WAKI Hironori

写真a

Affiliation

Graduate School of Medicine  Doctorial Course in Medicine  Bioregulatory Medicine  Department of Metabolism and Endocrinology

Mail Address

E-mail address

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Research Interests 【 display / non-display 】

  • 代謝

  • 糖尿病

  • Transcriptional regulation

  • High throughput sequencing

  • FAIRE-seq

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Graduating School 【 display / non-display 】

  • 　
    -
    1997.03

    The University of Tokyo   Faculty of Medicine   Graduated

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Graduate School 【 display / non-display 】

  • 　
    -
    2003.03

    The University of Tokyo  Graduate School, Division of Medicine  Doctor's Course  Completed

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Campus Career 【 display / non-display 】

  • 2021.06
    -
    Now

    Akita University   Graduate School of Medicine   Doctorial Course in Medicine   Bioregulatory Medicine   Department of Metabolism and Endocrinology   Professor  

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External Career 【 display / non-display 】

  • 2019.09
    -
    2021.05

    Department of Diabetes and Metabolic Diseases, Graduate School of Medicine, The University of Tokyo   Associate Professor  

  • 2018.11
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    2019.08

    Department of Diabetes and Metabolic Diseases, Graduate School of Medicine, The University of Tokyo   Lecturer  

  • 2016.09
    -
    2018.10

    Department of Molecular Sciences on Diabetes, Graduate School of Medicine, the University of Tokyo   Project Associate Professor  

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Research Areas 【 display / non-display 】

  • Life Science / Molecular biology  / Molecular biology

  • Life Science / Nutrition science and health science

  • Life Science / Cell biology  / Cellular biology

  • Life Science / Genetics  / Genomics

  • Life Science / Metabolism and endocrinology  / Diabetes and Metabolic Diseases

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Research Achievements 【 display / non-display 】

    ◆Original paper【 display / non-display 】

  • Immune checkpoint inhibitor restores daily function in patient with microsatellite instability (MSI)-high advanced endometrial cancer and poor performance status

    Ayaka Matsui, Taichi Yoshida, Yuya Takahashi, Koji Fukuda, Kazuhiro Shimazu, Daiki Taguchi, Hanae Shinozaki, Naoaki Kodama, Shunsuke Kato, Hironori Waki, Hiroshi Nanjo, Hiroyuki Shibata

    International Cancer Conference Journal ( Springer Science and Business Media LLC )    2025.02  [Refereed]

    Research paper (journal)  

    Abstract

    The immune checkpoint system suppresses T-cell activity. Unlike cytotoxic anticancer drugs that directly kill cells, immune checkpoint inhibitors (ICIs) are generally safer by stimulating tumor immunity. However, most clinical trials require patients to have a better performance status (PS), leaving limited evidence for those with poorer PS. In practice, patients may be classified with poor PS due to tumor-induced pain and motor dysfunction, even if major organs remain functional. Real-world data on non-small cell lung cancer has shown no safety difference between patients with PS 3/4 and those with lower PS. Approximately 20–30% of endometrial cancer cases show microsatellite instability-high (MSI-high), the highest among common malignancies. A 46-year-old patient with advanced, recurrent endometrial cancer resistant to standard chemotherapy, and PS of 4 from severe pelvic pain, was diagnosed with MSI-high. Pembrolizumab was initiated and continued for 19 courses, after which lesions had disappeared or calcified, leading to drug discontinuation. Now, 4 and a half years post-treatment, she has regained independent mobility and returned to work, and her PS has improved to approximately 1. Side effects included Grade 2 or lower thyroiditis, hypothyroidism, and hypoadrenalism, manageable with hormone replacement therapy and temporary pembrolizumab suspension. This case underscores the need to test for MSI-high/mismatch repair deficiency in endometrial cancer and to consider ICI therapy in patients with poor PS but no major organ dysfunction. In such cases, ICI can rapidly improve overall condition, a phenomenon known as a Lazarus-type response, as seen in other cancers such as non-small cell lung cancer.

    DOI

  • GLP-1 receptor signaling restores aquaporin 4 subcellular polarization in reactive astrocytes and promotes amyloid β clearance in a mouse model of Alzheimer's disease.

