KEIO RESEARCHERS INFORMATION SYSTEM

Profile Summary 【 Display / hide 】

Profile Summary 【 Display / hide 】

• 私たちは、胎児への薬物分布を制御する胎盤関門について研究しています。主に安全性の問題から、妊娠中疾患は薬物治療の貢献が不十分です。薬物の胎児影響は実験動物を用いて評価せざるを得ませんが、薬物の胎児移行性を規定する胎盤関門輸送体の中にはヒトだけにあるものや、ヒトとラットの間で発現量が異なるものがあり、ヒト胎児移行性の予測を困難にしています。私たちは、胎盤関門輸送体機能の種差を解明することなどを通じ、ヒト胎児中薬物濃度の予測精度を高め、妊婦で使用可能な薬物の選択肢を増やすことを目指しています。今後の医療は疾患の素因をあらかじめ摘み取る先制医療へとシフトしていきます。生活習慣病や精神・神経疾患の素因が形成される胎児の環境を直接的に制御するのは、胎盤関門です。胎盤関門機能の理解から、将来の疾患発症リスクを軽減する先制医療を実現させることが大きな目標です。

Other Affiliation 【 Display / hide 】

Other Affiliation 【 Display / hide 】

• Dean, Graduate School of Pharmaceutical Sciences

Career 【 Display / hide 】

Career 【 Display / hide 】

• 2001.04

  -

  2005.09

  Assistant Professor, Faculty of Pharmaceutical Sciences, Toyama Medical and Pharmaceutical University

• 2005.10

  -

  2006.03

  Assistant Professor, Faculty of Pharmaceutical Sciences, University of Toyama

• 2006.04

  -

  2008.12

  Postdoctoral Fellow, David Geffen School of Medicine, University of California, Los Angeles (UCLA)

• 2009.01

  -

  2011.03

  Senior Assistant Professor, Faculty of Pharmacy, Keio University

• 2011.04

  -

  2016.03

  Associate Professor, Faculty of Pharmacy, Keio University

display all >>

Academic Background 【 Display / hide 】

Academic Background 【 Display / hide 】

• 1998.03

  Tohoku University, Faculty of Pharmaceutical Science, 薬学科

  University, Graduated

• 2000.03

  Tohoku University, Graduate School, Division of Pharmaceutical Sciences, 分子生命薬学専攻

  Graduate School, Completed, Master's course

• 2001.03

  Tohoku University, Graduate School, Division of Pharmaceutical Sciences, 生命薬学専攻

  Graduate School, Withdrawal before completion, Doctoral course

Academic Degrees 【 Display / hide 】

Academic Degrees 【 Display / hide 】

• Ph.D.(Pharmaceutical Sciences), Tohoku University, Dissertation, 2004.01

Licenses and Qualifications 【 Display / hide 】

Licenses and Qualifications 【 Display / hide 】

• 薬剤師, 1999.02

Research Areas 【 Display / hide 】

Research Areas 【 Display / hide 】

• Life Science / Clinical pharmacy

Books 【 Display / hide 】

Books 【 Display / hide 】

• 基礎と臨床の両側面からみた 胎盤学

  日本胎盤学会 (編集) 登美 斉俊, メジカルビュー, 2019.12

  Scope: 物質交換,  Contact page： 80-84

• 薬の生体内運命 改訂7版

  丸山一雄 (編集) 登美斉俊, ネオメディカル, 2017.03

  Scope: 排泄,  Contact page： 112-134

• スタンダード薬学シリーズⅡ 6 医療薬学 Ⅵ. 薬の生体内運命

  日本薬学会 (編集) 崔 吉道, 登美斉俊, 東京化学同人, 2016.12

  Scope: 胎盤関門の構造・機能と薬物の胎児への移行,  Contact page： 63-65

• 薬剤学実験法必携マニュアル - Pharmaceutical Scientistのために Ⅱ　生物薬剤学

  日本薬剤学会出版委員会 (編集) 登美斉俊, 西村友宏, 南江堂, 2014.04

  Scope: 血液胎盤関門,  Contact page： 138-145

• 薬の生体内運命 改訂5版

  中島恵美 (編集) 登美斉俊, ネオメディカル, 2013.03

  Scope: 薬の運命,  Contact page： 12-18

display all >>

Papers 【 Display / hide 】

Papers 【 Display / hide 】

• Characterizing Apixaban Pharmacokinetics Through Physiologically-Based Pharmacokinetic Modeling: Critical Role of Biliary Secretion and Enterohepatic Circulation in Humans

  Tsuchitani T., Kou W., Tomi M., Sugiyama Y.

