Nukaga, Shigenari

写真a

Affiliation

School of Medicine, Department of Internal Medicine (Pulmonary Medicine) (Shinanomachi)

Position

Instructor
Page Top ▲

Career 【 Display / hide 】

  • 2010.04
    -
    2014.03

    Department of Internal Medicine, Keio University School of Medicine

  • 2014.04
    -
    2017.03

    Division of Pulmonary Medicine, Department of Medicine, Keio University, School of Medicine

  • 2017.04
    -
    2021.03

    National Hospital Organization Tokyo Medical Center

  • 2021.04
    -
    2023.03

    Division of Genome Biology, National Cancer Center Research Institute

  • 2023.04
    -
    Present

    Division of Pulmonary Medicine, Department of Medicine, Keio University School of Medicine

Page Top ▲

Academic Background 【 Display / hide 】

  • 2004.04
    -
    2010.03

    Keio University

    Graduated

Page Top ▲

Academic Degrees 【 Display / hide 】

  • Doctor of Philosophy in Medicine (PhD in Medicine), Keio University, Dissertation, 2018.03

Page Top ▲
 

Research Areas 【 Display / hide 】

  • Life Science / Genome biology (genome/transcriptome)

  • Life Science / Tumor biology (genome/transcriptome)

  • Life Science / Respiratory medicine (lung cancer)

Page Top ▲
 

Papers 【 Display / hide 】

  • 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 2023.05

    ISSN  10614036

    　View Summary

    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 )  2023.03

    　View Summary

    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 2022.12

    ISSN  26881527

    　View Summary

    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 )  2022.12

    　View Summary

    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 2022.10

    ISSN  03850684

    　View Summary

    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.

display all >>

Page Top ▲

Reviews, Commentaries, etc. 【 Display / hide 】

Page Top ▲

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

  • Identification of Novel Therapeutic Targets Based on Comprehensive Splicing Analysis of Large-scale Lung Cancer Cohorts

    2024.01
    -
    2025.12

    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, Research grant, Principal investigator

  • Elucidation of the Function of Co-existing Genetic Abnormalities Obtained from Large-scale Cancer Genome Analysis and Development for Therapeutic Applications

    2022.04
    -
    2025.03

    文部科学省・日本学術振興会, 特別研究員奨励費, Research grant, Principal investigator

  • 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

    2018.04
    -
    2020.03

    MEXT,JSPS, Grant-in-Aid for Scientific Research, Grant-in-Aid for Early-Career Scientists , Principal investigator

  • Elucidation of pharmacokinetics of molecular targeted drugs by imaging massspectrometry

    2016.04
    -
    2018.03

    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), Research grant, Principal investigator

Page Top ▲

Awards 【 Display / hide 】

  • 2021 HOPE Project Grant Senior Research Fellow

    2021, 公益財団法人 がん研究振興財団

    Type of Award： Award from publisher, newspaper, foundation, etc.

  • The 7th Keio University Department of Respiratory Medicine Alumni Association Award

    2018.07

    Type of Award： Keio commendation etc.

  • The 58th Annual Meeting of the Japan Lung Cancer Society Young Investigator Award

    2017.10, 日本肺癌学会

    Type of Award： Award from Japanese society, conference, symposium, etc.

Page Top ▲
 

Courses Taught 【 Display / hide 】

  • Internal Medicine (Respiratory)

    2024, Undergraduate (specialized)

  • Clinical Clerkship in Respiratory Medicine

    2024

Page Top ▲