Ozawa, Hiroyuki

写真a

Affiliation

School of Medicine, Department of Otorhinolaryngology, Head and Neck Surgery (Shinanomachi)

Position

Professor

External Links

Academic Degrees 【 Display / hide

  • 博士(医学), Keio University, 2010.01

Licenses and Qualifications 【 Display / hide

  • 耳鼻咽喉科専門医, 2003.09

  • 日本癌治療医認定医機構 癌治療認定医, 2008.04

  • 日本頭頸部外科学会 頭頸部がん専門医, 2010.10

 

Research Areas 【 Display / hide

  • Life Science / Tumor diagnostics and therapeutics

  • Life Science / Otorhinolaryngology

Research Keywords 【 Display / hide

  • Thyroid tumor

  • Skull Base Tumor

  • Head and Neck Cancer

  • Carotid Body Tumor

Research Themes 【 Display / hide

  • Genetic factor and tumor progression mechanism of carotid body tumor, 

    2014
    -
    Present

  • Head and Neck Cancer metastasis, 

    2003
    -
    Present

 

Papers 【 Display / hide

  • Development of cochlear spiral ligament fibrocytes of the common marmoset, a nonhuman model animal

    Hosoya M., Iwabu K., Kitama T., Nishiyama T., Oishi N., Okano H., Ozawa H.

    Scientific Reports (Scientific Reports)  13 ( 1 )  2023.12

     View Summary

    Spiral ligament fibrocytes generate potassium gradients, which hair cells require to convert mechanical sound waves into electrical palsy. Together with the stria vascularis, they regulate endolymph electrolyte homeostasis. Developing spiral ligament fibrocytes and generating endocochlear potential with an appropriate endolymph ion composition are essential for hearing. Understanding spiral ligament fibrocyte development is useful for studying age-related and genetic hearing loss, as well as for regenerative therapy and cochlear immunology. Despite interspecies differences, most studies of cochlear development have been conducted in rodent models due to the difficulty of using human fetal samples. This study investigated the cochlear development of spiral ligament fibrocytes in a small New World monkey species, the common marmoset (Callithrix jacchus). We examined the developmental expression of specific genes in spiral ligament fibrocytes, including those essential for the generation of endolymphatic potential. Our results showed that this animal model of spiral ligament fibrocyte development is similar to that of humans and is a suitable alternative for the analysis of human cochlear development. The time course established in this study will be useful for studying the primate-specific developmental biology of the inner ear, which may lead to novel treatment strategies for human hearing loss.

  • Correlation between genotype and phenotype with special attention to hearing in 14 Japanese cases of NF2-related schwannomatosis

    Oishi N., Noguchi M., Fujioka M., Nara K., Wasano K., Mutai H., Kawakita R., Tamura R., Karatsu K., Morimoto Y., Toda M., Ozawa H., Matsunaga T.

    Scientific Reports (Scientific Reports)  13 ( 1 )  2023.12

     View Summary

    NF2-related schwannomatosis (NF2) is an autosomal dominant genetic disorder caused by variants in the NF2 gene. Approximately 50% of NF2 patients inherit pathogenic variants, and the remainder acquire de novo variants. NF2 is characterized by development of bilateral vestibular schwannomas. The genetic background of Japanese NF2 cases has not been fully investigated, and the present report performed a genetic analysis of 14 Japanese NF2 cases and examined genotype–phenotype correlations. DNA samples collected from peripheral blood were analyzed by next-generation sequencing, multiplex ligation-dependent probe amplification analysis, and in vitro electrophoresis. Ten cases had pathogenic or likely pathogenic variants in the NF2 gene, with seven truncating variants and three non-truncating variants. The age of onset in all seven cases with truncating variants was < 20 years. The age of onset significantly differed among cases with truncating NF2 variants, non-truncating NF2 variants, and no NF2 variants. However, the clinical course of tumor growth and hearing deterioration were not predicted only by germline pathogenic NF2 variants. The rate of truncating variants was higher in the present study than that of previous reports. Genotype–phenotype correlations in the age of onset were present in the analyzed Japanese NF2 cases.

  • Apoptosis of type I spiral ganglion neuron cells in Otof-mutant mice

    Tsuzuki N., Namba K., Saegusa C., Mutai H., Nishiyama T., Oishi N., Matsunaga T., Fujioka M., Ozawa H.

    Neuroscience Letters (Neuroscience Letters)  803 2023.04

    ISSN  03043940

     View Summary

    Otof, which encodes otoferlin, knockout mice are considered model mice for auditory neuropathy spectrum disorder, which is characterized by an absent auditory brainstem response (ABR) despite preserved distortion product otoacoustic emission (DPOAE). Although otoferlin-deficient mice lack neurotransmitter release at the inner hair cell (IHC) synapse, it remains unclear how the Otof mutation affects spiral ganglions. Thus, we used Otof-mutant mice carrying the Otoftm1a(KOMP)Wtsi allele (Otoftm1a) and analyzed spiral ganglion neurons (SGNs) in Otoftm1a/tm1a mice by immunolabeling type Ⅰ SGNs (SGN-Ⅰ) and type II SGNs (SGN-II). We also examined apoptotic cells in SGNs. Four-week-old Otoftm1a/tm1a mice had an absent ABR but normal DPOAEs. The number of SGNs was significantly lower in Otoftm1a/tm1a mice on postnatal day 7 (P7), P14, and P28 compared with that of wild-type mice. Moreover, significantly more apoptotic SGNs were observed in Otoftm1a/tm1a mice than in wild-type mice on P7, P14, and P28. SGN-IIs were not significantly reduced in Otoftm1a/tm1a mice on P7, P14, and P28. No apoptotic SGN-IIs were observed under our experimental conditions. In summary, Otoftm1a/tm1a mice showed a reduction in SGNs accompanied by apoptosis of SGN-Ⅰs even before the onset of hearing. We speculate that the reduction in SGNs with apoptosis is a secondary defect caused by a lack of otoferlin in IHCs. Appropriate glutamatergic synaptic inputs may be important for the survival of SGNs.

