KEIO RESEARCHERS INFORMATION SYSTEM

Career 【 Display / hide 】

Career 【 Display / hide 】

• 2000.05

  -

  2002.04

  慶應義塾大学医学部, 内科学, 研修医

• 2002.05

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  2004.05

  慶應義塾大学医学部, 内科学, 専修医

• 2004.06

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  2010.01

  慶應義塾大学医学部, 内科学(呼吸器), 助手

• 2007.01

  -

  2010.01

  慶應義塾大学医学部, 微生物学・免疫学, 研究員

• 2008.07

  -

  2010.01

  佐野厚生総合病院, 内科, 医員

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Academic Background 【 Display / hide 】

Academic Background 【 Display / hide 】

• 2000.03

  Keio University, Faculty of Medicine, 医学科

  University, Graduated

Academic Degrees 【 Display / hide 】

Academic Degrees 【 Display / hide 】

• 博士, Keio University, Dissertation, 2008.06

Licenses and Qualifications 【 Display / hide 】

Licenses and Qualifications 【 Display / hide 】

• 医師免許, 2000.04

Research Areas 【 Display / hide 】

Research Areas 【 Display / hide 】

• Life Science / Respiratory medicine

• Life Science / Infectious disease medicine

Research Keywords 【 Display / hide 】

Research Keywords 【 Display / hide 】

• Mycobacteriosis

Books 【 Display / hide 】

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 】

Papers 【 Display / hide 】

• Oral β-lactam combinations are effective in vitro against Mycobacterium avium, regardless of clarithromycin susceptibility

  Yoshikawa M., Nishimura T., Misawa K., Shimamura R., Suzuki K., Kashimura S., Igarashi Y., Enoki Y., Taguchi K., Hasegawa N., Namkoong H., Matsumoto K.

  Microbiology Spectrum 13 ( 11 ) 1 - 15 2025.11

  　View Summary

  The global incidence and prevalence of pulmonary disease caused by the Mycobacterium avium complex (MAC), mainly comprising M. avium and Mycobacterium intracellulare, is increasing. However, treating MAC pulmonary disease is challenging in cases of clarithromycin (CLR)-resistant MAC or where the patients experience adverse effects or drug interactions with the few available antibiotics. Therefore, developing novel and highly effective antibiotics against MAC is crucial. Although the efficacy of dual β-lactams against Mycobacterium abscessus has been receiving attention, the efficacy of dual β-lactams against MAC remains unclear. Here, we used MAC type strains and clinical isolates to determine whether dual β-lactams were effective against MAC and which combinations synergistically inhibited bacterial growth using a broth microdilution checkerboard assay with 6 oral and 22 intravenous antibiotics. The combination effect and antibacterial activity differed between M. avium and M. intracellulare. Five combinations of oral β-lactams and 78 combinations of intravenous β-lactams showed a synergistic effect against the M. avium type strain. Among the M. avium clinical isolates, faropenem combined with cefuroxime showed the highest synergistic effect, and amoxicillin combined with tebipenem showed the lowest minimum inhibitory concentration. There was no significant difference in the combination effects between the CLR-susceptible and CLR-resistant M. avium clinical isolates in these pairs. In conclusion, regardless of CLR susceptibility, the oral β-lactam combinations were effective against M. avium. Thus, when treating MAC pulmonary disease, it is crucial to determine whether M. avium or M. intracellulare is the cause. IMPORTANCE Mycobacterium avium complex causes chronic respiratory infections, but treatment is often limited by drug resistance, intolerance, or interactions. As new therapeutic strategies are urgently needed, we focused on β-lactam antibiotics, which are widely used and well tolerated. Although dual β-lactams are effective against Mycobacterium abscessus, their utility against Mycobacterium avium complex has remained largely unexplored. Our in vitro study revealed that several β-lactam combinations are effective against Mycobacterium avium, regardless of drug resistance, indicating potential for clinical use. In contrast, Mycobacterium intracellulare showed lower susceptibility to β-lactams. Given this difference in drug susceptibility, we emphasize the clinical need to distinguish Mycobacterium avium and Mycobacterium intracellulare to optimize treatment of Mycobacterium avium complex pulmonary disease.

  • Access to Document (DOI)

• Sectm1a Depletion Promotes Neutrophil Recruitment during Pneumococcal Pneumonia

  Tanaka H., Kamata H., Ishii M., Asakura T., Namkoong H., Nakagawara K., Morita A., Kusumoto T., Azekawa S., Kaji M., Nagao G., Fukunaga N., Nishimura T., Asakura K., Hasegawa N., Fukunaga K.

