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Dr Yasuhiro Takeuchi
Reader in Molecular Virology
About
Yasuhiro Takeuchi has been based in London, UK for 23 years initially at Institute of Cancer Research and then UCL. He studied Biochemistry at University of Tokyo and obtained MSc on physicochemical study of nucleic acids and then PhD on molecular biology of small nuclear RNA. He started his research on retroviruses upon the appointment as a junior lecturer at Gunma University, Japan in 1986. Since then he has been working on human viruses, HIV and HTLV and mammalian gammaretroviruses including porcine endogenous retroviruses. His research on retrovirus biology has concerned several aspects of infection and evolution with an emphasis on envelope-receptor interaction. The applied side of the research has been focused on the use of retroviruses as vectors for gene therapy and zoonotic infection in xenotransplantation. Since September 2016 Yasu has been 30% seconded to Advanced Therapies, National Institute for Biological Standards and Control (NIBSC).
Research summary
- Early HIV studies: I contributed to HIV research in late 1980s and 1990s. A biochemical study revealed that HIV reverse transcriptase has low fidelity, potentially contributing to HIV's fast evolution and vast genetic heterogeneity (e). In molecular biology studies, I made a pair of infectious HIV molecular clones with different cell tropism caused by a single point mutation in the env gene (f). This particular mutation can result in both cell tropism change and neutralizing antibody escape (g). This tropism difference was later attributed to difference in co-receptor usage (h).
- Retroviral pseudotypes: I have developed various types of retroviral pseudotypes which encode a marker gene based on murine leukemia virus (MLV) vector but bear various types of envelope proteins, initially related gammaretroviral envelopes (i). Using these pseudotypes I have shown viruses that have certain viral envelopes and/or are produced in certain cell lines are inactivated in fresh human serum with intact complement activity (c above and j). This pseudotyping technology has been expanded to non-retroviral envelopes, e.g. SARS (j) and influenza (l), and applied for serological studies.
- Gene therapy vectorology: In a long standing collaboration with Mary Collins, we have established a series of stable vector packaging cell lines; gammaretroviral (m) and lentiviral (a, b above and n). Our unique system for continuous production of lentiviral vectors can reduce the cost of vector production. We also have a track record of insertional mutagenesis studies in the vector safety area (d above o and p). These studies concern expression/activation of proviruses, interest shared by the HIV cure field.
- Retrovirus receptors: As another area of studies using retroviral pseudotypes, I have contributed to identification and characterization of retroviral receptors, including a lentivirus (FIV, q). The work on porcine endogenous retrovirus receptors (s and t) is in the context of my studies on xenotransplantation, see below.
- Xenotransplantation: With a safety concern of pig-to-human xenotransplantation, we started to study porcine endogenous retroviruses in mid 1990s and reported their ability to infect human cells in vitro (u and v). While our initial studies made the field aware of the importance of safety studies, this series of studies around xenotransplantation have been expanded. I contributed some interpretation of pig whole genome sequence (w) and identification of anti-glycan antibodies that were induced by and are present long after exposure to live pig skin (x). Prevention of immune responses to these antigens is currently a hot topic in the xenotransplantation field.