Nishimura, Tomoyasu

写真a

Affiliation

Research Centers and Institutes, Health Center (Hiyoshi)

Position

Associate Professor

External Links

Career 【 Display / hide

  • 2000.05
    -
    2002.04

    慶應義塾大学医学部, 内科学, 研修医

  • 2002.05
    -
    2003.05

    川崎市立川崎病院, 内科, 医員

  • 2003.06
    -
    2004.05

    水戸赤十字病院, 内科, 医員

  • 2004.06
    -
    2010.01

    慶應義塾大学医学部, 内科学(呼吸器), 助手

  • 2007.01
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    2010.01

    慶應義塾大学医学部, 微生物学・免疫学, 研究員

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Academic Background 【 Display / hide

  • 2000.03

    Keio University, Faculty of Medicine, 医学科

    University, Graduated

Academic Degrees 【 Display / hide

  • 博士, Keio University, Dissertation, 2008.06

Licenses and Qualifications 【 Display / hide

  • 医師免許, 2000.04

 

Research Areas 【 Display / hide

  • Life Science / Respiratory medicine

  • Life Science / Infectious disease medicine

Research Keywords 【 Display / hide

  • Mycobacteriosis

 

Books 【 Display / hide

  • EBM呼吸器疾患の治療2016-2017

    Nishimura Tomoyasu, 中外医学社, 2016.01

    Scope: Interferon Gamma Release Assayの有用性は?

  • 新 呼吸器専門医テキスト

    Nishimura Tomoyasu, 南江堂, 2015.04

    Scope: 肺結核症

  • 内科研修マニュアル 改訂第2版

    Nishimura Tomoyasu, 南江堂, 2006.07

    Scope: 市中肺炎/院内肺炎

Papers 【 Display / hide

  • 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.

  • Osteoporosis in nontuberculous mycobacterial pulmonary disease: a cross-sectional study

    Tanaka H., Asakura T., Suzuki S., Okamori S., Kusumoto T., Ogawa T., Uno S., Morita A., Lee H., Namkoong H., Kamata H., Sato Y., Uwamino Y., Nishimura T., Ishii M., Fukunaga K., Hasegawa N.

    BMC Pulmonary Medicine (BMC Pulmonary Medicine)  22 ( 1 )  2022.12

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    Background: Since nontuberculous mycobacterial pulmonary disease (NTM-PD) is common in middle-aged/elderly slender women at risk of osteoporosis, we hypothesized that NTM-PD could be associated with osteoporosis. The study aimed to evaluate the prevalence of osteoporosis in patients with NTM-PD compared with that in the general population and determine the factors associated with osteoporosis in the subjects, including the serum estradiol (E2) and 25-hydroxyvitamin D (25OHD) levels. Methods: We have recruited 228 consecutive adult patients with NTM-PD from a prospective cohort study at the Keio University Hospital, who had no history of osteoporosis or osteoporosis-associated bone fracture but underwent dual-energy X-ray absorptiometry-based bone mineral density (BMD) evaluation from August 2017–September 2019. The E2 and 25OHD levels were measured in 165 patients with available stored serum samples. We performed multivariable logistic regression analyses for osteopenia and osteoporosis. Results: Osteoporosis (T-score ≤ − 2.5) and osteopenia (T-score − 1 to − 2.5) were diagnosed in 35.1% and 36.8% of patients with NTM-PD, respectively. Compared with the general population, the proportion of osteoporosis was significantly higher in 50–59-, 60–69-, and 70–79-year-old women with NTM-PD. Multivariable analysis revealed that older age (adjusted odds ratio [aOR] for 1-year increase = 1.12; 95% confidence interval [CI] = 1.07–1.18), female sex (aOR = 36.3; 95% CI = 7.57–174), lower BMI (aOR for 1 kg/m2 decrease = 1.37; 95% CI = 1.14–1.65), and chronic Pseudomonas aeruginosa (PA) infection (aOR = 6.70; 95% CI = 1.07–41.8) were independently associated with osteoporosis. Additionally, multivariable analysis in 165 patients whose serum E2 and 25OHD levels were measured showed that both low E2 levels (< 10 pg/mL) and lower 25OHD levels were independently associated with osteoporosis. Conclusions: Middle-aged/elderly women with NTM-PD have a higher prevalence of osteoporosis than the general population. BMD screening should be considered in NTM-PD, especially in older females with severe diseases such as chronic PA infection and lower BMI, and low serum E2 and 25OHD levels.

  • In vitro effects of diazabicyclooctane β-lactamase inhibitors relebactam and nacubactam against three subspecies of Mycobacterium abscessus complex

    Misawa K., Nishimura T., Kashimura S., Enoki Y., Taguchi K., Uno S., Uwamino Y., Matsumoto K., Hasegawa N.