  Cpt Pharmacometrics and Systems Pharmacology 15 ( 1 ) e70163 2026.01

  　View Summary

  Apixaban, a factor Xa inhibitor, is a direct oral anticoagulant with a well-balanced elimination; it is eliminated evenly via feces, urine (with no active secretion), and as metabolites after oral administration. The common understanding is that biliary secretion and enterohepatic circulation (EHC) of apixaban are limited in humans, and that fecal excretion may be attributable to intestinal secretion. However, a decrease in apixaban blood concentration with activated charcoal coadministration in humans suggests possible involvement of EHC. This study aimed to evaluate the contribution of biliary excretion, EHC, and intestinal secretion to apixaban pharmacokinetics (PK) using a physiologically-based pharmacokinetic (PBPK) model. A top-down analysis was performed using blood concentration and mass balance data from healthy volunteers. Model parameters were optimized using the Cluster-Gauss Newton method (CGNM), followed by the bootstrap method. The model accurately described observed data and indicated moderate to high biliary secretion relative to metabolic clearance. Simulated biliary secretion into the duodenum well predicted the biliary secretion data in humans (< 1% of dose at 8 h post-dose). Virtual knockout of EHC resulted in a shortened half-life from 8.7 to 2.9 h, and 17% and 55% decrease in area under the concentration curve (AUC) and fecal excretion after intravenous dosing, respectively, confirming the significant contribution of biliary excretion and EHC. The model also accurately described apixaban PK with activated charcoal coadministration at 2 or 6 h post-dose. Although further experimental validation (e.g., sandwich-cultured hepatocytes) would strengthen these findings, our study demonstrates that biliary secretion and EHC play a substantial role in apixaban elimination and disposition in humans.

  • Access to Document (DOI)

• Rat-Specific Expression of Placental MATE1 Contributes to Species Difference in Fetal Transfer of Metformin and 1-Methyl-4-Phenylpyridinium.

  Suzuki A, Noguchi S, Tsuchitani T, Sakamoto R, Yamauchi A, Ishinabe T, Hashimoto R, Nakaguchi Y, Sakai M, Imayoshi N, Ishimoto T, Kato Y, Shirasaka Y, Katakura S, Maruyama T, Nishimura T, Tomi M

  Molecular pharmaceutics 22 ( 12 ) 7412 - 7422 2025.11

  ISSN  1543-8384

  　View Summary

  Metformin readily crosses the human placenta. However, the fetal-to-maternal plasma concentration ratio (F/M ratio) of metformin has been reported to be as low as 0.057 in rats. This study investigated the underlying mechanisms of these interspecies differences by examining the expression and function of candidate transporters, organic cation transporter 3 (OCT3/SLC22A3) and multidrug and toxin extrusion protein 1 (MATE1/SLC47A1), in the placenta across species. Expression analysis at gene and protein levels using RNA-sequencing and absolute quantification by LC-MS/MS revealed minimal species differences in placental OCT3 expression (less than 4-fold). In contrast, MATE1 showed almost exclusive expression in the rat placental labyrinth, but minimal or undetectable levels were observed in samples prepared from human placental villi and mouse placental labyrinth. To evaluate the function of the placental MATE1, we compared the placental transfer of two dual substrates of MATE1 and OCT3, metformin and 1-methyl-4-phenylpyridinium (MPP⁺), in pregnant rats and mice in the presence and absence of pyrimethamine, a MATE1 inhibitor. The pyrimethamine was dosed to reach the plasma concentration, which specifically inhibits MATE1 based on the measured IC<inf>50</inf> of pyrimethamine to rat MATE1 and OCT3, which were 0.015 and 100 μM, respectively. The F/M ratios of metformin and MPP⁺ in the absence of pyrimethamine were half or less in rats compared to mice. Notably, preadministration of pyrimethamine increased the F/M ratios of metformin and MPP⁺ by approximately 50% in rats but not mice. These findings demonstrate that functional placental MATE1 expression is specific to rats, which, in part, contributes to the low fetal transfer of cationic compounds compared with other species. This is of significant concern, as it suggests that nonclinical developmental and reproductive toxicity studies of MATE1 substrate drugs in rats may underestimate fetal exposure and toxicity when extrapolated to humans.

