額賀　重成 （ヌカガ　シゲナリ）

Nukaga, Shigenari

写真a

所属（所属キャンパス）

医学部 内科学教室（呼吸器） （信濃町）

職名

助教（有期）
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経歴 【 表示 ／ 非表示 】

  • 2010年04月
    -
    2014年03月

    慶應義塾大学医学部内科学教室

  • 2014年04月
    -
    2017年03月

    慶應義塾大学医学部内科学（呼吸器）

  • 2017年04月
    -
    2021年03月

    国立病院機構東京医療センター

  • 2021年04月
    -
    2023年03月

    国立がん研究センター研究所ゲノム生物学研究分野

  • 2023年04月
    -
    継続中

    慶應義塾大学医学部内科学（呼吸器）

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学歴 【 表示 ／ 非表示 】

  • 2004年04月
    -
    2010年03月

    慶應義塾大学

    卒業

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学位 【 表示 ／ 非表示 】

  • 医学博士, 慶應義塾大学, 論文, 2018年03月

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研究分野 【 表示 ／ 非表示 】

  • ライフサイエンス / ゲノム生物学 （ゲノム/トランスクリプトーム）

  • ライフサイエンス / 腫瘍生物学 （ゲノム/トランスクリプトーム）

  • ライフサイエンス / 呼吸器内科学 （肺癌）

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論文 【 表示 ／ 非表示 】

  • Single-cell analyses and host genetics highlight the role of innate immune cells in COVID-19 severity

    Edahiro R., Shirai Y., Takeshima Y., Sakakibara S., Yamaguchi Y., Murakami T., Morita T., Kato Y., Liu Y.C., Motooka D., Naito Y., Takuwa A., Sugihara F., Tanaka K., Wing J.B., Sonehara K., Tomofuji Y., Wang Q.S., Hasegawa T., Saiki R., Hyugaji T., Shimizu E., Katayama K., Kanai M., Naito T., Sasa N., Yamamoto K., Takahashi K., Harada N., Naito T., Hiki M., Matsushita Y., Takagi H., Ichikawa M., Nakamura A., Harada S., Sandhu Y., Kabata H., Masaki K., Kamata H., Ikemura S., Chubachi S., Okamori S., Terai H., Morita A., Asakura T., Sasaki J., Morisaki H., Uwamino Y., Nanki K., Uchida S., Uno S., Nishimura T., Ishiguro T., Isono T., Shibata S., Matsui Y., Hosoda C., Takano K., Nishida T., Kobayashi Y., Takaku Y., Takayanagi N., Ueda S., Tada A., Miyawaki M., Yamamoto M., Yoshida E., Hayashi R., Nagasaka T., Arai S., Kaneko Y., Sasaki K., Tagaya E., Kawana M., Arimura K., Takahashi K., Anzai T., Ito S., Endo A., Uchimura Y., Miyazaki Y., Honda T., Tateishi T., Tohda S., Ichimura N., Sonobe K., Sassa C.T., Nakajima J., Nakano Y., Nakajima Y., Anan R., Arai R., Kurihara Y., Harada Y., Nishio K., Ueda T., Azuma M., Saito R., Sado T.

    Nature Genetics （Nature Genetics）  55 （ 5 ） 753 - 767 2023年05月

    ISSN  10614036

    　概要を見る

    Mechanisms underpinning the dysfunctional immune response in severe acute respiratory syndrome coronavirus 2 infection are elusive. We analyzed single-cell transcriptomes and T and B cell receptors (BCR) of >895,000 peripheral blood mononuclear cells from 73 coronavirus disease 2019 (COVID-19) patients and 75 healthy controls of Japanese ancestry with host genetic data. COVID-19 patients showed a low fraction of nonclassical monocytes (ncMono). We report downregulated cell transitions from classical monocytes to ncMono in COVID-19 with reduced CXCL10 expression in ncMono in severe disease. Cell–cell communication analysis inferred decreased cellular interactions involving ncMono in severe COVID-19. Clonal expansions of BCR were evident in the plasmablasts of patients. Putative disease genes identified by COVID-19 genome-wide association study showed cell type-specific expressions in monocytes and dendritic cells. A COVID-19-associated risk variant at the IFNAR2 locus (rs13050728) had context-specific and monocyte-specific expression quantitative trait loci effects. Our study highlights biological and host genetic involvement of innate immune cells in COVID-19 severity.