    International Journal of Antimicrobial Agents (International Journal of Antimicrobial Agents)  60 ( 5-6 )  2022.11

    ISSN  09248579

     View Summary

    Background: Mycobacterium abscessus complex (MABC) pulmonary disease is notoriously difficult to treat due to intrinsic resistance to many common antibiotics. MABC is β-lactam-resistant as it produces class A β-lactamases, such as blaMab, which are inhibited by diazabicyclooctane (DBO) β-lactamase inhibitors. Objectives: To investigate the microbiological effects of the combination of β-lactam and DBO β-lactamase inhibitors (relebactam and nacubactam) against MABC and determine if the effects are associated with the MABC subspecies and colony morphotype. Methods: The antimicrobial susceptibility of three type strains and 20 clinical isolates of MABC to the combination of seven β-lactams with relebactam or nacubactam was evaluated using broth microdilution checkerboard assays. For these strains, expression levels of blaMab were assessed using quantitative real-time polymerase chain reaction and genotypic diversity was evaluated using 18-locus variable number tandem repeat assay. Results: Relebactam and nacubactam lowered the minimum inhibitory concentrations of β-lactams, particularly imipenem, meropenem, and tebipenem, against MABC. There was no difference in efficacy of combination treatment between three subspecies, but rough morphotypes tended to be less susceptible than smooth morphotypes. There were no differences in blaMab expression levels and genotypic diversity between the morphotypes. Conclusions: The combination of β-lactam with relebactam or nacubactam improved the efficacy of β-lactams against all MABC subspecies, but higher concentrations of β-lactams were needed for rough morphotypes.

  • DOCK2 is involved in the host genetics and biology of severe COVID-19

    Namkoong H., Edahiro R., Takano T., Nishihara H., Shirai Y., Sonehara K., Tanaka H., Azekawa S., Mikami Y., Lee H., Hasegawa T., Okudela K., Okuzaki D., Motooka D., Kanai M., Naito T., Yamamoto K., Wang Q.S., Saiki R., Ishihara R., Matsubara Y., Hamamoto J., Hayashi H., Yoshimura Y., Tachikawa N., Yanagita E., Hyugaji T., Shimizu E., Katayama K., Kato Y., Morita T., Takahashi K., Harada N., Naito T., Hiki M., Matsushita Y., Takagi H., Aoki R., Nakamura A., Harada S., Sasano H., 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.

    Nature (Nature)  609 ( 7928 ) 754 - 760 2022.09

    ISSN  00280836

     View Summary

    Identifying the host genetic factors underlying severe COVID-19 is an emerging challenge1–5. Here we conducted a genome-wide association study (GWAS) involving 2,393 cases of COVID-19 in a cohort of Japanese individuals collected during the initial waves of the pandemic, with 3,289 unaffected controls. We identified a variant on chromosome 5 at 5q35 (rs60200309-A), close to the dedicator of cytokinesis 2 gene (DOCK2), which was associated with severe COVID-19 in patients less than 65 years of age. This risk allele was prevalent in East Asian individuals but rare in Europeans, highlighting the value of genome-wide association studies in non-European populations. RNA-sequencing analysis of 473 bulk peripheral blood samples identified decreased expression of DOCK2 associated with the risk allele in these younger patients. DOCK2 expression was suppressed in patients with severe cases of COVID-19. Single-cell RNA-sequencing analysis (n = 61 individuals) identified cell-type-specific downregulation of DOCK2 and a COVID-19-specific decreasing effect of the risk allele on DOCK2 expression in non-classical monocytes. Immunohistochemistry of lung specimens from patients with severe COVID-19 pneumonia showed suppressed DOCK2 expression. Moreover, inhibition of DOCK2 function with CPYPP increased the severity of pneumonia in a Syrian hamster model of SARS-CoV-2 infection, characterized by weight loss, lung oedema, enhanced viral loads, impaired macrophage recruitment and dysregulated type I interferon responses. We conclude that DOCK2 has an important role in the host immune response to SARS-CoV-2 infection and the development of severe COVID-19, and could be further explored as a potential biomarker and/or therapeutic target.

  • The effect of the E484K mutation of SARS-CoV-2 on the neutralizing activity of antibodies from BNT162b2 vaccinated individuals

    Uwamino Y., Yokoyama T., Shimura T., Nishimura T., Sato Y., Wakui M., Kosaki K., Hasegawa N., Murata M.

