KEIO RESEARCHERS INFORMATION SYSTEM

Career 【 Display / hide 】

Career 【 Display / hide 】

• 2006.04

  -

  2007.03

  慶應義塾大学病院皮膚科

• 2011.04

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  2011.06

  慶應義塾大学総合医科学研究センター

• 2011.07

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  2013.03

  日本予防医学協会

• 2013.04

  -

  2013.06

  慶應義塾大学医学部皮膚科

• 2013.07

  -

  2014.03

  東京電力病院皮膚科

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Academic Background 【 Display / hide 】

Academic Background 【 Display / hide 】

• 1998.04

  -

  2004.03

  慶應義塾大学　, 医学部医学科

  University

• 2007.04

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  2011.03

  慶應義塾大学, 医学研究科

  Graduate School, Doctoral course

Academic Degrees 【 Display / hide 】

Academic Degrees 【 Display / hide 】

• 医学博士, 慶應義塾大学, 2012.09

Research Areas 【 Display / hide 】

Research Areas 【 Display / hide 】

• Life Science / Dermatology

Research Keywords 【 Display / hide 】

Research Keywords 【 Display / hide 】

• アトピー性皮膚炎

Research Themes 【 Display / hide 】

Research Themes 【 Display / hide 】

• 皮膚マイクロバイオーム, 

  2014.04

  -

  Present

• 皮膚バリア, 

  2007.04

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  Present

Papers 【 Display / hide 】

Papers 【 Display / hide 】

• Biomarkers and patient-related factors associated with clinical outcomes in dupilumab-treated atopic dermatitis

  Kido-Nakahara M., Onozuka D., Izuhara K., Saeki H., Nunomura S., Takenaka M., Matsumoto M., Kataoka Y., Fujimoto R., Kaneko S., Morita E., Tanaka A., Hide M., Okano T., Miyagaki T., Aoki N., Nakajima K., Ichiyama S., Tonomura K., Nakagawa Y., Tamagawa-Mineoka R., Masuda K., Takeichi T., Akiyama M., Ishiuji Y., Katsuta M., Kinoshita Y., Tateishi C., Yamamoto A., Morita A., Matsuda-Hirose H., Hatano Y., Kawasaki H., Tanese K., Ohtsuki M., Kamiya K., Kabata Y., Abe R., Mitsui H., Kawamura T., Tsuji G., Furue M., Katoh N., Nakahara T.

  Journal of Allergy and Clinical Immunology: Global 3 ( 4 )  2024.11

  　View Summary

  Background: Atopic dermatitis (AD) is a common chronic eczematous skin disease with severe pruritus. Several new therapeutic agents for AD such as dupilumab, an anti–IL-4Rα antibody, have been developed in recent years. We need to predict which agent is the best choice for each patient, but this remains difficult. Objective: Our aim was to examine clinical background factors and baseline biomarkers that could predict the achievement of improved clinical outcomes in patients with AD treated with dupilumab. Methods: A multicenter, prospective observational study was conducted on 110 patients with AD. The Eczema Area and Severity Index was used as an objective assessment, and the Patient-Oriented Eczema Measure and Numerical Rating Scale for Pruritus were used as patient-reported outcomes. In addition, some clinical background factors were evaluated. Results: The achievement of an absolute Eczema Area and Severity Index of 7 or less was negatively associated with current comorbidity of food allergy and baseline serum lactate dehydrogenase (LDH) levels. There were negative associations between achievement of a Patient-Oriented Eczema Measure score of 7 or less and duration of severe AD and between achievement of an itching Numerical Rating Scale for Pruritus score of 1 or less and current comorbidity of allergic conjunctivitis or baseline serum periostin level. Furthermore, signal detection analysis showed that a baseline serum LDH level less than 328 U/L could potentially be used as a cutoff value for predicting the efficacy of dupilumab. Conclusion: Baseline biomarkers such as LDH and periostin and clinical background factors such as current comorbidity of food allergy and a long period of severe disease may be useful indicators when choosing dupilumab for systemic treatment for AD, as they can predict the efficacy of dupilumab.