  • Access to Document (DOI)

• Fetal ezrin expression affects macrophages and regulatory T cells in mouse placental decidua

  Nishimura T., Mizokami R., Yamanaka M., Takahashi M., Yoshida Y., Ogawa Y., Noguchi S., Tomi M.

  Biochemical and Biophysical Research Communications 735   150842 2024.11

  Research paper (scientific journal), Accepted,  ISSN  0006291X

  　View Summary

  Ezrin is a cross-linker protein between membrane proteins and cytosolic actin, abundantly expressed in the placenta among the ERM protein family. Ezrin gene knockout mice exhibit fetal growth restriction after gestational day (GD) 15.5. This study aimed to clarify the effect of ezrin on immune cells that influence fetal growth and immune tolerance. Ezrin heterozygous knockout (Ez+/−) mice were interbred, and the gene expressions and immune cell distributions in the placentas of wild-type (Ez+/+) and ezrin knockout (Ez−/−) fetuses were analyzed. IL-6 expression in the placenta of Ez−/− fetuses was significantly higher than in Ez+/+ fetuses at GD 15.5. The mRNA expression of IL-6 in the uterine decidua attached to Ez−/− fetuses was higher compared to that attached to Ez+/+ fetuses but not in the junctional zone and labyrinth. Classical M1 and M2 macrophages in the decidua were analyzed by flow cytometry using CD86 and CD206 as markers. M1 macrophages increased in the decidua attached to Ez−/− mice compared to Ez+/+ mice, while M2 macrophages did not increase. CD4-positive T cells showed a reduction in the decidua attached to Ez−/− fetuses. Further analysis involved the subcutaneous administration of tacrolimus in pregnant Ez+/− mice from GD 8.5 to GD 15.5, which prevented the decrease in fetal body weight and decidual CD4-positive T cells in Ez−/− mice at GD 15.5. These results suggest that impaired expression of fetoplacental-derived ezrin induces inflammatory conditions in the uterine decidua through M1 polarization of macrophages, increased IL-6, and decreased CD4-positive T cells, including Treg cells.

  • Access to Document (DOI)

• Conversion of Olmesartan to Olmesartan Medoxomil, A Prodrug that Improves Intestinal Absorption, Confers Substrate Recognition by OATP2B1

  Fukazawa N., Nishimura T., Orii K., Noguchi S., Tomi M.

  Pharmaceutical Research (Pharmaceutical Research)  41 ( 5 ) 849 - 861 2024.05

  ISSN  07248741

  　View Summary

  Purpose: Olmesartan medoxomil (olmesartan-MX), an ester-type prodrug of the angiotensin II receptor blocker (ARB) olmesartan, is predominantly anionic at intestinal pH. Human organic anion transporting polypeptide 2B1 (OATP2B1) is expressed in the small intestine and is involved in the absorption of various acidic drugs. This study was designed to test the hypothesis that OATP2B1-mediated uptake contributes to the enhanced intestinal absorption of olmesartan-MX, even though olmesartan itself is not a substrate of OATP2B1. Methods: Tetracycline-inducible human OATP2B1- and rat Oatp2b1-overexpressing HEK 293 cell lines (hOATP2B1/T-REx-293 and rOatp2b1/T-REx-293, respectively) were established to characterize OATP2B1-mediated uptake. Rat jejunal permeability was measured using Ussing chambers. ARBs were quantified by liquid chromatography-tandem mass spectrometry. Results: Significant olmesartan-MX uptake was observed in hOATP2B1/T-REx-293 and rOatp2b1/T-REx-293 cells, whereas olmesartan uptake was undetectable or much lower than olmesartan-MX uptake, respectively. Furthermore, olmesartan-MX exhibited several-fold higher uptake in Caco-2 cells and greater permeability in rat jejunum compared to olmesartan. Olmesartan-MX uptake in hOATP2B1/T-REx-293 cells and in Caco-2 cells was significantly decreased by OATP2B1 substrates/inhibitors such as 1 mM estrone-3-sulfate, 100 µM rifamycin SV, and 100 µM fluvastatin. Rat Oatp2b1-mediated uptake and rat jejunal permeability of olmesartan-MX were significantly decreased by 50 µM naringin, an OATP2B1 inhibitor. Oral administration of olmesartan-MX with 50 µM naringin to rats significantly reduced the area under the plasma concentration–time curve of olmesartan to 76.9%. Conclusion: Olmesartan-MX is a substrate for OATP2B1, and the naringin-sensitive transport system contributes to the improved intestinal absorption of olmesartan-MX compared with its parent drug, olmesartan.