  American Journal of Respiratory Cell and Molecular Biology 73 ( 1 ) 60 - 72 2025.07

  ISSN  10441549

  　View Summary

  Airway epithelial cells (AECs) play an essential role in the immune response during bacterial pneumonia. Secreted and transmembrane 1a (Sectm1a) is specifically expressed in AECs during early Streptococcus pneumoniae (SP) infection. However, its function remains largely unexplored. Here, we aimed to clarify the function of Sectm1a during serotype 3 pneumococcal pneumonia primarily using an in vivo mouse model. Our findings showed that Type I IFNs directly induced Sectm1a expression in AECs. Sectm1a depletion in an in vivo mouse model improved survival rate and enhanced the clearance of intrapulmonary bacterial burden at an early stage of SP infection. Correspondingly, Sectm1a depletion increased the count of intrapulmonary γδT cells, promoted IL-17A production by these cells, and enhanced intrapulmonary neutrophil responses against SP. Notably, IL-17A production in isolated lung γδT cells was directly suppressed by Sectm1a ex vivo. Furthermore, Sectm1a depletion altered the migration and activation markers of γδT cellsin vivo, indicating that the AEC-derived Sectm1a is associated with the phenotypes of γδT cells. These findings suggest that Type I IFNs may play an important role through AEC-derived Sectm1a in this model, and Sectm1a signaling modulates excessive neutrophil inflammation and influences bacterial clearance by directly altering γδT cell functions during pneumococcal pneumonia. In summary, this study demonstrates that the Type I IFN–Sectm1a pathway could be a potential target to modify the acute response to bacterial pneumonia.

  • Access to Document (DOI)

• Breakthrough Infection After a Primary Series of COVID-19 Vaccination Induces Stronger Humoral Immunity and Equivalent Cellular Immunity to the Spike Protein Compared with Booster Shots

  Uwamino Y., Yokoyama T., Sato Y., Tanaka S., Kamoshita Y., Shibata A., Kurafuji T., Tanabe A., Arai T., Ohno A., Namkoong H., Nishimura T., Wakui M., Murata M., Hasegawa N., Matsushita H.

  Vaccines 13 ( 7 )  2025.07

  　View Summary

  Background: The long-term immune implications of administering more than four doses of COVID-19 vaccine and the impact of breakthrough infections are not fully understood. Research Design and Methods: We conducted a follow-up cohort study on Japanese healthcare workers who received more than three doses of the BNT162b2 vaccine. We assessed both the anti-SARS-CoV-2 antibody titer and cellular immunity in 429 participants and investigated the numbers, types, and brands of COVID-19 vaccines administered, as well as the episodes of COVID-19 infections after the third dose. Results: Individuals who received three total doses of vaccines with BTI episodes demonstrated higher antibody titers than those who received four total doses of vaccines with no BTIs. The cellular immune responses between these two groups were comparable. Conclusions: These findings suggest that BTIs occurring after the primary series of COVID-19 vaccinations (first to third dose) induced humoral immunity to the spike protein that is greater than that induced by booster doses (fourth or fifth dose) and elicit cellular immunity to the spike protein comparable to that of booster doses.

  • Access to Document (DOI)

• Combined dual β-lactams and diazabicyclooctane β-lactamase inhibitor is highly effective against Mycobacterium abscessus species in vitro

  Misawa K., Nishimura T., Yoshikawa M., Shimamura R., Kashimura S., Enoki Y., Taguchi K., Matsumoto K., Hasegawa N.

  Journal of Global Antimicrobial Resistance 42   142 - 150 2025.05

  ISSN  22137165

  　View Summary

  Objective: Mycobacterium abscessus pulmonary disease is a refractory infectious disease. Developing an effective treatment is urgent as the number of patients infected with M. abscessus species (MABS) is increasing worldwide. We previously reported that nacubactam, a diazabicyclooctane (DBO) β-lactamase inhibitor, could inhibit MABS β-lactamase. Few reports have indicated that dual β-lactams are effective with a DBO β-lactamase inhibitor against MABS. The objective of this study was to determine which dual β-lactams have high antibacterial activity against MABS in the presence and absence of nacubactam. Methods: Antimicrobial susceptibility tests were conducted through a checkerboard assay of 27 β-lactams using the broth microdilution method for three subspecies-type strains and 20 clinical isolates of MABS. The number of intracellular and extracellular bacteria was measured using human macrophages infected with M. abscessus treated with effective combinations confirmed in susceptibility tests. Results: In antimicrobial susceptibility tests, 91 combinations of dual β-lactams with nacubactam exhibited synergistic effects on M. abscessus JCM13569. Among them, the combination of cefazolin, cefotiam, cefoxitin, or cefuroxime with imipenem and nacubactam exhibited highly synergistic effects, resulting in low MICs against MABS clinical isolates. Without nacubactam, the combination of imipenem and cefoxitin showed the lowest MIC. In experiments using human macrophages infected with M. abscessus, these dual β-lactam combinations reduced the number of intracellular and extracellular bacteria compared with those of single β-lactams. Conclusions: The combination of cefazolin, cefotiam, cefoxitin, or cefuroxime with imipenem and nacubactam was highly effective against MABS. Without nacubactam, the combination of cefoxitin and imipenem was effective.