  • Access to Document (DOI)

• Pharmacological Impacts of Mucopolysacccharide Polyphosphates in the Epidermis Involves Inhibition of Amphiregulin-Mediated Signals in Keratinocytes

  Hirase R., Fujita T., Miyai T., Kawasaki H., Koseki H.

  Experimental Dermatology 33 ( 10 )  2024.10

  ISSN  09066705

  　View Summary

  The epidermis, the most superficial layer of the human skin, serves a critical barrier function, protecting the body from external pathogens and allergens. Dysregulation of epidermal differentiation contributes to barrier dysfunction and has been implicated in the pathology of various dermatological diseases, including atopic dermatitis (AD). Mucopolysaccharide polysulphate (MPS) is a moisturising agent used to treat xerosis in patients with AD. However, its mechanism of action on keratinocytes, the main constituents of the epidermis, remains unclear. In this study, we investigated the effect of MPS on keratinocytes by subjecting adult human epidermal and three-dimensional cultured keratinocytes to MPS treatment, followed by transcriptome analysis. The analysis revealed that MPS treatment enhances keratinocyte differentiation and suppresses proliferation. We focused on amphiregulin (AREG), a membrane protein that belongs to the epidermal growth factor (EGF) family and possesses a heparin-binding domain, as a significant target among the genes altered by MPS. MPS exerted an inhibitory effect directly on AREG, rather than on EGF receptors or other members of the EGF family. Furthermore, AREG leads to a reduction in epidermal barrier function, whereas MPS contributes to barrier enhancement via AREG inhibition. Collectively, these findings suggest that MPS modulates barrier function through AREG inhibition, offering insights into potential therapeutic strategies for skin barrier restoration.

  • Access to Document (DOI)

• Genomic analysis and identification of a novel superantigen, SargEY, in Staphylococcus argenteus isolated from atopic dermatitis lesions

  Aziz F., Hisatsune J., Ono H.K., Kajimura J., Yu L., Masuda K., Kitagawa H., Sato'o Y., Yahara K., Yamaoka M., Nakane A., Kawasaki H., Obata S., Fukushima-Nomura A., Ito Y., Aung M.S., Amagai M., Salasia S.I.O., Ohge H., Kusunoki Y., Sugai M.

  mSphere 9 ( 7 )  2024.07

  　View Summary

  During surveillance of Staphylococcus aureus in lesions from patients with atopic dermatitis (AD), we isolated Staphylococcusargenteus, a species registered in 2011 as a new member of the genus Staphylococcus and previously considered a lineage of S. aureus. Genome sequence comparisons between S. argenteus isolates and representative S. aureus clinical isolates from various origins revealed that the S. argenteus genome from AD patients closely resembles that of S. aureus causing skin infections. We previously reported that 17%–22% of S. aureus isolated from skin infections produce staphylococcal enterotoxin Y (SEY), which predominantly induces T-cell proliferation via the T-cell receptor (TCR) Vα pathway. Complete genome sequencing of S. argenteus isolates revealed a gene encoding a protein similar to superantigen SEY, designated as SargEY, on its chromosome. Population structure analysis of S. argenteus revealed that these isolates are ST2250 lineage, which was the only lineage positive for the SEY-like gene among S. argenteus. Recombinant SargEY demonstrated immunological cross-reactivity with anti-SEY serum. SargEY could induce proliferation of human CD4+ and CD8+ T cells, as well as production of TNF-α and IFN-γ. SargEY showed emetic activity in a marmoset monkey model. SargEY and SET (a phylogenetically close but uncharacterized SE) revealed their dependency on TCR Vα in inducing human T-cell proliferation. Additionally, TCR sequencing revealed other previously undescribed Vα repertoires induced by SEH. SargEY and SEY may play roles in exacerbating the respective toxin-producing strains in AD.

  • Access to Document (DOI)

• Best practices for multimodal clinical data management and integration: An atopic dermatitis research case

  Ohta T., Hananoe A., Fukushima-Nomura A., Ashizaki K., Sekita A., Seita J., Kawakami E., Sakurada K., Amagai M., Koseki H., Kawasaki H.