  • Access to Document (DOI)

• Involvement of GAT2/Slc6a13 in hypotaurine uptake at fetal-facing plasma membrane of syncytiotrophoblasts at mid-to-late gestation in rats and mice

  Nishimura T., Araki H., Higuchi K., Noguchi S., Saito K., Hara K., Yagishita H., Akashi R., Obata S., Tomi M.

  Placenta (Placenta)  147   59 - 67 2024.03

  ISSN  01434004

  　View Summary

  Introduction: Hypotaurine, a precursor to taurine, is known for its antioxidant properties and is prominently present in fetal plasma and the placenta. Our previous research revealed that ezrin-knockout mice experience fetal growth retardation, coinciding with reduced hypotaurine levels in fetal plasma. This study aims to elucidate the expression and role of hypotaurine transporters within the placenta. Methods: We employed quantitative RT-PCR to measure mRNA expression of GAT transporter family members in the placenta during mid-to-late gestation. LC/MS/MS was used to analyze the distribution of hypotaurine in different placental subregions. Immunohistochemistry was utilized to examine the localization of GAT2 in mice. Placental hypotaurine uptake from fetal circulation was studied via umbilical perfusion in rats. Results: Among hypotaurine transporters, GAT2 exhibited increased mRNA and protein expression in murine placenta during mid-to-late gestation. Notably, GAT2/Slc6a13 mRNA and hypotaurine were most concentrated in the labyrinth of murine placenta. In contrast, enzymes responsible for hypotaurine synthesis, such as cysteine dioxygenase, cysteine sulfinic acid decarboxylase, and 2-aminoethanethiol dioxygenase, showed minimal expression in the labyrinth. These findings suggest that GAT2 is a key determinant of hypotaurine levels in the placental labyrinth. Immunohistochemical examination unveiled that GAT2 was predominantly localized on the fetal-facing plasma membrane within syncytiotrophoblasts, which co-localized with ezrin. In rat umbilical perfusion experiments, the GAT2/3 and TauT inhibitor, SNAP-5114, significantly reduced hypotaurine extraction from fetal circulation to the placenta. Discussion: The results suggest that GAT2 plays a pivotal role in the concentrative uptake of hypotaurine from fetal plasma within syncytiotrophoblasts of the placenta.

  • Access to Document (DOI)

display all >>

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

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

• Prediction model for transplacental drug exposure to the human fetus based on species differences in placental transporters and plasma unbound concentrations

  Tomi, Masatoshi

  科学研究費補助金研究成果報告書 2023

• Regulation of pharmacokinetics during pregnancy by placental exosomes

  Tomi, Masatoshi

  科学研究費補助金研究成果報告書 2021

• Significance of a balanced tryptophan diet for supporting fetal growth

  Tomi, Masatoshi

  科学研究費補助金研究成果報告書 2020

• Functional expression of sensing factors against maternal osmotic stress in the placenta