  • Diagnostic and prognostic biomarkers for progressive fibrosing interstitial lung disease

    Watase M., Mochimaru T., Kawase H., Shinohara H., Sagawa S., Ikeda T., Yagi S., Yamamura H., Matsuyama E., Kaji M., Kurihara M., Sato M., Horiuchi K., Watanabe R., Nukaga S., Irisa K., Satomi R., Oyamada Y.

    PLoS ONE （PLoS ONE）  18 （ 3 March ）  2023年03月

    　概要を見る

    No biomarkers have been identified in bronchoalveolar lavage fluid (BALF) for predicting fibrosis progression or prognosis in progressive fibrosing interstitial lung disease (PF-ILD). We investigated BALF biomarkers for PF-ILD diagnosis and prognosis assessment. Overall, 120 patients with interstitial pneumonia who could be diagnosed with PF-ILD or non PF-ILD were enrolled in this retrospective study. PF-ILD was diagnosed according to Cottin's definition. All patients underwent bronchoscopy and BALF collection. We evaluated blood and BALF parameters, high-resolution computed tomography (HRCT) patterns, and spirometry data to identify factors influencing PF-ILD diagnosis and prognosis. On univariate logistic analysis, age, sex, the BALF white blood cell fraction (neutrophil, lymphocyte, eosinophil, and neutrophil-to-lymphocyte ratio), BALF flow cytometric analysis (CD8), and an idiopathic pulmonary fibrosis/usual interstitial pneumonia pattern on HRCT were correlated with PF-ILD diagnosis. Multivariate logistic regression analysis revealed that sex (male), age (cut-off 62 years, area under the curve [AUC] 0.67; sensitivity 0.80; specificity 0.47), white blood cell fraction in BALF (NLR, neutrophil, and lymphocyte), and CD8 in BALF (cut-off 34.2; AUC 0.66; sensitivity, 0.74; specificity, 0.62) were independent diagnostic predictors for PF-ILD. In BALF, the NLR (cut-off 8.70, AUC 0.62; sensitivity 0.62; specificity 0.70), neutrophil count (cut-off 3.0, AUC 0.59; sensitivity 0.57; specificity 0.63), and lymphocyte count (cut-off 42.0, AUC 0.63; sensitivity 0.77; specificity 0.53) were independent diagnostic predictors. In PF-ILD patients (n = 77), lactate dehydrogenase (cut-off 275, AUC 0.69; sensitivity 0.57; specificity 0.78), Krebs von den Lungen-6 (cut-off 1,140, AUC 0.74; sensitivity 0.71; specificity 0.76), baseline forced vital capacity (FVC) (cut-off 1.75 L, AUC 0.71; sensitivity, 0.93; specificity, 0.46), and BALF neutrophil ratio (cut-off 6.0, AUC 0.72; sensitivity 0.79; specificity 0.80) correlated with death within 3 years. The BALF cellular ratio, particularly the neutrophil ratio, correlated with the diagnosis and prognosis of PF-ILD. These findings may be useful in the management of patients with interstitial pneumonia.

  • Most Important Things and Associated Factors With Prioritizing Daily Life in Patients With Advanced Lung Cancer

    Kameyama N., Sato T., Arai D., Fujisawa D., Takeuchi M., Nakachi I., Kawada I., Yasuda H., Ikemura S., Terai H., Nukaga S., Nakano Y., Hirano T., Minematsu N., Asakura T., Kamatani T., Tanaka K., Suzuki S., Miyawaki M., Naoki K., Fukunaga K., Soejima K.

