The highest honor given by the Society for In Vitro Biology is the Lifetime Achievement Award. It is presented to scientists who are considered pioneers or highly influential researchers to the science and art of cell culture. They are men and women who have devoted their careers to exemplary research and/or teaching. The recipients of the Lifetime Achievement Award are selected by vote of the Board of Directors from a list of nominations recommended by the Awards Committee. The Society for In Vitro Biology honored Dr. Tetsuji Okamoto and Dr. Barbara Reed with SIVB Lifetime Achievement Awards at the 2019 In Vitro Biology Meeting in Tampa, FL. This issue highlights Dr. Tetsuji Okamoto’s career. Dr. Barbara Reed’s career will be highlighted in a future issue of the In Vitro Report.
Dr. Tetsuji Okamoto Receives the 2019 Lifetime Achievement Award
On June 9, 2019 Tetsuji Okamoto, DDS, Ph.D. received the SIVB Lifetime Achievement Award at the annual meeting in Tampa, FL for his contributions to the development and clinical application of mammalian tissue culture methodologies. As an oral surgeon and a research scientist, Dr. Okamoto made important contributions to in vitro biology, growth factor biology, cancer biology and developmental biology, which qualified him for the SIVB’s most prestigious award. Dr. Okamoto’s contributions include but are not limited to the following.
- Discovery and characterization of cholesterol auxotrophy in commonly used murine myelomas, and invention of a novel method for selecting hybridomas based on cholesterol auxotrophy.
- Discovery of a human binding protein for fibroblast growth factors that may facilitate cancer.
- Independent discovery of the growth factor VEGF and identification of receptor tyrosine kinase activity.
- Development of a novel cell therapy to treat oral cancer by lymphokine–activated killer cells using a serum-free activation medium.
- Induction of jaw cartilage and tooth from undifferentiated Xenopus ectoderm in vitro and in vivo.
- Induction of craniofacial cartilage and tooth germ from undifferentiated ectoderm in vitro and in vivo and its use for tissue engineering.
- Identification and use of point mutations in diagnosis of oral and maxillo-facial disorders.
- Clinical application of photodynamic therapy for oral cancer.
- FGF, FGFR and FGF-related protein-targeted diagnosis and treatment of skeletal disorders in the cranio-maxillofacial region.
- Development of serum-free defined medium for embryonic stem cells and induced pluripotent stem (iPS) cells.
Dr. Okamoto was educated at the Hiroshima University School of Dentistry, which is now part of the Graduate Institute of Biomedical and Health Sciences. He received his DDS degree in 1980 and his Ph.D degree in 1984 with Prof. K. Okuda in the Department of Biochemistry. After a stint as a visiting scientist with Gordon H. Sato at the W. Alton Jones Cell Science Center (1984-1987), Dr. Okamoto was appointed Associate Professor in the Dept. of Oral and Maxillofacial Surgery I at Hiroshima University School of Dentistry. In 1996 Dr. Okamoto was elected Professor and Chairman in the Dept. of Molecular Oral Medicine and Maxillofacial Surgery at Hiroshima University. At the time of his election Dr. Okamoto was the youngest Professor in any dental school in Japan, and he has held this professorship for the past 22 years. In addition Dr. Okamoto concurrently served Hiroshima University as Dean of the Graduate School of Biomedical Sciences (2007-2009) and Executive Vice President of Hiroshima University (2009-2015).
As the Professor and Chairman of Molecular Oral Medicine and Maxillofacial Surgery, Dr. Okamoto has been very successful both as a clinician overseeing a very large oral surgery department and as a basic research scientist who has made significant contributions in mammalian cell culture, growth factor biology, cancer biology, and human pluripotent stem cell biology. Dr. Okamoto’s clinical interests in reconstructive surgery of developmental cranio-facial defects and in treatment of malignant oral and head and neck cancers have informed his scientific research, which in turn has produced new approaches to diagnosing and treating diseases in his patients. Here we provide several examples of the successful application of translational research, which has marked Dr. Okamoto’s career.
- He has characterized biomarkers (growth factors, receptors, and binding proteins) in oral and salivary gland cancers (eg., Okamoto, et al., 1995a, 1995b, 1996a; Myoken, et al., 1996; Zhang, et al., 2002), and he discovered a novel mutation in the FGF receptor 3 gene that causes a defect in cranio-facial development (Zhang, et al., 2005). These findings have been used in disease diagnosis, and in the latter instance to predict which patients will need corrective surgery later in life. Another mutation discovered in the Tie2 gene that caused venous malformations was also predictive of the patient’s prognosis (Wang, et al., 2004).