  Tomi, Masatoshi

  科学研究費補助金研究成果報告書 2017

• Food guide for pregnant women based on placental permeability of ingredients

  Tomi, Masatoshi

  科学研究費補助金研究成果報告書 2016

display all >>

Reviews, Commentaries, etc. 【 Display / hide 】

Reviews, Commentaries, etc. 【 Display / hide 】

• 【胎盤を多角的に理解する】低分子薬物と生物学的製剤の胎盤透過制御

  登美 斉俊

  産科と婦人科 ((株)診断と治療社)  92 ( 5 ) 489 - 493 2025.05

  ISSN  0386-9792

  　View Summary

  ＜文献概要＞薬物の胎児移行性の指標である胎児血/母体血濃度比は,胎盤関門に発現するトランスポーターや受容体など,担体を介した胎盤透過の影響を強く受ける.たとえば,高分子である生物学的製剤は,サイズの大きさから多くは胎盤透過できないが,Fc受容体に認識される抗体医薬品は胎盤をトランスサイトーシスで透過するため,胎児移行性が高い.低分子薬物と高分子の生物学的製剤のそれぞれについて,胎盤関門を介した薬物の胎児移行制御メカニズムを紹介する.

• 【胎盤の母児支援機構とその評価】ファーマコメトリクスを応用したヒト胎児薬物曝露量予測

  黒沢 健, 登美 斉俊, 千葉 康司

  細胞 ((株)ニュー・サイエンス社)  56 ( 3 ) 158 - 162 2024.03

  ISSN  1346-7557

  　View Summary

  妊婦薬物治療は,母体及び胎児に対するリスクとベネフィットを考慮して行う。そのため胎児曝露量は重要であり,出産時の母体血及び臍帯血の薬物濃度比(in vivo F/M比)は,有用な指標となる。母体・胎児薬物移行性評価法としてヒト胎盤に薬物灌流を行うex vivoヒト胎盤灌流試験がある。ヒト胎盤に薬物の灌流を実験的に行い,母体-胎児間の薬物移行を検討する。大半の薬剤でex vivo試験で得られた母体-胎児濃度比(ex vivo F/M比)と,in vivo F/M比が一致することが報告されているが,digoxinなど一部の薬物では一致しない。筆者らは,既報のex vivoヒト胎盤灌流試験にファーマコメトリクス,すなわちモデリング・シミュレーション手法を応用し,この原因を明らかにすると共に,胎児曝露量を予測可能とした。本稿ではこの新たなヒト胎児曝露量予測法についてdigoxinを例に紹介する。(著者抄録)

• 【妊娠・授乳中の薬剤の安全性について科学する】薬物の胎児移行性評価と薬物療法

  登美 斉俊

  Precision Medicine ((株)北隆館)  4 ( 10 ) 918 - 921 2021.09

  ISSN  2434-3625

  　View Summary

  薬物の胎児移行性を評価し、その機構を理解するには、定常状態における胎児血/母体血濃度比を基準とすることが重要である。定常状態における濃度比に影響するのは薬物の脂溶性やタンパク結合率に限らず、むしろトランスポーターを介した透過クリアランスによる影響が大きい。本稿では、妊婦に用いられる薬物として血糖降下薬や甲状腺機能亢進症治療薬、ジゴキシンに焦点を当て、定常状態における濃度比に基づく胎児移行性評価と、胎児移行に果たす胎盤トランスポーターの役割、胎児への影響について概説する。(著者抄録)

• Faculty challenges during the SARS-CoV-2 pandemic and the results of student questionnaires for the implementation of online and face-to-face classes

  Ishikawa Satoko, Inoue Kae, Tomi Masatoshi

  Japanese Journal of Pharmaceutical Education (Japan Society for Pharmaceutical Education)  5 ( 0 ) n/a 2021

  ISSN  2432-4124

  　View Summary

  <p>Review of the challenges posed by the SARS-CoV-2 pandemic at Keio University Faculty of Pharmacy. We shared the latest information needed to conduct online classes with faculty and staff, held seminars on using learning management systems, creating video content, and for copyright adherence of educational materials. For freshmen of the Faculty of Pharmacy, an online communication session was held in April of 2020 and a subsequent environment for conducting face-to-face classes once a week was implemented from June of 2020. At our campus, students were able to participate more actively as college students, have interactions with their peers, ask questions, and consult with the faculty. From questionnaires about online classes, problems facing the students were identified and presented to our faculty for purposes of improving learning content. The number of students who chose the option "I don't have an opportunity to talk with my friends" tends to decrease as the academic year of education rises. Hence, more consideration should be given particularly to the first-year students. All students tended to have relatively good impressions about online classes due to the efficiency and ability for repeated viewing of lecture content. We would like to utilize the knowledge acquired from the past 10 months to provide more effective classes and further enhance the educational impact at the Faculty of Pharmacy.</p>