    JCO Oncology Practice （JCO Oncology Practice）  18 （ 12 ） E1977 - E1986 2022年12月

    ISSN  26881527

    　概要を見る

    PURPOSE:Patients' values and priorities in their lives should be appreciated from an early phase of incurable diseases such as advanced cancer. However, studies examining these characteristics have been lacking. This study attempted to determine what patients with advanced lung cancer valued most, once they had been diagnosed, and any associated factors.METHODS:Patients with newly diagnosed advanced lung cancer (N = 248) were enrolled in a questionnaire survey conducted at 16 hospitals in Japan. Their priorities were assessed using a free-text response to the question what is the most important thing to you now? at the time of diagnosis and 3 months after diagnosis. The free-text responses were classified into 10 categories for quantification. The clinical characteristics associated with the category describing daily life were further examined.RESULTS:Free-text comments were obtained from 103 (44.0%) and 66 (42.6%) patients at the time of diagnosis and at 3 months, respectively. The most frequent categories were family (at diagnosis: 50.5%; at 3 months: 50.0%) and daily life (at diagnosis: 33.0%; at 3 months: 36.4%), followed by health (at diagnosis: 32.0%; at 3 months: 27.3%) at both time points. The patients mentioning daily life, the issues related to how to spend daily life, showed significantly higher total scores and functional well-being subscale scores on the Functional Assessment of Cancer Therapy-Lung scale at both time points and lower depression scores at diagnosis and lower anxiety scores at 3 months on the Hospital Anxiety and Depression Scale.CONCLUSION:Family and daily life were highly valued by patients with advanced lung cancer at diagnosis. A better quality of life and better mood were associated with mentioning daily life, which should be taken into account in care planning to maintain patients' involvement in daily life even with incurable diseases.

  • The whole blood transcriptional regulation landscape in 465 COVID-19 infected samples from Japan COVID-19 Task Force

    Wang Q.S., Edahiro R., Namkoong H., Hasegawa T., Shirai Y., Sonehara K., Tanaka H., Lee H., Saiki R., Hyugaji T., Shimizu E., Katayama K., Kanai M., Naito T., Sasa N., Yamamoto K., Kato Y., Morita T., Takahashi K., Harada N., Naito T., Hiki M., Matsushita Y., Takagi H., Ichikawa M., Nakamura A., Harada S., Sandhu Y., Kabata H., Masaki K., Kamata H., Ikemura S., Chubachi S., Okamori S., Terai H., Morita A., Asakura T., Sasaki J., Morisaki H., Uwamino Y., Nanki K., Uchida S., Uno S., Nishimura T., Ishiguro T., Isono T., Shibata S., Matsui Y., Hosoda C., Takano K., Nishida T., Kobayashi Y., Takaku Y., Takayanagi N., Ueda S., Tada A., Miyawaki M., Yamamoto M., Yoshida E., Hayashi R., Nagasaka T., Arai S., Kaneko Y., Sasaki K., Tagaya E., Kawana M., Arimura K., Takahashi K., Anzai T., Ito S., Endo A., Uchimura Y., Miyazaki Y., Honda T., Tateishi T., Tohda S., Ichimura N., Sonobe K., Sassa C.T., Nakajima J., Nakano Y., Nakajima Y., Anan R., Arai R., Kurihara Y., Harada Y., Nishio K., Ueda T., Azuma M., Saito R., Sado T., Miyazaki Y., Sato R., Haruta Y., Nagasaki T., Yasui Y., Hasegawa Y., Mutoh Y., Kimura T., Sato T.

