Theme

5-aminolevulinic acid（5-ALA), one of the natural amino acids, exists in the mitochondria of cells and produces energy “ATP” in all living organisms. We have been developing new diagnostic and therapeutic modalities against intractable disease including malignancies using 5-ALA and will contribute the medical progress.

About Research

5-ALA is the first product in porphyrin synthetic pathway and it produces heme in mitochondria and supplies heme proteins to cells. Various heme proteins are known and play various physiological roles including  mitochondria activation, anti-inflammation, antioxidation and anti-infection. Making full use of 5-ALA, our team which has long been involved in the developing new cell and gene therapy modalities has been currently developing new diagnostic and therapeutic methods for sickle cell disease and malignancies.

Metabolic Pathway of 5-ALA
Pharmacology of 5-ALA

Publication

  1. Sagara M., Miyamoto S., Itoh S., Soda Y., Tani K. Development of new oncolytic virotherapy targeting breast cancer using Coxsackievirus B3. Anticancer Res 41(1):81-89, 2021.
  2. Murahashi M., Tsuruta T., Yamada K., Hijikata Y., Ogata H., Kishimoto J., Yoshimura S., Hikichi T., Nakanishi Y., Tani K. Clinical trial of a cancer vaccine targeting VEGF and KIF20A in advanced biliary tract cancer. Anticancer Res 41(3):1485-1496, 2021.           
  3. Hijikata Y., Yokoyama K., Yokoyama N., Matsubara Y., Shimizu E., Nakashima M., Yamaguchi M., Ota Y., Lim L A., Yamaguchi R., Ito M., Tanaka Y., Denda T., Tani K., Yotsuyanagi H., Imoto S., Miyano S., Uchimaru K., Tojo A., Successful clinical sequencing by molecular tumor board in an elderly patient with refractory Sézary syndrome. JCO Precision Oncol 4:534-560,2020.
  4. Hiramoto T., Tahara M., Liao J., Soda Y., Miura Y., Kurita R., Hamana H., Inoue K., Kohara H., Hijikata Y., Okano S., Yamaguchi Y., Oda Y., Ichiyanagi K., Toh H., Sasaki H., Kishi H., Ryo A., Muraguchi A,. Takeda M., Tani K. Non-transmissible measles virus vector with segmented RNA genome establishes different types of iPSCs from hematopoietic cells. Mol Ther 28:129-141, 2020.
  5. Tahara M., Takishima Y., Miyamoto S., Nakatsu Y., Someya K., Sato M., Tani K., Takeda M. Photocontrollable mononegaviruses. Proc Natl Acad Sci U S A. 116:11587-11589,2019
  6. Kohara H., Utsugisawa T., Sakamoto C., Hirose L., Ogawa Y., Ogura H., Sugawara A,, Aoki T., Iwasaki T., Takayosh Asai T., Doisaki S., Okuno  Y., Muramatsu H., Abe  T., Kurita  R., Miyamoto  S., Sakuma T., Shiba M., Yamamoto T., Ohga S., Yoshida K., Ogawa S., Ito E., Kojima S., Kanno H., Tani K.  KLF1 Mutation E325K induces cell-cycle arrest in erythroid cells differentiated from congenital dyserythropoietic anemia (CDA) patient-specific induced pluripotent stem cells.　Exp Hematol. 73: 25-37, 2019.
  7. Jia Y., Miyamoto S., Soda Y., Takishima Y., Sagara M., Liao J., Hirose-Yotsuya L., Hijikata Y., Miura Y., Hara K., Iwanaga A., Ota Y., Tani K. Extremely low organ toxicity and strong antitumor activity of miR-34-regulated oncolytic coxsackievirus B3.　Mol Ther Oncolytics. 12: 246-258. 2019