  • Access to Document (DOI)
  • CiNii Research

• 【周産期の薬】産科編　総論　薬物の経胎盤透過

  登美 斉俊

  周産期医学 ((株)東京医学社)  50 ( 増刊 ) 46 - 48 2020.12

  ISSN  0386-9881

display all >>

Presentations 【 Display / hide 】

Presentations 【 Display / hide 】

• MCT1はヒト胎盤バリアモデルにおいてプロピオン酸の双方向輸送を促進するが、MCT4は促進しない

  山本 耕平, 緑川 凜, 土谷 聡耀, 野口 幸希, 堀 武志, 梶 弘和, 登美 斉俊

  [Domestic presentation]  日本薬学会第146年会 (大阪) , 

  2026.03

  , 

  Oral presentation (general)

• In vivo・ex vivoにおけるIgG経胎盤透過を説明可能な生理学的薬物速度論モデルの構築

  藤﨑 舞友子, 土谷 聡耀, 野口 幸希, 登美 斉俊

  [Domestic presentation]  日本薬学会第146年会 (大阪) , 

  2026.03

  , 

  Poster presentation

• Placental MATE1 expression in rats explains species differences in fetal transfer of organic cations

  Tomi M, Suzuki A, Sakamoto R, Hashimoto R, Yamauchi A, Sakai M, Nishimura T, Tsuchitani T, Noguchi S

  [International presentation]  Asian Federation for Pharmaceutical Sciences Conference 2025 (Sydney) , 

  2025.12

  , 

  Oral presentation (general)

• Identification of syncytiotrophoblast-specific transporter genes and their protein expression in mouse placenta

  Inagaki K, Noguchi S, Takei R, Ishinabe T, Nishimura T, Tsuchitani T, Tomi M

  [International presentation]  Asian Federation for Pharmaceutical Sciences Conference 2025 (Sydney) , 

  2025.12

  , 

  Oral presentation (general)

• Single-cell transcriptomic analysis of Wnt/β-catenin-mediated differentiation pathways in mouse trophoblast stem cells

  Ishinabe T, Noguchi S, Suganuma N, Nishimura T, Tsuchitani T, Tomi M

  [International presentation]  Asian Federation for Pharmaceutical Sciences Conference 2025 (Sydney) , 

  2025.12

  , 

  Oral presentation (general)

display all >>

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

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

• Ex vivo-in silicoハイブリッドによるヒト胎児薬物移行の新解析プラットフォーム構築

  2024.04

  -

  2027.03

  Grants-in-Aid for Scientific Research, Grant-in-Aid for Scientific Research (B), No Setting

  　View Summary

  妊婦における薬物治療を有効かつ安全に行うためには、定常状態ヒト胎児/母体血漿中薬物濃度比（F/M比）は必須だが、情報に乏しい。本研究では、出産後のヒト胎盤のex vivo灌流に、生理学的薬物動態モデルを用いたin silicoでのパラメータ推定を組み合わせ、従来のex vivoヒト胎盤灌流のみでは実測できなかった低膜透過性薬物のF/M比推定手法（ex vivo-PBPKハイブリッド解析）を確立することを目指す。本研究は、多くの薬物のヒトF/M比が不明な現状を改善し、妊婦と胎児でのアンメットメディカルニーズに応える意義を有している。

• Prediction model for transplacental drug exposure to the human fetus based on species differences in placental transporters and plasma unbound concentrations

  2021.04

  -

  2024.03

  Keio University, Grants-in-Aid for Scientific Research, Tomi Masatoshi, Grant-in-Aid for Scientific Research (B), No Setting

  　View Summary

  Although the prediction accuracy of the steady-state fetal/maternal plasma concentration ratio (F/M ratio) of some low-membrane-permeability drugs by human placental perfusion has been low, the present study demonstrated that the steady-state F/M ratio of can be estimated by combining the originally developed pharmacokinetic model. Moreover, we clarified that one of the reasons for the lower F/M ratio in rats compared to humans is the species difference in protein binding. This can be overcome by employing the unbound F/M ratio in rats. Furthermore, we observed that the specific expression of MATE1 in rat placenta and the rodent-specific localization of placental MDR1 contribute to the species differences in the fetal transfer of substrate drugs.

