Cho, Hakusyo

写真a

Affiliation

School of Medicine, Department of Internal Medicine (Gastroenterology and Hepatology) (Shinanomachi)

Position

Assistant Professor/Senior Assistant Professor

Remarks

Po-sung Chu

Profile Summary 【 Display / hide

  • 台湾生まれで台湾台北育ち、26歳までに台湾国立台湾大学医学部において医師免許取得や臨床医学研修を含む医学教育を受けました。2007年2月(27歳)に日本国家医師試験を受け免許を取得し、同年4月から慶應義塾大学病院にて医師として勤務を始めました。臨床医としても研鑽を深めていき、出身の台湾や日本を含むアジア地域に多くの患者がウイルス性肝疾患、肝硬変や肝癌に苦しまれることに関心を持つようになりました。2009年より臨床勤務を継続しながら、同大学大学医学研究科(消化器内科学)に進学し、前任日比紀文教授、現金井隆典教授を始め、肝臓グループ(現同大学薬学部)齋藤英胤教授、海老沼浩利先生(現国際福祉大学病院消化器内科教授)、中本伸宏先生の指導のもと、肝臓免疫を中心に、肝線維化に関わる免疫細胞chemokine受容体CCR9の基礎研究やC型慢性肝炎ウイルスに対する免疫応答NKG2Dと治療効果に関わるヒト末梢血を用いた研究(研究実績1)を行いました。2014年6月より現在に至り、同大学病院消化器内科助教として、臨床の面ではウイルス性慢性肝炎における肝線維化、肝不全や肝発癌の機序解明、基礎の面では肝臓線維化の消退回復に関わる免疫学的機序解明について、臨床や研究、医学教育に精力を注いでいます。

Academic Background 【 Display / hide

  • 1997.09
    -
    2004.06

    National Taiwan University, Department of Medicine

    Taiwan, Province of China, University, Graduated, Other

  • 2009.04
    -
    2013.03

    Keio University, Graduate School for Medical Research

    Graduate School, Completed, Doctoral course

Academic Degrees 【 Display / hide

  • 学士(医学), National Taiwan University, 2004.06

  • 博士(医学), Keio University, 2015.03

    C-C Motif Chemokine Receptor 9 Positive Macrophages Activate Hepatic Stellate Cells and Promote Liver Fibrosis in Mice

Licenses and Qualifications 【 Display / hide

  • 日本 医師免許, 2007.04

  • 日本肝臓学会 専門医, 2015.04

  • 日本消化器病学会 専門医, 2016.01

 

Research Areas 【 Display / hide

  • Life Science / Gastroenterology

Research Keywords 【 Display / hide

  • Gastroenterology Hepatology Immunology

 

Papers 【 Display / hide

  • Bacteriophage therapy against pathological Klebsiella pneumoniae ameliorates the course of primary sclerosing cholangitis

    Ichikawa M., Nakamoto N., Kredo-Russo S., Weinstock E., Weiner I.N., Khabra E., Ben-Ishai N., Inbar D., Kowalsman N., Mordoch R., Nicenboim J., Golembo M., Zak N., Jablonska J., Sberro-Livnat H., Navok S., Buchshtab N., Suzuki T., Miyamoto K., Teratani T., Fujimori S., Aoto Y., Konda M., Hayashi N., Chu P.S., Taniki N., Morikawa R., Kasuga R., Tabuchi T., Sugimoto S., Mikami Y., Shiota A., Bassan M., Kanai T.

    Nature Communications (Nature Communications)  14 ( 1 )  2023.12

     View Summary

    Primary sclerosing cholangitis (PSC) is characterized by progressive biliary inflammation and fibrosis. Although gut commensals are associated with PSC, their causative roles and therapeutic strategies remain elusive. Here we detect abundant Klebsiella pneumoniae (Kp) and Enterococcus gallinarum in fecal samples from 45 PSC patients, regardless of intestinal complications. Carriers of both pathogens exhibit high disease activity and poor clinical outcomes. Colonization of PSC-derived Kp in specific pathogen-free (SPF) hepatobiliary injury-prone mice enhances hepatic Th17 cell responses and exacerbates liver injury through bacterial translocation to mesenteric lymph nodes. We developed a lytic phage cocktail that targets PSC-derived Kp with a sustained suppressive effect in vitro. Oral administration of the phage cocktail lowers Kp levels in Kp-colonized germ-free mice and SPF mice, without off-target dysbiosis. Furthermore, we demonstrate that oral and intravenous phage administration successfully suppresses Kp levels and attenuates liver inflammation and disease severity in hepatobiliary injury-prone SPF mice. These results collectively suggest that using a lytic phage cocktail shows promise for targeting Kp in PSC.