  • Molecular basis of carotid body tumor and associated clinical features in Japan identified by genomic, immunohistochemical, and clinical analyses

    Yoshihama K., Mutai H., Sekimizu M., Ito F., Saito S., Nakamura S., Mikoshiba T., Nagai R., Takebayashi A., Miya F., Kosaki K., Ozawa H., Matsunaga T.

    Clinical Genetics (Clinical Genetics)  103 ( 4 ) 466 - 471 2023.04

    ISSN  00099163

     View Summary

    Carotid body tumor (CBT) is classified as a paraganglioma (PGL). Here, we report the genetic background, protein expression pattern, and clinical findings of 30 Japanese CBT cases. Germline pathogenic or likely pathogenic (P/LP) variants of genes encoding succinate dehydrogenase subunits (SDHs) were detected in 15 of 30 cases (50%). The SDHB variants were the most frequently detected, followed by SDHA and SDHD variants. One case with SDHAF2 variant was bilateral CBT, and other two multiple PGL cases were not detected P/LP variants. The three cases with germline variants that could be tested did not have somatic P/LP variants of the same genes. Immunohistochemical analysis showed negative SDHB signals in CBT tissues in five cases with germline P/LP variants of SDHB, SDHD, or SDHA. In addition, SDHB signals in CBT tissues were negative in four of nine cases without germline P/LP variants of SDHs. These findings suggest the involvement of unidentified molecular mechanisms affecting SDHs.

  • Generation of two induced pluripotent stem cell lines from individuals without auditory disorders

    Okura S., Ishii H., Suzuki A., Saegusa C., Fujiki K., Sugano K., Suzuki N., Saeki T., Matsuzaki S., Ozawa H., Fujioka M., Hosoya M., Okano H.

    Stem Cell Research (Stem Cell Research)  67 2023.03

    ISSN  18735061

     View Summary

    We report the establishment of two human induced pluripotent stem cell (iPSC) lines from individuals without auditory disorders. Extensive audiometry tests were performed to confirm normal hearing. The generated iPSC lines expressed pluripotency genes and showed differentiation capability into the three germ layers. The iPSC lines will be used as controls for pathological analysis and drug screening for ear disorders.

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Papers, etc., Registered in KOARA 【 Display / hide

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Research Projects of Competitive Funds, etc. 【 Display / hide

  • 頭頸部癌における低酸素応答因子の免疫応答への影響の解析とその臨床応用

    2020.04
    -
    2023.03

    MEXT,JSPS, Grant-in-Aid for Scientific Research, Grant-in-Aid for Scientific Research (C), Principal investigator

  • Development of head and neck cancer treatment targeting HIF1-alpha

    2017.04
    -
    2020.03

    MEXT,JSPS, Grant-in-Aid for Scientific Research, Grant-in-Aid for Scientific Research (C), Principal investigator

  • Analysis of HIF1-alpa expression for head and neck cancer metastasis

    2014.04
    -
    2017.03

    MEXT,JSPS, Grant-in-Aid for Scientific Research, Grant-in-Aid for Scientific Research (C), Principal investigator

     View Summary

    The aim of the present study was to investigate the molecular targets of HIF1-α relevant to metastasis, and to find out an impact of HIF1-α to HNSCC metastasis by clinicopathological assays. In immunohistochemical study, the HIF-1α expression was higher in cancer cells than in normal cells of the adjacent normal mucosa. Univariate analysis revealed that high expression of HIF-1α was significantly correlated with T-classification (P=0.012), lymph node metastasis (P=0.002) and lymphatic invasion (P=0.03). HIF-1 inhibitor downregulated the expression of HIF-1α, twist, Oct3/4 and Nanog of head and neck cancer cells.
    These results suggest that HIF-1α plays a key role for the tumor progression of HNSCC through EMT and CSC property. From the present study, HIF-1α inhibition may have the possibility to suppress tumor metastasis, thus HIF-1α is attractive target for the treatment of HNSCC.

 

Courses Taught 【 Display / hide

  • OTORHINOLARYNGOLOGY: SEMINAR

    2023

  • OTORHINOLARYNGOLOGY: PRACTICE

    2023

  • OTORHINOLARYNGOLOGY

    2023

  • LECTURE SERIES, OTORHINOLARYNGOLOGY

    2023

  • CLINICAL CLERKSHIP IN OTORHINOLARYNGOLOGY

    2023

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Courses Previously Taught 【 Display / hide

  • Skull base tumors

    Keio University

    2017.04
    -
    2018.03

  • Head and Neck cancer

    Keio University

    2017.04
    -
    2018.03

 

Memberships in Academic Societies 【 Display / hide

  • The Oto-Rhino-Laryngological Society of Japan

     
  • Japan Society for Head and Neck Cancer

     
  • Japan Society for Head and Neck Surgery

     
  • Japanese Society for Skull Base Surgery

     
  • The Society of Practical Otolaryngology

     

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