Shunichi Takeda, M.D., Ph.D. Professor
The Department of Radiation Genetics was founded for the purpose of basic research and education in the field of Radiation Biology in 1961. Dr. Shunichi Takeda took over a departmental Head in 1998, and has studied molecular mechanism of radiotherapy and chemotherapy of tumors by employing a reverse genetic approach using a chicken B lymphocyte line. Our unique and efficient system allows students to publish their data in qualified journals while quickly learning essence of genetics and experimental techniques.
Research and EducationWhat is reverse genetics？
Gene targeting technologies in cells or animals, and phenotype analysis of the resulting mutants are powerful tools to learn about gene function. We have developed gene targeting systems using the chicken B lymphocyte line DT40, and have used these systems to understand the function of a variety of genes in DNA repair, recombination, and replication. A defect in these processes often leads to tumor genesis. The understanding of the molecular details of these defects is thus useful for development of anti-cancer therapy.
Learn efficiently advanced technology
Using DT40 cells, Ph.D. students can learn all basic molecular and cellular biology techniques in projects involving gene disruption and phenotype analysis. You can learn effectively from your colleagues because everybody in our laboratory shares the same experimental methods and materials while studying different genes. You can study the systems and publish data in three years to defend your thesis. Seminars are done in English twice a week. We will also support a few months externship in top laboratories in Europe or U.S during the Ph.D. course. All the recent publications were done by Ph.D. students and staff scientists of the laboratory.
Picture 1) An example of collaborative projects with National Institutes of Health (NIH, USA). Four different anti-cancer drugs but in a same category are exposed to ~50 kinds of DT40 mutant cell lines. The disrupted genes are indicated on the left. We examined cellular survival of the mutants to each drug, and compared with the survival of wild type cells. The left and right bars mean that the mutant cells are sensitive (lower survival rate than wild type) and resistant (higher survival rate than wild type), respectively. The height of bar corresponds to the significance of sensitivity or resistance. These date revealed the significantly involved genes for the repair of the drug-induced lesion. Furthermore, we found that the involved repair genes are very different by drugs even though the drugs are in the same category.
Our lab members.
- Sasanuma H, Tsuda M, Morimoto S, Saha LK, Rahman MM, Kiyooka Y, Fujiike H, Cherniack AD, Itou J, Moreu EC, Toi M, Nakada S, Tanaka H, Tsutsui K, Yamada S, Nussenzweig A, Takeda S. BRCA1 ensures genome integrity by eliminating estrogen-induced pathological Topoisomerase II-DNA complexes. Proc Natl Acad Sci U S A. (in press)
- Hoa NN, Shimizu T, Shou ZW, Wang ZQ, Deshpande RA, Paull TT, Akter S, Tsuda M, Furuta R, Tsusui K, Takeda S, Sasanuma H. (2016) Mre11 is essential for the removal of lethal Topoisomerase 2 covalent cleavage complexes. Mol Cell. 64 (3): 580-92.
- Hirota K, Tsuda M, Mohiuddin, Tsurimoto T, Cohen IS, Livneh Z, Kobayashi K, Narita T, Nishihara K, Murai J, Iwai S, Guilbaud G, Sale JE, Takeda S. (2016) In vivo evidence for translesion synthesis by the replicative DNA polymerase δ. Nucleic Acids Res. 44 (15): 7242-50.
- Hirota K, Yoshikiyo K, Guilbaud G, Tsurimoto T, Murai J, Tsuda M, Phillips L, Narita T, Nishihara K, Kobayashi K, Yamada K, Nakamura J, Pommier Y, Lehmann, A, Sale J, Takeda S. (2015) The POLD3 subunit of DNA polymerase δ can promote translesion synthesis independently of DNA polymerase ζ. Nucleic Acids Res. 43 (3): 1671-83.
- Sasanuma H, Tawaramoto MS, Lao JP, Hosaka H, Sanda E, Suzuki M, Yamashita E, Hunter N, Shinohara M, Nakagawa A, Shinohara A. (2013) A new protein complex promoting the assembly of Rad51 filaments. Nat Commun. 4: 1676.
Radiation GeneticsProfessor: Shunichi Takeda
Associate Professor: Hiroyuki Sasanuma
Assistant Professor: Akira Motegi
Assistant Professor/Cross-Appointment/Memorial Sloan Kettering Cancer Center: Shintaro Yamada
TEL ： +81-75-753-4410
FAX ： +81-75-753-4419