- Okamoto selected a clone of the A431 human epidermoid carcinoma cell line that could survive and propagate in DMEM/F12 nutrient medium without any supplements. This A431 clone allowed him and his colleagues to investigate the protein factors elaborated by human cancer cells. With these cells he independently discovered a novel cancer cell- derived endothelial cell growth factor (VEGF) (Myoken, et al., 1991) and a unique binding protein for fibroblast growth factors (Wu, et al., 1991). An antibody to VEGF made by other researchers was approved by the FDA as an anti-cancer drug (Avastin/bevacizumab). Dr. Okamoto has shown that an analog of vitamin D3 that inhibits the expression of the binding protein (HBp17/FGFBP-1) is a potential therapeutic agent for squamous cell carcinomas (Zawani, et al., 2014; Shintani, et al., 2017).
- He created a serum-free medium that could be used to generate lymphokine (IL-2)-activated killer T cells (LAK cells), and he discovered that the addition of insulin to this medium inhibited the cytotoxic activity of the activated lymphocytes (Okamoto, et al., 1996b). Dr. Okamoto used autologous LAK cells generated in this medium to treat oral cancer patients for a number of years. He is currently investigating the mechanism by which insulin inhibits cell killing activity in T-cells as this is relevant to the efficacy of CAR-T immunotherapy of human cancers.
- He developed a serum-free feeder cell-free culture system to generate and propagate mouse and human embryonic stem cells and induced pluripotent stem cells (Furue, et al., 2005, 2008; Yamasaki, et al., 2013, 2014). He has used this culture system in conjunction with a reprogramming technique that does not genetically transform cells to derive cleidocranial disease-specific pluripotent iPS cells (Yamasaki, et al., 2016) and to generate iPS cells from human dental pulp for studies on directed cell differentiation.
- He and his clinical colleagues have used lasers in conjunction with photo-activated dyes to successfully treat squamous carcinomas of the oral cavity (Toratani, et al., 2016).
These examples emphasize how Dr. Okamoto’s clinical experience influenced his research interests, which led to new approaches to diagnosing, evaluating and treating diseases. This research has generated 8 patents and over 500 peer-reviewed publications.
As a professor and department chairman, Dr. Okamoto has trained 62 clinician scientists in the Hiroshima University Graduate School of Biomedical Sciences over the past 22 years. Many of his trainees have left academia to found private dental clinics, but many have remained academic clinicians and research scientists. Dr. Okamoto currently oversees about 40 clinician scientists including three Associate Professors and seven Assistant Professors.
Outside of Hiroshima University Dr. Okamoto has made significant contributions to academic societies such as the Japanese Tissue Culture Association, the Japanese Association of Animal Cell Technology, the Japanese Stomatological Society, the Japanese Society of Oral & Maxillofacial Surgeons, the Japanese Association of Cell Biology, as well as the Society for In Vitro Biology. Dr. Okamoto joined the SIVB in 1985. He was an Associate Editor of In Vitro Cellular and Developmental Biology – Animal from 2005 to 2011, and he has served as the Editor-in-Chief of In Vitro Animal since 2011. Dr. Okamoto received the IVACS Fellow Award in 2012.
From 2000 to 2006 Dr. Okamoto conducted a molecular epidemiological study of oral and maxillofacial disorders in residents near the former Soviet nuclear test site in Semipalatinsk, Kazakhstan. He found that chronic exposure to nuclear waste radiation was associated with increased incidences of cleft palate and tooth loss. This experience inspired Dr. Okamoto to create the graduate Phoenix Education Program when he was Vice President of Hiroshima University. The program was designed to create leaders with interdisciplinary backgrounds who could direct recovery and reconstruction activities in response to radiation disasters. The experience also led to the creation of an educational exchange program between Hiroshima University and dental schools in Kazakhstan.
J. Denry Sato, D.Phil
Lifetime Achievement Awardee
Sandra L. Schneider, DrPH, EMBA, FCT
Lifetime Achievement Awardee
Furue, M., Okamoto, T., Hayashi, Y., Okochi, H., Fujimoto, M., Myoishi, Y., Abe, T., Ohnuma, K., Sato, G. H., Asashima, M., Sato, J. D. (2005) LIF as a mitogen for pluripotent mouse ES cells in a defined serum-free medium without feeder cells. In Vitro Cell Dev Biol Anim., 41:19-28.
Furue MK, Na J, Jackson JP, Okamoto T, Jones M, Baker D, Hata R, Moore HD, Sato JD, Andrews PW (2008) Heparin promotes the growth of human embryonic stem cells in a defined serum-free medium. Proc Natl Acad Sci U S A 105:13409-13414.
