Research
Our research encompasses all fields of otolaryngology and head-and-neck surgery. All of the faculty, staffs and residents of our department have at least 1 research theme, and strive for better research and medical care. Many of our research achievements are published in famous journals and highly acclaimed from around the world.
Also, our department encourages studying abroad to the staffs. Since 2000, over 14 of them have studied at Roswell Park Cancer Institute (Buffalo, USA), Vanderbilt University (Nashville, USA), Arkansas State University (Little Rock, USA), University Children’s Hospital Zurich (Zurich, Switzerland), Karolinska Institute (Stockholm, Sweden), and H. Lee Moffitt Cancer Center at University of South Florida (Tampa, USA).
1. Mucosal immunology in upper airway. (Analyses of the tonsillar focal disease, and vaccine formulations of white birch pollinosis and otitis media in childhood)
(Tatsuya Hayashi, Miki Takahara, Kan Kishibe, Seigo Ueda, Yuki Komabayashi, and Takumi Kumai)
(1) To understand a mechanism of tonsillar focal disease
Tonsillar focal disease is defined as clinical disorders in the distant organ from the tonsil that are caused by the tonsils without any symptoms of the tonsil itself. Palmoplantar pustulosis, IgA nephropathy, and sternocostoclavicular hyperostosis are known typical tonsillar focal diseases. Tonsillectomy is effective for them; however, the detailed mechanism is still unknown. Analyses of the tonsillar focal disease is one of our lifeworks – there are 111 presentations at conferences (16 presentations at symposiums), 17 research papers (Impact Factor: 28 points), and 4 staffs awarded Ph.D. degree by this theme: Hayabusa Nozawa, Takashi Gotoh, Tomoki Yoshizaki, and Seigo Ueda. Our tonsil study is internationally recognized, and Prof. Harabuchi organized the ‘7th International Symposium on Tonsils and Mucosal Barriers of the Upper Airways’ as a president in Asahikawa city, July 2010. There were 156 presentations, and it marked the highest number ever. It was the largest in the past symposium that over 250 people including 30 people from abroad joined. In 2011, he was conferred Hokkaido Governor Award and Hokkaido Medical Association Award on a research about "Elucidation and clinical practice for tonsil –related skin, osteoarticular and renal diseases“. The efficacy of "the tonsillectomy with steroid-pulse therapy" for the IgA nephropathy is proved by a randomized multicenter trial at the renal society in 2012, and it gets attention in the field of nephrology. We need to enlighten the research to overseas as well while accumulating the immunological evidence.
(2) Vaccine therapy and bacterial epidemiological analysis for white birch pollinosis and childhood acute otitis media
Referring to development of peptide vaccine treatment to white birch pollinosis and childhood otitis media, there are 62 presentations at conferences (including 2 presentations at symposiums), 14 research papers (IF: 32 points). Three staffs awarded Ph.D. degree by this theme: Mitsuru Yanai, Yoshiya Ishida, and Yuka Nomura. Particularly, the development of the vaccine formulation for the P6 protein of nontypable Haemophilus influenzae (NTHi) is a research theme since Prof. Harabuchi studied under Prof. Howard Faden at the Division of Infectious Diseases, Department of Pediatrics, State University of New York at Buffalo, for two years from 1991. Yusuke Abe studied at the Department of Immunology, the Roswell Park Medical Institute (RPMI) in Buffalo and studied an immune response of the P6 protein under Prof. Yasmin Thanavala in 2000-2002. This study developed into the research of the immune response for the P6 protein peptide, and Yoshiya Ishida and Yuka Nomura wrote theses for their degrees. Also, study for the peptide vaccine formulation against the white birch pollinosis is the collaborative research with the Department of Pathology. Toshihiro Nagato who was a graduate student found a peptide response to a regulatory T cell and it appeared in J. Immunology. However, none is yet clinically applied. We hope to develop the research into the clinical application, considering collaboration between academia and industry.
