with Mary Collins, we have develped methods to measure retroviral insertion mutagenesis in cell culture and now are screening for safer vectors with lower mutagenic potential.

Potential risk of zoonoses in xenotransplantation.
Initially led by Robin Weiss we identified endogenous retroviruses in pigs that infect human cells as a major safety threat in xenotransplantation (1997). This seminal finding was followed by our and others' studies on PERV and called for cautious approaches to development of clinical xenotransplantation in the field. As for our PERV virology studies, we identified three subgroups of PERV with distinct receptor usage (1997-1998), an effective anti-viral drug (2001) and receptor genes for PERV-A (2003). These were followed by studies on complement sensitivity of viruses produced normal and genetically modified pig cells (2003) and PERV recombination (2004). These studies have contributed to the understanding of the nature of virological function and genome organisation of PERV and help assess the risk of potential zoonosis of PERV. Studies on structure-function of PERRV-A receptors and their physiological roles are currently ongoing.

I am currently involved in an EU FP6 consortium XENOME (Engineering of porcine genome for xenotransplantation studies in primates: step towards clinical application, www.xenome.eu), as a work package leader on safety. Projects include integration site analyses of PERV in pigs, PERV epigenetics, transgenic strategies for PERV inhibition, virus discovery by microarray (with Paul Kellam) and hepatitis E virus study (with Tim Harrison).
Teaching Summary
Co-organising Virl3001 course, responsible for the tutorials since 2007. Organising an MSc course on HIV starting in 2009.
Academic Background
1986 PhD Doctor of Philosophy – Virology University of Tokyo
1981 BSc Bachelor of Science – Biophysical Science University of Tokyo
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