    Kana Sasaki, Hiroki Fujita, Takehiro Sato, Shunske Kato, Yuya Takahashi, Yukio Takeshita, Takashi Kanda, Takashi Saito, Takamori C Saido, Satoko Hattori, Yasukazu Hozumi, Yuichiro Yamada, Hironori Waki

    Biochemical and biophysical research communications   741   151016 - 151016   2024.11

    Research paper (journal)  

    The physiological actions of a gut hormone, glucagon-like peptide-1 (GLP-1), in Alzheimer's disease (AD) brain remain poorly understood, although GLP-1 receptor (GLP-1R) expression in this organ has been shown in several experimental studies. Therefore, we explored whether the GLP-1R signaling promotes the clearance of amyloid β (Aβ) (1-42) which is a core pathological hallmark of AD, focusing on the water channel protein aquaporin 4 (AQP4) localized to astrocyte endfeet perivascular membranes in intact brain. First, we confirmed that Glp1r mRNA is predominantly expressed at perivascular site of astrocytes in normal mouse cerebral cortex through in situ hybridization analysis. Next, we observed that 20-week subcutaneous administration of a GLP-1R agonist (GLP-1RA) liraglutide significantly reduced Aβ (1-42) accumulation in the cerebral cortex and improved spatial working memory in an AD mouse model, AppNL-G-F/NL-G-F mice. Furthermore, our current data revealed that the 4-week liraglutide treatment relocalized subcellular AQP4 in morphologically injured reactive astrocytes of AppNL-G-F/NL-G-F mice to the cell surface perivascular site through PKA-mediated AQP4 phosphorylation. Such translocation of phosphorylated AQP4 to astrocyte cell surface following incubation with liraglutide was observed also in the present in vitro study using the cell line in which AQP4 cDNA was introduced into immortalized human astrocyte. These results suggest that enhanced intracerebral GLP-1R signaling following peripheral administration of GLP-1RA restores AQP4 subcellular polarization in reactive astrocytes and would promote Aβ excretion possibly through increasing AQP4-mediated intracerebral water flux in the brain in AD.

    DOI PubMed

  • Transcription factor PATZ1 promotes adipogenesis by controlling promoter regulatory loci of adipogenic factors.

    Sanil Patel, Khatanzul Ganbold, Chung Hwan Cho, Juwairriyyah Siddiqui, Ramazan Yildiz, Njeri Sparman, Shani Sadeh, Christy M Nguyen, Jiexin Wang, Julian P Whitelegge, Susan K Fried, Hironori Waki, Claudio J Villanueva, Marcus M Seldin, Shinya Sakaguchi, Wilfried Ellmeier, Peter Tontonoz, Prashant Rajbhandari

    Nature communications   15 ( 1 ) 8533 - 8533   2024.10  [Refereed]

    Research paper (journal)  

    White adipose tissue (WAT) is essential for lipid storage and systemic energy homeostasis. Understanding adipocyte formation and stability is key to developing therapies for obesity and metabolic disorders. Through a high-throughput cDNA screen, we identified PATZ1, a POZ/BTB and AT-Hook Containing Zinc Finger 1 protein, as an important adipogenic transcription factor. PATZ1 is expressed in human and mouse adipocyte precursor cells (APCs) and adipocytes. In cellular models, PATZ1 promotes adipogenesis via protein-protein interactions and DNA binding. PATZ1 ablation in mouse adipocytes and APCs leads to a reduced APC pool, decreased fat mass, and hypertrophied adipocytes. ChIP-Seq and RNA-seq analyses show that PATZ1 supports adipogenesis by interacting with transcriptional machinery at the promoter regions of key early adipogenic factors. Mass-spec results show that PATZ1 associates with GTF2I, with GTF2I modulating PATZ1's function during differentiation. These findings underscore PATZ1's regulatory role in adipocyte differentiation and adiposity, offering insights into adipose tissue development.

    DOI PubMed

  • A Comprehensive Survey on Treatment, Care, and Lifestyle Experiences among Japanese Individuals With Diabetes

    Noriko Ihana-Sugiyama, Akiko Wakui-Kimura, Takehiro Sugiyama, Kenjiro Imai, Tomoko Hosono, Hiroko Hotta, Kouko Yamamoto, Masakazu Aihara, Tomohisa Aoyama, Takayoshi Sasako, Hironori Waki, Mitsuru Ohsugi, Kohjiro Ueki, Toshimasa Yamauchi

    J. Japan Diab. Soc.   67 ( 11 ) 476 - 488   2024.09  [Refereed]

    Research paper (journal)  

  • Recurrent nocturnal hypoglycemic hemiplegia: a case report and review of the literature.