• Regulation of pharmacokinetics during pregnancy by placental exosomes

  2020.07

  -

  2022.03

  Keio University, Grants-in-Aid for Scientific Research, Tomi Masatoshi, Challenging Research (Exploratory), No Setting

  　View Summary

  Syncytin-2, a molecule specifically expressed in the placenta, has membrane fusion capacities and contributes to the barrier formation through syncytialization. In this study, it is indicated that the uptake of JEG-3 cell-derived exosome to human hepatic HepG2 cells was significantly enhanced when the expression of syncytin-2 in JEG-3 cells was induced. The placenta-specific miRNA is detected from HepG2 cells exposed to JEG-3 cell-derived exosomes, implying that exosomal syncytin-2 is capable to mediate cell-to-cell communication through the exosome. However, the expression of MFSD2A, a receptor of syncytin-2, is found not to be constitutively expressed in the mouse liver. Therefore, it is necessary to further confirm whether syncytin-2-expressing exosome is preferably binds to hepatic cells. We also found that MFSD2A involves in the supply of docosahexaenoic acid to the fetus.

• Significance of a balanced tryptophan diet for supporting fetal growth

  2018.04

  -

  2021.03

  MEXT,JSPS, Grant-in-Aid for Scientific Research, Tomi Masatoshi, Grant-in-Aid for Scientific Research (B), Principal investigator

  　View Summary

  The purpose of the present study was to clarify the transporters mediating the fetal transfer of tryptophan and examine the importance of an adequate supply of tryptophan into the fetus. This study described the amount and localization of LAT1 protein, a transporter for large neutral amino acids including tryptophan, at the placental barrier. It is also observed that the tissue distribution of LAT1 substrate is suppressed by an increase of LAT1-substrate amino acids in the plasma. For serotonin, we have clarified OCTN1 protein accepts it as a substrate and is expressed at the placental barrier at term. However, the effect of tryptophan imbalance in the diet was negligible in the plasma concentration of amino acids.

• Functional expression of sensing foctors against maternal osmotic stress in the placenta

  2015.04

  -

  2018.03

  Keio University, NISHIMURA Tomohiro, Grant-in-Aid for Scientific Research (C), No Setting

  　View Summary

  Placenta is an interface between mother and fetus and it has a role of nutrients transfer. The placenta has the function mitigating the osmotic stress exposed from maternal blood. Part of amino acid is transferred via amino acid transport system A from mother to fetus in the placenta. In this study, we clarified that expression of the system A molecule can be more quickly increased in response to the osmotic stress than other molecules and we investigated how the system A molecules is induced by hypertonic stress.

display all >>

Awards 【 Display / hide 】

Awards 【 Display / hide 】

• 2019 Top Reviewer

  2019, Journal of Pharmaceutical Sciences

  Type of Award： Honored in official journal of a scientific society, scientific journal

• 2018 Top Reviewer

  2018, Journal of Pharmaceutical Sciences

  Type of Award： Honored in official journal of a scientific society, scientific journal

• 2017 Top Reviewer

  2017, Journal of Pharmaceutical Sciences

  Type of Award： Honored in official journal of a scientific society, scientific journal

• 日本薬剤学会奨励賞

  2015, The Academy of Pharmaceutical Science and Technology, Japan, 関門トランスポーターによる薬物組織分布制御機構の研究

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

• 学部長賞

  2015, 慶應義塾大学薬学部

  Type of Award： Keio commendation etc.

display all >>

Courses Taught 【 Display / hide 】

Courses Taught 【 Display / hide 】

• STUDY OF MAJOR FIELD: (PHARMACEUTICS)

  2025

• SEMINAR: (PHARMACEUTICS)

  2025

• RESEARCH FRONTIERS IN BIOMEDICAL SCIENCE

  2025

• RESEARCH FOR BACHELOR'S THESIS 1

  2025

• PHYSICAL PHARMACY

  2025

display all >>