    Nature Communications （Nature Communications）  13 （ 1 ）  2022年12月

    　概要を見る

    Coronavirus disease 2019 (COVID-19) is a recently-emerged infectious disease that has caused millions of deaths, where comprehensive understanding of disease mechanisms is still unestablished. In particular, studies of gene expression dynamics and regulation landscape in COVID-19 infected individuals are limited. Here, we report on a thorough analysis of whole blood RNA-seq data from 465 genotyped samples from the Japan COVID-19 Task Force, including 359 severe and 106 non-severe COVID-19 cases. We discover 1169 putative causal expression quantitative trait loci (eQTLs) including 34 possible colocalizations with biobank fine-mapping results of hematopoietic traits in a Japanese population, 1549 putative causal splice QTLs (sQTLs; e.g. two independent sQTLs at TOR1AIP1), as well as biologically interpretable trans-eQTL examples (e.g., REST and STING1), all fine-mapped at single variant resolution. We perform differential gene expression analysis to elucidate 198 genes with increased expression in severe COVID-19 cases and enriched for innate immune-related functions. Finally, we evaluate the limited but non-zero effect of COVID-19 phenotype on eQTL discovery, and highlight the presence of COVID-19 severity-interaction eQTLs (ieQTLs; e.g., CLEC4C and MYBL2). Our study provides a comprehensive catalog of whole blood regulatory variants in Japanese, as well as a reference for transcriptional landscapes in response to COVID-19 infection.

  • Fusion Genes in Cancer-Toward Treatment from a Pan-Cancer Perspective

    Nukaga S., Kohno T.

    Gan to kagaku ryoho. Cancer & chemotherapy （Gan to kagaku ryoho. Cancer & chemotherapy）  49 （ 10 ） 1030 - 1034 2022年10月

    ISSN  03850684

    　概要を見る

    In recent years, genetic testing using next-generation sequencers has become widespread in the field of cancer drug therapy, and treatments based on individual genetic disorders are now routinely used. Drug development is underway to target various fusion genes among the detected genetic disorders. However, the functional significance of most of the detected fusion genes is unknown, and it is necessary to understand their biological characteristics and elucidate their functions for the development of personalized medicine. We review the molecular biology, detection, and treatment of cancer fusion genes from a pan-cancer perspective.

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総説・解説等 【 表示 ／ 非表示 】

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競争的研究費の研究課題 【 表示 ／ 非表示 】

  • 大規模肺癌コホートの網羅的スプライシング解析に基づく新規治療標的の同定

    2024年01月
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    2025年12月

    公益財団法人MSD生命科学財団, 2023年度がん領域若手研究者, 補助金,  研究代表者

  • 大規模がんゲノム解析から得られる共存する遺伝子異常の機能解明と治療応用への展開

    2022年04月
    -
    2025年03月

    文部科学省・日本学術振興会, 特別研究員奨励費, 補助金,  研究代表者

  • 第三世代EGFR－TKIの耐性化機序の解明と臨床への還元システムの構築

    2018年04月
    -
    2020年03月

    文部科学省・日本学術振興会, 科学研究費助成事業　若手研究, 額賀　重成, 若手研究, 補助金,  研究代表者

  • Imaging massspectrometryでの分子標的薬の薬物動態の解明

    2016年04月
    -
    2018年03月

    文部科学省・日本学術振興会, 科学研究費助成事業　若手研究(B), 補助金,  研究代表者

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受賞 【 表示 ／ 非表示 】

  • 令和3年度 HOPE事業助成金 シニア・リサーチフェロー

    2021年, 公益財団法人 がん研究振興財団

    受賞区分： 出版社・新聞社・財団等の賞

  • 第7回慶應義塾呼吸器内科同門会賞

    2018年07月

    受賞区分： 塾内表彰等

  • 第58回日本肺癌学会学術集会 若手奨励賞

    2017年10月, 日本肺癌学会

    受賞区分： 国内学会・会議・シンポジウム等の賞

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担当授業科目 【 表示 ／ 非表示 】

  • 内科学（呼吸器）講義

    2024年度, 学部専門科目

  • 呼吸器内科学臨床実習

    2024年度

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