    Hanako Toyama, Kazuyuki Takahashi, Tatsunori Shimizu, Izumi Otaka, Sakiko Abe, Shunsuke Kato, Sayaka Ando, Takehiro Sato, Tsukasa Morii, Hiroki Fujita, Hironori Waki

    Endocrine journal ( Japan Endocrine Society )  71 ( 4 ) 409 - 416   2024.02  [Refereed]

    Research paper (journal)  

    A 67-year-old man with type 1 diabetes, Cronkhite-Canada syndrome, and membranous nephropathy who received insulin therapy was admitted to our hospital with right hemiplegia and dysarthria. Brain magnetic resonance imaging revealed a lesion with a high diffusion-weighted imaging signal and low apparent diffusion coefficient signal in the posterior limb of the left internal capsule. He was hypoglycemic with a blood glucose level of 56 mg/dL (3.1 mmol/L). Following glucose administration, the patient's symptoms resolved within several hours. The patient experienced similar transient hypoglycemic hemiplegia at midnight, three times within 10 days. In a literature review of 170 cases of hypoglycemic hemiplegia, 26 cases of recurrent hemiplegia were investigated. Recurrent hypoglycemic hemiplegia occurs more frequently on the right side than on the left side, and most recurrences occur within approximately a week, almost exclusively at midnight and in the early morning. We speculate that hypoglycemia-associated autonomic failure may be involved in the nocturnal recurrence of episodes. In our patient, depleted endogenous insulin secretion and lipodystrophy at the injection site, may have acted as additional factors, leading to severe hypoglycemia despite the absence of apparent autonomic neuropathy. Clinically, it is important to recognize hypoglycemia as a cause of hemiplegia to avoid unnecessary intervention and to maintain an appropriate blood glucose level at midnight and early in the morning to prevent recurrent hypoglycemic hemiplegia.

    DOI PubMed

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    ◆Introduction and explanation【 display / non-display 】

  • The Latest Science of Fat Cells

    Hironori Waki

    Medical View Point ( Iji Publishing Co., Ltd. )  44 ( 9 ) 6 - 6   2023.09

    Introduction and explanation (commerce magazine)  

  • One point advice---How much is your best weight?

    Hironori Waki

    Medical Practice   40 ( 5 ) 800 - 800   2023.05

    Introduction and explanation (scientific journal)  

  • Team approach of bariatric and metabolic surgeries (topics editor)

    Hironori Waki, Kunihisa Kobayashi

    DM Ensemble ( Nikkei Medical )  11 ( 2 ) 6 - 6   2022.08

    Introduction and explanation (scientific journal)  

  • Genetics in obesity and obeesity stigma

    Hironori Waki

    DM Ensemble ( Nikkei Medical )  11 ( 2 ) 36 - 37   2022.08

    Introduction and explanation (scientific journal)  

  • Brown and beige aipocytes

    Hironori Waki

    Japanese Journal of Clinical Medicine   80 ( 4 ) 607 - 701   2022.04

    Introduction and explanation (scientific journal)  

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    ◆Other【 display / non-display 】

  • A Comprehensive Survey on Treatment, Care, and Lifestyle Experiences among Japanese Individuals With Diabetes

    Ihana-Sugiyama Noriko, Wakui-Kimura Akiko, Sugiyama Takehiro, Imai Kenjiro, Hosono Tomoko, Hotta Hiroko, Yamamoto Kouko, Aihara Masakazu, Aoyama Tomohisa, Sasako Takayoshi, Waki Hironori, Ohsugi Mitsuru, Ueki Kohjiro, Yamauchi Toshimasa

    Journal of the Japan Diabetes Society ( THE JAPAN DIABETES SOCIETY )  67 ( 11 ) 476 - 488   2024.11

    <p>Understanding the perspectives of patients with diabetes is crucial for accurately identifying important points for improving medical care and policies. In this study, we conducted a self-reported survey on experiences related to diabetes medical care and daily life, analyzing the results from 1,099 people with type 1 diabetes (T1DM) and 1,436 people with type 2 diabetes (T2DM). Over 90 % chose "physicians" as their primary consultants for diabetes at medical institutions, with a minority choosing non-doctors. The rate of treatment discontinuation was 3.2 % for T1DM and 8.7 % for T2DM due to a lack of understanding of the importance of treatment and financial constraints. Factors prompting a return to treatment were interactions with healthcare professionals, such as being called in and worsening health conditions. The proportion of patients who felt "heavily burdened" by medical costs was 33.8 % for T1DM and 13.4 % for T2DM. There was a higher rate of perceived societal prejudice against diabetes in younger patients and patients with T1DM, with 21.9 % of T1DM and 12.0 % of T2DM patients, indicating that prejudice exists among healthcare providers. There is a need for multidisciplinary involvement of patients and discussions to address specific challenges. Addressing the prejudice felt by patients should be a priority, starting with healthcare providers.</p>

    DOI CiNii Research

  • Vision Transformer–based Tinea Unguium Classification Approach Using Foot Images

    Miura Kakeru, Zou Min, Sato Takehiro, Waki Hironori, Kageyama Yoichi

    Proceedings of IIAE Annual Conference ( The Institute of Industrial Applications Engineers )  2024 ( 0 ) 67 - 68   2024