  • IL-15-producing splenic B cells play pathogenic roles in the development of autoimmune hepatitis

    Fujimori S., Chu P.S., Teratani T., Harada Y., Suzuki T., Amiya T., Taniki N., Kasuga R., Mikami Y., Koda Y., Ichikawa M., Tabuchi T., Morikawa R., Yamataka K., Noguchi F., Tsujikawa H., Kurebayashi Y., Sakamoto M., Kanai T., Nakamoto N.

    JHEP Reports (JHEP Reports)  5 ( 7 )  2023.07

     View Summary

    Background & Aims: B-cell depletion therapy with an anti-CD20 is an effective treatment strategy for patients with refractory autoimmune hepatitis (AIH). However, the mechanisms underlying B-cell action are unclear. Methods: Herein, we used the adeno-associated virus IL-12 model, in which hepatic IL-12 expression triggers liver injuries characteristic of AIH. We also analysed the clinical samples of patients with AIH. Results: B-cell depletion using anti-CD20 or splenectomy was found to improve liver functions and decrease the cytotoxic CD8+ T-cell (cytotoxic T lymphocyte [CTL]) count in the liver. This improvement was reversed by the adoptive transfer of splenic B cells derived from AAV IL-12-treated mice to splenectomised mice as it caused the hepatic CTL count to increase. RNA-sequencing analysis identified IL-15 as a key factor in pathogenic B cells, which promotes CTL expansion and subsequent migration to the liver via the CXCL9/CXCR3 axis. Indeed, IL-15 neutralisation ameliorated hepatitis by suppressing splenic and hepatic CTLs in vivo. The close distribution of B220+ B cells and CD8+ T cells in the spleen of AIH mice suggested mutual interactions. Mechanistically, IFNγ and CD40L/CD40 signalling were indispensable for the expression of IL-15 in B cells, and in vitro co-culture experiments revealed that splenic CD40L+CD8+ T cells promoted IL-15 production in B cells, which led to CTL expansion. In patients with AIH, high serum IL-15 concentration and IL-15+ B-cell counts, positively correlating with serum alanine aminotransferase levels, support translation and potential therapeutic targeting in human AIH. Conclusions: This investigation elucidated the roles of IL-15-producing splenic B cells that occur in concert with pathogenic CD8+ T cells during the development of AIH. Impact and Implications: IL-15-producing B cells were shown to exacerbate experimental AIH via cytotoxic T lymphocyte expansion. CD40L+CD8+ T cells promoted IL-15 expression in B cells, indicating the mutual interaction of both cells. High serum IL-15 concentrations, IL-15+ B-cell counts, and CD40L+IL-15Rα+CD8+ T-cell counts were confirmed in the blood of patients with AIH.

  • Myeloid TLR4 signaling promotes post-injury withdrawal resolution of murine liver fibrosis

    Takimoto Y., Chu P.s., Nakamoto N., Hagihara Y., Mikami Y., Miyamoto K., Morikawa R., Teratani T., Taniki N., Fujimori S., Suzuki T., Koda Y., Ishihara R., Ichikawa M., Honda A., Kanai T.

    iScience (iScience)  26 ( 3 )  2023.03

     View Summary

    The fate of resolution of liver fibrosis after withdrawal of liver injury is still incompletely elucidated. Toll-like receptor 4 (TLR4) in tissue fibroblasts is pro-fibrogenic. After withdrawal of liver injury, we unexpectedly observed a significant delay of fibrosis resolution as TLR4 signaling was pharmacologically inhibited in vivo in two murine models. Single-cell transcriptome analysis of hepatic CD11b+ cells, main producers of matrix metalloproteinases (MMPs), revealed a prominent cluster of restorative Tlr4-expressing Ly6c2-low myeloid cells. Delayed resolution after gut sterilization suggested its microbiome-dependent nature. Enrichment of a metabolic pathway linking to a significant increase of bile salt hydrolase-possessing family Erysipelotrichaceae during resolution. Farnesoid X receptor-stimulating secondary bile acids including 7-oxo-lithocholic acids upregulated MMP12 and TLR4 in myeloid cells in vitro. Fecal material transplant in germ-free mice confirmed phenotypical correlations in vivo. These findings highlight a pro-fibrolytic role of myeloid TLR4 signaling after injury withdrawal and may provide targets for anti-fibrotic therapy.