  8. Iwata M, Hirose L, Kohara H, Liao J, Sawada R, Akiyoshi S, Tani K, Yamanishi Y. Pathway-Based Drug Repositioning for Cancers: Computational Prediction and Experimental Validation. J Medicinal Chem 61:9583-9595, 2018.
  9. Li Y, Kobayashi K, Murayama K, Kawahara K, Shima Y, Suzuki A, Tani K, Takahashi A. FEAT enhances INSL3 expression in Leydig cells. Genes to Cells 23:952-962, 2018
  10. Shitaoka K, Hamana H, Kishi H, Hayakawa Y , Kobayashi E, Sukegawa K,Piao X, Lyu F, Nagata T , Sugiyama D, Nishikawa H, Tanemura A, Katayama I, Murahashi M, Takamatsu H, Tani K, Ozawa T , Muraguchi A. Identification of tumor-associated 1 antigen-reactive T cell receptor with tumoricidal activity by single-cell repertoire analysis of tumor-infiltrating lymphocytes. Cancer Immunol Res  6:378-388;2018.
  11. Hijikata Y, Okazaki T, Tanaka Y, Murahashi M, Yamada Y, Yamada K, Takahashi A, Inoue H, Kishimoto J, Nakanishi Y, Oda Y, Nakamura Y, Tani K.A phase I clinical trial of RNF43 peptide-related immune cell therapy combined with low-dose cyclophosphamide in patients with advanced solid tumors. <https://www.ncbi.nlm.nih.gov/pubmed/29293510> PLoS One. 2018 Jan 2;13(1):e0187878. doi: 10.1371
  12. Kulkeaw K, Inoue T, Iino T, Tani K, Akashi K, Speck N, Nakanishi Y, Sugiyama D. Twist1 regulates embryonic hematopoietic differentiation through binding to Myb and Gata2 promoter regions. Blood Adv 1:1672-1681, 2017.
  13. Nosaki,K., Hamada,K., Takishima, Y., Sagara, M., Matsumura, Y., Miyamoto, S., Hijikata,Y., Okazaki, T., Nakanishi,Y., Tani,K. A novel, polymer-coated oncolytic measles virus overcomes immune suppression and induces robust antitumor activity. Mol Ther-Oncol 2016 Nov 2;3:16022. eCollection , 2016.
  14. Murahashi M.,Hijikata Y.,Yamada K.,Tanaka,Y.,Kishimoto,J., Fujii,H., Okano,S.,　Inoue, H., Marumoto, T., Takahashi, A.,Okazaki,T., Takeda,K.,　Hirakawa,M., Morita,M.,Baba,E., Mizumoto, K., Maehara, Y. , Tanaka,M.,Akashi,K.Nakanishi,Y.,Yoshida,K.,Tsunoda,T.,Tamura,K.,Nakamura,Y., Tani,K. Phase I clinical trial of a five-peptide cancer vaccine combined with cyclophosphamide in advanced solid tumors. Clin Immunol 166-167:48-58, 2016.
  15. Narusawa M, Inoue H, Sakamoto C, Matsumura Y, Takahashi A, Inoue T, Watanabe A, Miyamoto S, Miura Y, Hijikata Y, Tanaka Y, Inoue M, Takayama K, Okazaki T, Hasegawa M, Nakanishi Y , Tani K. TLR7 ligand augments GM-CSF-initiated antitumor immunity through activation of plasmacytoid dendritic cells. Cancer Immunol Res. 2:568-580, 2014.
  16. Hiramoto,T., Ebihara, Y., Mizoguchi, Y., Nakamura, K., Yamaguchi, K., Ueno, K, Nariai, N., Mochizuki, S., Yamamoto, S., Nagasaki, M., Furukawa, Y., Tani, K., Nakauchi, H., Kobayashi, M., Tsuji, K. Wnt3a stimulates maturation of impaired neutrophils developed from severe congenital neutropenia patient-derived pluripotent stem cells. Proc Natl Acad Sci USA 110:3023-3028,2013.
Kenzaburo Tani
Project Professor
Ph.D.
Yasushi Soda
Project Associate Professor
Ph.D.