Myoken, Y., Y. Kayada, T. Okamoto, M. Kan, G.H. Sato, J.D. Sato (1991) Vascular endothelial cell growth factor (VEGF) produced by A431 human epidermoid carcinoma cells and identification of VEGF membrane binding sites. Proc. Natl. Acad. Sci. USA 88:5819-5823.
Myoken, Y., Y. Myoken, T. Okamoto, M. Kan, W.L. McKeehan, J.D. Sato and K. Takada (1996) Expression of fibroblast growth factor-1 (FGF-1), FGF-2, and FGF receptor-1 in a human salivary gland adenocarcinoma cell line: Evidence of autocrine growth. Int. J.Cancer 65:650-657.
Okamoto, T., Tanaka, R., Sakamoto, A., Takada, K. (1995a) Differential Expression of fibroblast growth factor receptor (FGFR)-1-FGFR4 genes is associated with malignant progression in human salivary gland tumors. Oral Oncology 2:316-319.
Okamoto, T., Sakamoto, A., Tanaka, R., Takada, K. (1995b) Expression of vascular endothelial cell growth factor receptor in normal and tumor cells, Oral Oncology, 2:320-324.
Okamoto, T., A. Sakamoto, Y. Tanaka, K. Takada, M. Kan and J.D. Sato (1996a) Expression of fibroblast growth factor binding protein HBp17 in normal and tumor cells. In Vitro Cell. Devel. Biol. 32:69-71.
Okamoto, T., R. Tani, M. Yabumoto, A. Sakamoto, K. Takada, G.H. Sato and J.D. Sato (1996b) Effects of insulin and transferrin on lymphokine-activated killer cell generation in serum-free medium. J. Immunol. Method. 195:7-14.
Shintani T, Takatsu F, Rosli SNZ, Usui E, Hamada A, Sumi K, Hayashido Y, Toratani S, Okamoto T. (2017) Eldecalcitol (ED-71), an analog of 1α,25(OH)2D3, inhibits the growth of squamous cell carcinoma (SCC) cells in vitro and in vivo by down-regulating expression of heparin-binding protein 17/fibroblast growth factor-binding protein-1 (HBp17/FGFBP-1) and FGF-2. In Vitro Cell Dev Biol Anim. 53:810-817.
Toratani S, Tani R, Kanda T, Koizumi K, Yoshioka Y, Okamoto T. (2016) Photodynamic therapy using Photofrin and excimer dye laser treatment for superficial oral squamous cell carcinomas with long-term follow up. Photodiagnosis Photodyn Ther. 14:104-110.
Wang, H., Zhang, Y., Toratani, S., Okamoto, T. (2004) Transformation of vascular endothelial cell by a point mutation in the Tie2 gene from human haemangiomas. Oncogene 23:8700-8704.
Wu, D., Kan, M., Sato, GH., Okamoto, T., J.D. Sato (1991) Characterization and molecular cloning of a putative binding protein for heparin-binding growth factors. J. Biol. Chem. 266:16778-16785.
Yamasaki S, Nabeshima K, Sotomaru Y, Taguchi Y, Mukasa H, Furue MK, Sato JD, Okamoto T (2013) Long-term serial cultivation of mouse induced pluripotent stem cells in serum-free and feeder-free defined medium. Int J Devel Biol 57:715-724.
Yamasaki S, Taguchi Y, Shimamoto A, Mukasa H, Tahara H, Okamoto T (2014) Generation of human induced pluripotent stem (iPS) cells in serum- and feeder-free defined culture and TGF-β1 regulation of pluripotency. Plos ONE 9:1-13.
Yamasaki S, Hamada A, Akagi E, Nakatao H, Ohtaka M, Nishimura K, Nakanishi M, Okamoto T (2016) Generation of Cleidocranial dysplasia-specific induced pluripotent stem cells in integration-, feeder-, and serum-free culture, In Vitro Cell Devel Biol-Anim 52:252-264.
Zawani SNZ, Shintani T, Tratani S, Okamoto T (2014) 1α,25(OH)2D3 inhibits FGF-2 release from oral squamous cell carcinoma cells through downregulation of HBp17/FGFBP-1, In Vitro Cell. Devel. Biol.-Anim 50:802-806.
Zhang, Y., H. Wang, S. Toratani, J.D. Sato, M. Kan, W.L. McKeehan, and T. Okamoto (2002) Growth inhibition by keratinocyte growth factor receptor of human salivary adenocarcinoma cells through induction of differentiation and apoptosis. Proc. Natl. Acad. Sci. USA 98:11336-11340.
Zhang, Y., Hiraishi, Y., Wang, H., Sumi, K., Hayashido, Y., Toratani, S., Kan, M., Sato JD., Okamoto, T. (2005) Constitutive Activating Mutation of the FGFR3b in Oral Squamous Cell Carcinomas, Int J Cancer 117:166-168.