フィトケミカルの生理機能におけるcGMPの関与を中心に研究。
cGMPの幅広い生体保護作用に着目し、これらを介した
機能性食品の研究や、新たな治療標的の探索等を実施。


My research focuses on the role of cGMP in the physiological effects of phytochemicals.
Our group previously identified several molecules including Tollip and demonstrated that those signaling pathways-induced by cGMP play crucial role in the resilience of the human body. To understand the physiological role of the cGMP in the beneficial effect of several compounds including phytochemicals, we use several disease mouse models including orthotopic tumor implantation model (Osteosarcoma, MPM, Pancreatic cancer, Lung cancer, breast cancer, etc) and other disease models (Obesity, SLE, IBD, ARDS, IgAN, NASH, PAH, Parkinson’s disease, Rheumatoid arthritis). Based on our findings, our recent clinical study found that GT-gH (our proposed polyphenols combination based by cGMP induction) suppressed weight gain and BMI increase in human subjects (UMIN000040109 Placebo-controlled, randomized, double-blind). My goal is to establish the novel strategy to prevent and treat difficult disease.
キーワード：cGMP、フィトケミカル、ケミカルバイオロジー、免疫学、腫瘍学
2021.12～2022.06.

cGMPの生体調節作用
2018.04～2022.06
cGMPの生体保護作用の解明とその調節法の開発.

主要著書

1.	藤村由紀, 熊添基文, 立花宏文 , 緑茶の機能性と薬理 緑茶カテキンセンシングと機能性増強技術, 機能性食品と薬理栄養, 2019.08.
2.	立花宏文, 山下修矢, 熊添基文, 個人に適した効果的な摂取条件等を特定する手法の開発及び摂取条件等を普及するためのモデル体制の構築(茶)第1章 緑茶の機能性感知調節作用の研究開発 , 農林水産省農林水産技術会議事務局研究成果 (農林水産技術会議事務局研究成果), J-GLOBAL ID：201502257943898251, 2015.02.
3.	熊添基文, 立花 宏文, 茶カテキンの活性発現機序に基づいた新たながん治療戦略, バイオサイエンスとインダストリー, 2018.11.