2. Molecular oncology and tumor immunology for the head and neck cancers.
(Miki Takahara, Kan Kishibe, Toshihiro Nagato, Yuki Komabayashi, and Takumi. Kumai)
The mechanism of the development and the metastasis of head and neck cancer including tongue cancer, pharyngeal cancer, laryngeal cancer, and maxillary sinus cancer are unknown. Molecular oncology and tumor immunology for head and neck cancers is also the one of the big themes. Regarding this theme, we’ve got good results: 125 presentations at conferences (including 1 presentations at symposiums), 39 research papers (IF: 102 points). Four staffs awarded Ph.D. degree by this theme: Takeshi Ogino, Nobuyuki Bando, Akihiro Katayama, and Hiroshi Shigyo. Takeshi Ogino studied tumor immunology at the Department of Immunology of RPMI, and researched under Prof. Soldano Ferrone about a protein expression of the human leukocyte antigen class I on head and neck squamous cell carcinomas. It is one of our major achievements that two other staffs – Nobuyuki Bando and Akihiro Katayama - also studied at the same institute for the collaborative research with Prof. Ferrone. In addition, since April 2012, Toshihiro Nagato has been conducting experiments using mouse under Prof. Esteban Celis at the Department of Immunology, H. Lee Moffitt Cancer Center & Research Institute in Tampa, FL. Takumi Kumai has been studying as a graduate student under Prof. Hiroya Kobayashi at the Department of Pathology in our university to develop the immunotherapy for EGFR and cancer antigen using the HLA class II antigens restrictive epitope. In the field of the molecular oncology, we have investigated the correlation between oncogenes and patients’ prognosis on tumor growth and metastasis. Nobuyuki Bando studied maxillary cancer and an apoptotic related molecules, Akihiro Katayama studied MMP expressions in oral cancer, and Hiroshi Shigyo researched NO in laryngeal cancer. Although many clinical departments rely on basic departments on research currently, the accomplishment that these researches were conducted at our department built the basis a high quality research can be performed at the department.
3. Molecular oncology and EBV analysis for nasal NK/T cell lymphoma.
(Miki Takahara, Kan Kishibe, Seigo Ueda, Toshihiro Nagato, Yuki Komabayashi, and Takumi Kumai)
Nasal NK/T cell lymphoma is clinically characterized by progressive necrotic lesions in the nasal cavity and a poor prognosis caused by rapid progression. Since Dr. Harabuchi had reported that NK/T cell lymphoma is related to EBV in 1990 first in the world, our department has been conducting research on the onset and the prognosis. For 15 years since he was assigned, there are 104 presentations at conferences (including 1 presentations at symposiums), 25 research papers (IF: 86 points). Five staffs awarded Ph.D. degree by this theme: Miki Takahara, Toshihiro Nagato, Hideyuki Ishii, Shigetaka Moriai, and Kazumi Yoshino. Moreover, three and five projects received Grants-in-Aid for Scientific Research and for Young Scientists respectively, from Japan Society for the Promotion of Science. We have been conducting collaborative researches with both domestic and foreign institutes actively. In Japan, we conducted the collaborative research with Dr. Katsuyuki Aozasa, a former professor at the Department of Pathology, Osaka University, and published five papers. The cell lines and culture media were given by Dr. Norio Shimizu, a professor at Medical Research Institute Tokyo Medical and Dental University. Two staffs Miki Takahara and Hideyuki Ishii studied under Prof. Eva Klein at Karolinska Institute in Stockholm, Sweden, and Seigo Ueda studied under Prof. David Nadal at Children’s Hospital of Zurich University, Switzerland. So far we have found that these lymphoma cells secrete a wide variety of cytokines and chemokines by a contribution of EBV oncogenic protein LMP1, which not only induce proliferation of the lymphoma cells in a autocrine manner but enhance chemotactic reaction of lymphocytes and monocytes around the lymphoma cells in a paracrine manner, moreover, the secreted cytokines by the lymphocytes and monocytes are associated with the lymphoma cell proliferation. We hope to develop the research into clinical applications such as a molecular targeted therapy and an immunotherapy for EBV.
4. Neurophysiological researches for upper airway and larynx.
(Akihiro Katada, Isamu Kunibe, Kenichiro Nomura)
The research on neurophysiology of an upper airway and a larynx using animal models is the major research theme of our department inherited from Dr. Tokuji Unno, a former professor. Excellent researches have been were accomplished by many staffs including Satoshi Nonaka, a former associate professor and Akihiro Katada, an assistant professor. There are 124 presentations at conferences (including 12 presentations at symposiums), 28 research papers (IF: 41 points). Four staffs awarded Ph.D. degree by this theme: Isamu Kunibe, Masaaki Adachi, Takuya Arakawa, and Kenichiro Nomura. Moreover, four, two and one projects received Grants-in-Aid for Scientific Research, Encouragement of Scientists and Young Scientists, respectively. Masaaki Adachi and Ryo Ota analyzed a central neural system of swallowing reflex under Prof. Kaoru Takakusaki at Research Center for Brain Function and Medical Engineering. Akihiro Katada, Isamu Kunibe and Kenichiro Nomura put their efforts into the development of the functional electric stimulation therapy for the laryngeal paralysis from 2003 under Prof. David Zealear at the Department of Otolaryngology, Vanderbilt University in Nashville, USA. Even after they returned to Japan, we have been continuously developing the research, and it will be clinically applied to humans shortly.