  • Access to Document (DOI)

• Germline variants and mosaic chromosomal alterations affect COVID-19 vaccine immunogenicity

  Sonehara K., Uwamino Y., Saiki R., Takeshita M., Namba S., Uno S., Nakanishi T., Nishimura T., Naito T., Sato G., Kanai M., Liu A., Uchida S., Kurafuji T., Tanabe A., Arai T., Ohno A., Shibata A., Tanaka S., Wakui M., Kashimura S., Tomi C., Hara A., Yoshikawa S., Gotanda K., Misawa K., Tanaka H., Azekawa S., Wang Q.S., Edahiro R., Shirai Y., Yamamoto K., Nagao G., Suzuki T., Kiyoshi M., Ishii-Watabe A., Higashiue S., Kobayashi S., Yamaguchi H., Okazaki Y., Matsumoto N., Masumoto A., Koga H., Kanai A., Oda Y., Suzuki Y., Matsuda K., Kitagawa Y., Koike R., Kimura A., Kumanogoh A., Yoshimura A., Imoto S., Miyano S., Kanai T., Fukunaga K., Hasegawa N., Murata M., Matsushita H., Ogawa S., Okada Y., Namkoong H.

  Cell Genomics 5 ( 3 )  2025.03

  　View Summary

  Vaccine immunogenicity is influenced by the vaccinee's genetic background. Here, we perform a genome-wide association study of vaccine-induced SARS-CoV-2-specific immunoglobulin G (IgG) antibody titers and T cell immune responses in 1,559 mRNA-1273 and 537 BNT162b2 vaccinees of Japanese ancestry. SARS-CoV-2-specific antibody titers are associated with the immunoglobulin heavy chain (IGH) and major histocompatibility complex (MHC) locus, and T cell responses are associated with MHC. The lead variants at IGH contain a population-specific missense variant (rs1043109-C; p.Leu192Val) in the immunoglobulin heavy constant gamma 1 gene (IGHG1), with a strong decreasing effect (β = −0.54). Antibody-titer-associated variants modulate circulating immune regulatory proteins (e.g., LILRB4 and FCRL6). Age-related hematopoietic expanded mosaic chromosomal alterations (mCAs) affecting MHC and IGH also impair antibody production. MHC-/IGH-affecting mCAs confer infectious and immune disease risk, including sepsis and Graves’ disease. Impacts of expanded mosaic loss of chromosomes X/Y on these phenotypes were examined. Altogether, both germline and somatic mutations contribute to adaptive immunity functions.

  • Access to Document (DOI)

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

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

• Measures against COVID-19 at Keio University

  Nishimura, Tomoyasu

  学事振興資金研究成果実績報告書 (慶應義塾大学)  2022

• Elucidation of the pathophysiology of MAC pulmonary disease focusing on bacterial cell wall lipids

  Nishimura, Tomoyasu

  科学研究費補助金研究成果報告書 2021

• Investigation on pathogenesis of pulmonary diseases due to nontuberculous mycobacteria using human genomic analysis

  Nishimura, Tomoyasu

  科学研究費補助金研究成果報告書 2021

• Measures against COVID-19 at Keio University

  Nishimura, Tomoyasu

  学事振興資金研究成果実績報告書 (慶應義塾大学)  2021

• Measures against COVID-19 at Keio University

  Nishimura, Tomoyasu

  学事振興資金研究成果実績報告書 (慶應義塾大学)  2020

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Presentations 【 Display / hide 】

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

  [Domestic presentation]  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

  [Domestic presentation]  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．

  [Domestic presentation]  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．

  [Domestic presentation]  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．

  [Domestic presentation]  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 】

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

• 慶應義塾の健康関連データベースを用いた、健康問題発生における危険因子の探索

  2025.04

  -

  2026.03

  福澤基金研究補助, Research grant, Principal investigator

• 難治性肺非結核性抗酸菌症の新規薬物治療法開発

  2025.01

  -

  2026.12

  公益財団法人 シオノギ感染症研究振興財団, 創薬研究助成金, Research grant, Principal investigator

• 新規肺MABC症治療薬の開発と革新的非臨床PK/PD評価法の構築

  2024.04

  -

  2028.03

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

• 難治性肺非結核性抗酸菌症の新規薬物治療法開発

  2024.01

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  2024.12

  公益財団法人 シオノギ感染症研究振興財団, 萌芽的研究助成金, Research grant, Principal investigator

• 肺MAC症の新規治療法開発に向けた菌細胞壁脂質の解析

  2023.04

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  2026.03

  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 】

Courses Taught 【 Display / hide 】

• MEDICINE IN MODERN SOCIETY 2

  2025

• MEDICINE IN MODERN SOCIETY 1

  2025

• INFECTIOUS DISEASES

  2025

• MEDICINE IN MODERN SOCIETY 1

  2024

• INFECTIOUS DISEASES

  2024

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Courses Previously Taught 【 Display / hide 】

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

  -

  2019.03

  , 

  Full academic year, Other, Lecture, Within own ｆaculty

Social Activities 【 Display / hide 】

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

  -

  2015.02

Memberships in Academic Societies 【 Display / hide 】

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 】

Committee Experiences 【 Display / hide 】

• 2016.04

  -

  Present

  評議員, 日本感染症学会