  Allergology International 73 ( 2 ) 255 - 263 2024.04

  ISSN  13238930

  　View Summary

  Background: In clinical research on multifactorial diseases such as atopic dermatitis, data-driven medical research has become more widely used as means to clarify diverse pathological conditions and to realize precision medicine. However, modern clinical data, characterized as large-scale, multimodal, and multi-center, causes difficulties in data integration and management, which limits productivity in clinical data science. Methods: We designed a generic data management flow to collect, cleanse, and integrate data to handle different types of data generated at multiple institutions by 10 types of clinical studies. We developed MeDIA (Medical Data Integration Assistant), a software to browse the data in an integrated manner and extract subsets for analysis. Results: MeDIA integrates and visualizes data and information on research participants obtained from multiple studies. It then provides a sophisticated interface that supports data management and helps data scientists retrieve the data sets they need. Furthermore, the system promotes the use of unified terms such as identifiers or sampling dates to reduce the cost of pre-processing by data analysts. We also propose best practices in clinical data management flow, which we learned from the development and implementation of MeDIA. Conclusions: The MeDIA system solves the problem of multimodal clinical data integration, from complex text data such as medical records to big data such as omics data from a large number of patients. The system and the proposed best practices can be applied not only to allergic diseases but also to other diseases to promote data-driven medical research.

  • Access to Document (DOI)

• The ability of biomarkers to assess the severity of atopic dermatitis

  Nakahara T., Onozuka D., Nunomura S., Saeki H., Takenaka M., Matsumoto M., Kataoka Y., Fujimoto R., Kaneko S., Morita E., Tanaka A., Saito R., Okano T., Miyagaki T., Aoki N., Nakajima K., Ichiyama S., Kido-Nakahara M., Tonomura K., Nakagawa Y., Tamagawa-Mineoka R., Masuda K., Takeichi T., Akiyama M., Ishiuji Y., Katsuta M., Kinoshita Y., Tateishi C., Yamamoto A., Morita A., Matsuda-Hirose H., Hatano Y., Kawasaki H., Fukushima-Nomura A., Ohtsuki M., Kamiya K., Kabata Y., Abe R., Mitsui H., Kawamura T., Tsuji G., Katoh N., Furue M., Izuhara K.

  Journal of Allergy and Clinical Immunology: Global 3 ( 1 )  2024.02

  　View Summary

  Background: To develop precision medicine for atopic dermatitis (AD), it is critical to establish relevant biomarkers. However, the characteristics of various biomarkers have not been fully understood. We previously carried out the Biomarkers to Predict Clinical Improvement of AD in Patients Treated with Dupilumab (B-PAD) study, a comprehensive nationwide study in Japan, to explore biomarkers for AD. Objective: The aim of this study is to find biomarkers associated with objective and subjective clinical findings in patients with moderate-to-severe AD based on the B-PAD study and to identify biomarkers sensitive enough to assess the severity of AD. Methods: We performed the B-PAD study as a consortium composed of 19 medical facilities in Japan, enrolling 110 patients with moderate-to-severe AD. We evaluated the Eczema Area and Severity Index (EASI) for objective assessment as well as the Patient-Oriented Eczema Measure (POEM) and a numeric rating scale for pruritus (pruritis-NRS) for subjective assessment, measuring 19 biomarkers at baseline. Results: We found that 12, 6, and 7 biomarkers showed significant and positive associations with the EASI, POEM, and pruritis-NRS, respectively. Most of the biomarkers associated with either the POEM or the pruritis-NRS were included among the biomarkers associated with EASI. Of the biomarkers examined, CCL26/eotaxin-3 and SCCA2 were the most capable of assessing severity for EASI, as shown by the 2 kinds of receiver operating characteristic analyses, respectively, whereas lactate dehydrogenase was the best for both the POEM and pruritis-NRS, again using the 2 analyses. Conclusion: We found biomarkers associated with the EASI, POEM, and pruritis-NRS, respectively, based on the B-PAD study. Moreover, we identified CCL26/eotaxin-3 and/or SCCA2 as the biomarkers having the greatest ability to assess severity in the EASI; lactate dehydrogenase did the same for the POEM and pruritis-NRS. These findings will be useful in treating patients with moderate-to-severe AD.