  • Concurrent de novo Thymoma-associated Paraneoplastic Type 1 Autoimmune Hepatitis and Pure Red Cell Aplasia after Thymectomy: A Case Report and Literature Review

    Sakata R., Chu P.S., Kawaida M., Emoto K., Sakurai M., Nishida R., Asakura K., Morikawa R., Taniki N., Kataoka K., Kanai T., Nakamoto N.

    Internal Medicine (Internal Medicine)  62 ( 2 ) 243 - 249 2023

    ISSN  09182918

     View Summary

    The precise manipulation of immune tolerance is the holy grail of immunotherapies for both autoimmunity and cancer immunity. Thymomas are well known to be associated with autoimmune diseases. The exact mechanism by which autoreactivity is induced after thymectomy remains to be elucidated. We herein present the case of a 50-year-old lady with concurrent de novo type 1 autoimmune hepatitis (AIH) and pure red cell aplasia (PRCA), 1 month after undergoing a successful total thymectomy for combined squamous cell carcinoma and thymoma (Masaoka stage II). Corticosteroids yielded short-term effects for both AIH and PRCA. Literature on thymoma-associated AIH, an extremely rare immune-related comorbidity, was also reviewed.

  • Successful Case of Deceased Donor Liver Transplant for Polycystic Liver Disease

    Sugimoto H., Oshima Y., Oba Y., Ikuma D., Sekine A., Mizuno H., Yamanouchi M., Hasegawa E., Suwabe T., Chu P.S., Hasegawa Y., Obara H., Sawa N., Ubara Y.

    Transplantation Proceedings (Transplantation Proceedings)  54 ( 10 ) 2779 - 2783 2022.12

    ISSN  00411345

     View Summary

    A 58-year-old woman was admitted to hospital for deceased donor liver transplant. Her liver volume, measured by computed tomography, had reached 22,764 cm3 and she was bedridden with performance status 3 because of abdominal distention. The Model for End-Stage Liver Disease score was 24 with exception points. The final weight of the removed liver after cystic fluid puncture was 14 kg. The patient recovered well after transplant and was discharged on postoperative day 43 with a weight of 41 kg and performance status of 1.

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

Reviews, Commentaries, etc. 【 Display / hide

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

  • Analyses and applications of novel anti-fibrotic treatment for cirrhosis via the gut-liver axis

    2022.04
    -
    2025.03

    MEXT,JSPS, Grant-in-Aid for Scientific Research, 基盤研究(C), Principal investigator

  • Mechanism of the Plasticity of Innate Immunity during Metabolic Re-compensation in Liver Cirrhosis

    2019.04
    -
    2021.03

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

  • Mechanisms of induction of liver cirrhosis-resolving restorative macrophages

    2016.04
    -
    2019.03

    文部科学省 日本学術振興会, Grant-in-Aid for Scientific Research, Pos-sung Chu, Research grant, Principal investigator

Awards 【 Display / hide

  • Bristol-Myers Award

    2014.11, 日本肝臓学会

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

  • Liver Forum in Kyoto優秀演題賞

    2014.04

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

 

Courses Taught 【 Display / hide

  • LECTURE SERIES, INTERNAL MEDICINE (GASTROENTEROLOGY)

    2023

  • LECTURE SERIES, INTERNAL MEDICINE (GASTROENTEROLOGY)

    2022

  • LECTURE SERIES, INTERNAL MEDICINE (GASTROENTEROLOGY)

    2021

  • LECTURE SERIES, INTERNAL MEDICINE (GASTROENTEROLOGY)

    2020

  • LECTURE SERIES, INTERNAL MEDICINE (GASTROENTEROLOGY)

    2019