主要原著論文

1.	Kumazoe Motofumi, Miyamoto Emi, Oka Chihiro, Kondo Miyuki, Yoshitomi Ren, Onda Hiroaki, Shimada Yu, Fujimura Yoshinori, Tachibana Hirofumi., miR-12135 ameliorates liver fibrosis accompanied with downregulation of ITGA11., iScience, 10.1016/j.isci.2023.108730, 108730, 2023.12, [URL].
2.	Yamashita Mai*, Kumazoe Motofumi* (Equal Contribution), Onda Hiroaki, Hiroi Shun, Shimada Yu, Fujimura Yoshinori, Tachibana Hirofumi., PPAR/PDK4 pathway is involved in the anticancer effects of cGMP in pancreatic cancer., Biochem Biophys Res Commun., 10.1016/j.bbrc.2023.06.043., 672, 154-160, 2023.09.
3.	Kumazoe Motofumi, Ogawa Fumiyo, Hikida Ai, Shimada Yu, Yoshitomi Ren, Watanabe Ryoya, Onda Hiroaki, Fujimura Yoshinori, Tachibana Hirofumi., Plant miRNA osa-miR172d-5p suppressed lung fibrosis by targeting Tab1., Sci Rep, 10.1038/s41598-023-29188-6, 2128, 2023.02, [URL].
4.	Kumazoe Motofumi, Fujimura Yoshinori, Yoshitomi Ren, Shimada Yu, Tachibana Hirofumi., Fustin, a Flavanonol, Synergically Potentiates the Anticancer Effect of Green Tea Catechin Epigallocatechin-3-O-Gallate with Activation of the eNOS/cGMP Axis., Journal of agricultural and food chemistry, 10.1021/acs.jafc.1c07567, 70, 11, 3458-3466, 2022.03.
5.	Kumazoe Motofumi, Takamatsu Kanako, Horie Fuyumi, Yoshitomi Ren, Hamagami Hiroki, Tanaka Hiroshi, Fujimura Yoshinori, Tachibana Hirofumi., Methylated (-)-epigallocatechin 3-O-gallate potentiates the effect of split vaccine accompanied with upregulation of Toll-like receptor 5., Scientific reports, 11, 1, 23101-23101, 2021.11.
6.	Kumazoe Motofumi, Tanaka Yasutake, Yoshitomi Ren, Marugame Yuki, Lee Kwan-Woo, Onda Hiroaki, Fujimura Yoshinori , Yonekura Madoka, Shimamoto Yasuyo, Tachibana Hirofumi., Glucosyl-hesperidin enhances the cyclic guanosine monophosphate-inducing effect of a green tea polyphenol EGCG., Journal of natural medicines, 10.1007/s11418-021-01538-6, 75, 4, 1037-1042, 2021.09.
7.	Tanaka Yasutake*, Kumazoe Motofumi* (Equal Contribution), Onda Hiroaki, Fujimura Yoshinori, Tachibana Hirofumi., Time-dependent increase of plasma cGMP concentration followed by oral EGCG administration in mice., Food Bioscience, https://doi.org/10.1016/j.fbio.2021.101017, 41, 101017-101017, 2021.06.
8.	Kumazoe Motofumi, Kadomatsu Mai, Bae Jaehoon, Otsuka Yushi, Fujimura Yoshinori, Tachibana Hirofumi., Src Mediates Epigallocatechin-3-O-Gallate-Elicited Acid Sphingomyelinase Activation., Molecules (Basel, Switzerland), 10.3390/molecules25225481, 25, 22, 2020.11.
9.	Kumazoe Motofumi, Hiroi Shun, Tanimoto Yousuke, Miyakawa Jyunichi, Yamanouchi Maasa, Suemasu Yumi, Yoshitomi Ren, Murata Motoki, Fujimura Yoshinori, Takahashi Takashi, Tanaka Hiroshi, Tachibana Hirofumi., Cancer cell selective probe by mimicking EGCG., Biochemical and biophysical research communications, 10.1016/j.bbrc.2020.03.021, 525, 4, 974-981, 2020.05.
10.	Bae Jaehoon*, Kumazoe Motofumi* (Equal Contribution), Takeuchi Chieri, Hidaka Shiori, Fujimura Yoshinori, Tachibana Hirofumi., Epigallocatechin-3-O-gallate induces acid sphingomyelinase activation through activation of phospholipase C., Biochemical and biophysical research communications, 10.1016/j.bbrc.2019.09.102, 520, 1, 186-191, 2019.11.
11.	Kumazoe Motofumi, Yamashita Mai, Nakamura Yuki, Takamatsu Kanako, Bae Jaehoon, Yamashita Shuya, Yamada Shuhei, Onda Hiroaki, Nojiri Takashi, Kangawa Kenji, Tachibana Hirofumi., Green Tea Polyphenol EGCG Upregulates Tollip Expression by Suppressing Elf-1 Expression., JOURNAL OF IMMUNOLOGY, 10.4049/jimmunol.1601822, 199, 9, 3261-3269, 2017.11.