  • Access to Document (DOI)

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

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

• Clarification of the pathogenesis of atopic disease by using filaggrin deficient mice in dry environment

  Kawasaki, Hiroshi

  科学研究費補助金研究成果報告書 2016

• Analysis of filaggrin-null mice in dry environment to understand the pathogenic mechanism of atopic dermatitis

  Kawasaki, Hiroshi

  科学研究費補助金研究成果報告書 2013

• Development of a new model for atopic dermatitis using filaggrin mutant mice

  Kawasaki, Hiroshi

  科学研究費補助金研究成果報告書 2010

Reviews, Commentaries, etc. 【 Display / hide 】

Reviews, Commentaries, etc. 【 Display / hide 】

• Exploring patient background and biomarkers associated with the development of dupilumab-associated conjunctivitis and blepharitis

  Kido-Nakahara M., Onozuka D., Izuhara K., Saeki H., Nunomura S., Takenaka M., Matsumoto M., Kataoka Y., Fujimoto R., Kaneko S., Morita E., Tanaka A., Saito R., Okano T., Miyagaki T., Aoki N., Nakajima K., Ichiyama S., Tonomura K., Nakagawa Y., Tamagawa-Mineoka R., Masuda K., Takeichi T., Akiyama M., Ishiuji Y., Katsuta M., Kinoshita Y., Tateishi C., Yamamoto A., Morita A., Matsuda-Hirose H., Hatano Y., Kawasaki H., Fukushima-Nomura A., Ohtsuki M., Kamiya K., Kabata Y., Abe R., Mitsui H., Kawamura T., Tsuji G., Furue M., Katoh N., Nakahara T.

  Allergology International 73 ( 2 ) 332 - 334 2024.04

  ISSN  13238930

  • Access to Document (DOI)

• Exploring biomarkers to predict clinical improvement of atopic dermatitis in patients treated with dupilumab (B-PAD study)

  Nakahara T., Izuhara K., Onozuka D., Saeki H., Nunomura S., Takenaka M., Matsumoto M., Kataoka Y., Fujimoto R., Kaneko S., Morita E., Tanaka A., Hide M., Okano T., Miyagaki T., Aoki N., Nakajima K., Ichiyama S., Kido-Nakahara M., Tonomura K., Nakagawa Y., Tamagawa-Mineoka R., Masuda K., Takeichi T., Akiyama M., Ishiuji Y., Katsuta M., Kinoshita Y., Tateishi C., Yamamoto A., Morita A., Matsuda-Hirose H., Hatano Y., Kawasaki H., Tanese K., Ohtsuki M., Kamiya K., Kabata Y., Abe R., Mitsui H., Kawamura T., Tsuji G., Katoh N., Furue M.

  Clinical and Experimental Allergy 53 ( 2 ) 233 - 238 2023.02

  ISSN  09547894

  • Access to Document (DOI)

Awards 【 Display / hide 】

Awards 【 Display / hide 】

• 三四会奨励賞

  2014.06, 慶應義塾大学医学部三四会

• ガルデルマ賞

  2013.10

• 第14回ガルデルマ賞

  2013.05, 日本研究皮膚科学会

• SID/JSID Young Fellow Collegiality Awards

  2011.05, 日本研究皮膚科学会

Courses Taught 【 Display / hide 】

Courses Taught 【 Display / hide 】

• LECTURE SERIES, DERMATOLOGY

  2025

Memberships in Academic Societies 【 Display / hide 】

Memberships in Academic Societies 【 Display / hide 】

• 日本臨床免疫学会

  　

• 日本皮膚科学会

  　

• 日本研究皮膚科学会

  　

• 日本免疫学会

  　

• 日本アレルギー学会

  　

Committee Experiences 【 Display / hide 】

Committee Experiences 【 Display / hide 】

• 2015.01

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  Present

  評議員, 日本臨床免疫学会