    Vaccine (Vaccine)  40 ( 13 ) 1928 - 1931 2022.03

    ISSN  0264410X

     View Summary

    The reduced vaccine efficacy against the SARS-CoV-2 variant lineage B. 1.351 (beta variant) containing the E484K and N501Y mutations is well known. The E484K mutation in SARS-CoV-2 is thought to be responsible for weakened humoral immunity. Vaccine efficacy against the R.1 lineage, which contains the E484K mutation but not the N501Y mutation, is uncertain. Serum samples were collected from 100 healthy Japanese participants three weeks after receiving the second dose of the BNT162b2 vaccine, and serum neutralization antibody titers were measured against five SARS-CoV-2 variants. The geometric mean neutralization titers measured for the original and R.1 lineages were equivalent (91.90 ± 2.40 and 102.67 ± 2.28, respectively), whereas a low titer was measured for the beta variant (18.03 ± 1.92). Although further investigations with other variant strains and serum samples are essential, our results imply that the weakened humoral response is not caused solely by the E484K mutation. (UMIN000043340).

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

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Presentations 【 Display / hide

  • 外国人留学生を対象とした結核感染調査

    西村知泰,森正明,牧野伸司,広瀬寛,和井内由充子,横山裕一,武田彩乃,畔上達彦,後藤伸子,河邊博史

    第116回日本内科学会総会・講演会 (名古屋) , 

    2019.04

    Poster presentation

  • 肺MAC症の新規検査法

    Nishimura Tomoyasu

    第101回日本細菌学会関東支部総会 (東京) , 

    2018.11

    Symposium, workshop panel (nominated)

  • アスペルギルス沈降抗体陽性である肺Mycobacterium avium complex症患者の臨床的特徴

    鈴木翔二, 朝倉崇徳, 南宮湖, 岡森慧, 八木一馬, 鎌田浩史, 舩津洋平, 中野泰, 西村知泰, 石井誠, 海老原全, 別役智子, 長谷川直樹.

    第58回日本呼吸器学会学術講演会 (大阪) , 

    2018.04

    Poster presentation

  • 大学生における先天性心疾患の管理状況

    牧野伸司, 和井内由充子, 武田彩乃, 畔上達彦, 広瀬寛, 西村知泰, 横山裕一, 河邊博史, 森正明.

    第115回日本内科学会年次学術講演会 (京都) , 

    2018.04

    Poster presentation

  • 当大学医学部留学生に対するImmunization Recordの運用と考察

    武藤志保, 横山裕一, 弦巻美保, 齋藤圭美, 西村知泰, 森正明, 河邊博史.

    第55回全国大学保健管理研究集会 (宜野湾) , 

    2017.11

    Poster presentation

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

  • 医療従事者における新型コロナウイルスの感染状況調査

    2020.10
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    2021.09

    大和証券ヘルス財団, Research grant, Principal investigator

  • 慶應義塾における新型コロナウイルス感染症対策

    2020.08
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    2021.03

    慶應義塾学事振興資金, Research grant, Principal investigator

  • 肺MAC症の病態における菌細胞壁脂質の役割

    2019.06
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    2022.05

    武田科学振興財団, 医学系研究助成, Research grant, Principal investigator

  • 肺非結核性抗酸菌症患者のゲノム情報に基づいた病態解明

    2019.04
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    2022.03

    文部科学省・日本学術振興会, 科学研究費補助金, Research grant, Coinvestigator(s)

  • 菌細胞壁脂質に着目した肺MAC症の病態解明

    2019.04
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    2022.03

    文部科学省・日本学術振興会, 科学研究費補助金, Research grant, Principal investigator

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Courses Taught 【 Display / hide

  • INFECTIOUS DISEASES

    2022

  • INFECTIOUS DISEASES

    2021

  • INFECTIOUS DISEASES

    2020

  • MEDICINE IN MODERN SOCIETY 2

    2019

  • INFECTIOUS DISEASES

    2019

Courses Previously Taught 【 Display / hide

  • 感染症学

    Keio University

    2018.04
    -
    2019.03

    Full academic year, Other, Lecture, Lecturer outside of Keio

  • 現代社会と医学Ⅱ

    Keio University

    2018.04
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    2019.03

    Full academic year, Other, Lecture, Within own faculty

 

Social Activities 【 Display / hide

  • 平成27年度外務省巡回医師団

    2016.02
    -
    2016.03
  • 平成26年度外務省巡回医師団

    2015.01
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    2015.02

Memberships in Academic Societies 【 Display / hide

  • 日本免疫学会

     
  • 日本内科学会

     
  • 日本呼吸器学会

     
  • 日本呼吸器内視鏡学会

     
  • 日本感染症学会

     

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Committee Experiences 【 Display / hide

  • 2016.04
    -
    Present

    評議員, 日本感染症学会