    DOI CiNii Research

  • CNN-SVM-Based Tinea Unguium Classification Approach to Telemedicine System

    Miura Kakeru, Zou Min, Sato Takehiro, Waki Hironori, Kageyama Yoichi

    Proceedings of IIAE Annual Conference ( The Institute of Industrial Applications Engineers )  2023 ( 0 ) 23 - 24   2023

    In recent years, the number of patients with diabetes mellitus has increased. Moreover, the prevalence of diabetes among older age groups in Japan is notably higher, indicating a growing proportion of patients with diabetes. Diabetic foot complications manifests in some patients with diabetes mellitus; hence, timely identification of the symptoms associated with diabetic feet is crucial for preventing severe complications. It is imperative for patients to observe their feet regularly; however, recognizing diabetic foot symptoms can be challenging for individuals without medical expertise owing to the variability of such symptoms. In this study, we focused on tinea unguium as a case type and utilized machine learning to classify images of tinea unguium and normal feet. The evaluation results showed that the combination of ResNet-50 and a support vector machine yielded the best performance when applied to a dataset of the acquired images of the nail regions the feet.

    DOI CiNii Research

  • CNN-SVM-Based Tinea Unguium Classification Approach to Telemedicine System

    三浦翔流, ZOU Min, 佐藤雄大, 脇裕典, 景山陽一

    産業応用工学会全国大会講演論文集(Web)   2023   2023

    J-GLOBAL

  • Effects of GLP-1 Receptor Agonist on Changes in the Gut Bacterium and the Underlying Mechanisms

      49 ( 1 ) 37 - 44   2022.06

    DOI CiNii Research

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Books 【 display / non-display 】

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Academic Awards Received 【 display / non-display 】

  • Young Investigator Award

    2017.10   The Japan Society of Diabetic Complications   Transcriptional and epigenetic regulation in adipocytes and its significance in glucose, lipid and energy homeostasis

    Winner： Hironori Waki

  • Society Award

    2017.09   The Japanese Constitutional Medicine   Transcriptional and epigenetic regulation in adipocytes and its significance in life-style diseases

    Winner： Hironori Waki

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Grant-in-Aid for Scientific Research 【 display / non-display 】

  • Integrated understanding of the regulation of energy metabolism by NFIA and treatment strategies for obesity

    Grant-in-Aid for Scientific Research(C)

    Project Year： 2024.04  -  2027.03 

  • Epigenetic Regulation of Adipocyte Progenitor Cells

    Grant-in-Aid for Challenging Research (Exploratory)

    Project Year： 2021.07  -  2023.03 

  • Epigenetic Regulation of Adipocyte Progenitor Cells

    Grant-in-Aid for Challenging Research (Exploratory)

    Project Year： 2021.07  -  2023.03 

  • Epigenetic Regulation of Adipocyte Progenitor Cells

    Grant-in-Aid for Challenging Research (Exploratory)

    Project Year： 2021.07  -  2023.03 

  • Epigenetic Regulation of Adipocyte Progenitor Cells

    Grant-in-Aid for Challenging Research (Exploratory)

    Project Year： 2021.07  -  2023.03  Investigator(s): Waki Hironori

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Presentations 【 display / non-display 】

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Academic Activity 【 display / non-display 】

  • Japan Association for Diabetes Education and Care

    2024.04
    -
    Now

    Deligate

  • Akita Univeristy Hospital

    2024.04
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    Now

    Deputy Hospital Director

  • Japan Society for the Study of Obesity

    2024.03
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    Now

    Education Committee Members

  • The Japan Society for the Study of Obesity

    2024.03
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    Now

    Auditor

  • Japan Society for the Study of Obesity

    2024.03
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    Now

    Chair of Young Committee

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Lifelong learning support results 【 display / non-display 】

  • The University of Tokyo Hospital, diabetes patient advocacy group "Kakehashi"

    Department of Diabetes and Metabolic Diseases, the University of Tokyo Hospital 

    2009.02
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    2021.05

  • The University of Tokyo Hospital, type 1 and mitochondrial diabetes patient advocacy group "Himawari"

    Department of Diabetes and Metabolic Diseases, the University of Tokyo Hospital 

    2009.02
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    2021.05

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Media Report 【 display / non-display 】

  • Prevention of complications of diabetes

    First Saturday of each month: from 17:25 to 17:30 Akita Broadcasting System (ABS) First Sunday of each month: from 17:25 to 17:30 Akita Asahi Broadcasting (AAB) Second Saturday of each month: from 13:55 to 14:00 Akita Television (AKT)

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