12.	Tsukamoto Shuntaro*, Kumazoe Motofumi* (Equal Contribution), Huang Yuhui, Lesnick Connie, Kay E. Neil, Shanafelt D. Tait, Tachibana Hirofumi., SphK1 inhibitor potentiates the anti-cancer effect of EGCG on leukaemia cells., BRITISH JOURNAL OF HAEMATOLOGY, 10.1111/bjh.14119, 178, 1, 155-158, 2017.07.
13.	Kumazoe Motofumi, Takai Mika, Hiroi Shun, Takeuchi Chieri, Kadomatsu Mai, Nojiri Takashi, Onda Hiroaki, Bae Jaehoon, Huang Yuhui, Takamatsu Kanako, Yamashita Shuya, Kangawa Kenji, Tachibana Hirofumi., The FOXO3/PGC-1 beta signaling axis is essential for cancer stem cell properties of pancreatic ductal adenocarcinoma., JOURNAL OF BIOLOGICAL CHEMISTRY, 10.1074/jbc.M116.772111, 292, 26, 10813-10823, 2017.06.
14.	Kumazoe Motofumi, Takai Mika, Bae Jaehoon, Hiroi Shun, Huang Yuhui, Takamatsu Kanako, Won Yeong Seon, Yamashita Mai, Hidaka Shiori, Yamashita Shuya, Yamada Shuhei, Murata Motoki, Tsukamoto Shuntaro, Tachibana Hirofumi., FOXO3 is essential for CD44 expression in pancreatic cancer cells., ONCOGENE, 10.1038/onc.2016.426, 36, 19, 2643-2654, 2017.05.
15.	Kumazoe Motofumi, Takai Mika, Hiroi Shun, Takeuchi Chieri, Yamanouchi Maasa, Nojiri Takashi, Onda Hiroaki, Bae Jaehoon, Huang Yuhui, Takamatsu Kanako, Yamashita Shuya, Yamada Shuhei, Kangawa Kenji, Takahashi Takashi, Tanaka Hiroshi, Tachibana Hirofumi., PDE3 inhibitor and EGCG combination treatment suppress cancer stem cell properties in pancreatic ductal adenocarcinoma., SCIENTIFIC REPORTS, 10.1038/s41598-017-02162-9, 7, 1, 1917, 2017.05.
16.	Kumazoe Motofumi, Nakamura Yuki, Yamashita Mai, Suzuki Takashi, Takamatsu Kanako, Huang Yuhui, Bae Jaehoon, Yamashita Shuya, Murata Motoki, Yamada Shuhei, Shinoda Yuki, Yamaguchi Wataru, Toyoda Yui, Tachibana Hirofumi., Green Tea Polyphenol Epigallocatechin-3-gallate Suppresses Toll-like Receptor 4 Expression via Up-regulation of E3 Ubiquitin-protein Ligase RNF216., JOURNAL OF BIOLOGICAL CHEMISTRY, 10.1074/jbc.M116.755959, 292, 10, 4077-4088, 2017.03.
17.	Huang Yuhui*, Kumazoe Motofumi* (Equal Contribution), Bae Jaehoon, Yamada Shuhei, Takai Mika, Hidaka Shiori, Yamashita Shuya, Kim Yoonhee, Won Yeongseon, Murata Motoki, Tsukamoto Shuntaro, Tachibana Hirofumi., Green tea polyphenol epigallocatechin-O-gallate induces cell death by acid sphingomyelinase activation in chronic myeloid leukemia cells., ONCOLOGY REPORTS, 10.3892/or.2015.4086, 34, 3, 1162-1168, 2015.09.
18.	Kumazoe Motofumi, Fujimura Yoshinori, Hidaka Shiori, Kim Yoonhee, Murayama Kanako, Takai Mika, Huang Yuhui , Yamashita Shuya, Murata Motoki, Miura Daisuke, Wariishi Hiroyuki, Maeda-Yamamoto Mari, Tachibana Hirofumi., Metabolic Profiling-based Data-mining for an Effective Chemical Combination to Induce Apoptosis of Cancer Cells., SCIENTIFIC REPORTS, 10.1038/srep09474, 5, 2015.03.
19.	Kumazoe Motofumi, Tsukamoto Shuntaro, Lesnick Connie, Kay E. Neil, Yamada Koji, Shanafelt D. Tait, Tachibana Hirofumi., Vardenafil, a clinically available phosphodiesterase inhibitor, potentiates the killing effect of EGCG on CLL cells., BRITISH JOURNAL OF HAEMATOLOGY, 168, 4, 610-613, 2015.02.
20.	Kumazoe Motofumi, Kim Yoonhee, Bae Jaehoon, Takai Mika, Murata Motoki, Suemasu Yumi, Sugihara Kaori, Yamashita Shuya, Tsukamoto Shuntaro, Huang Yuhui, Nakahara Kanami, Yamada Koji, Tachibana Hirofumi. , Phosphodiesterase 5 inhibitor acts as a potent agent sensitizing acute myeloid leukemia cells to 67-kDa laminin receptor-dependent apoptosis., FEBS LETTERS, 10.1016/j.febslet.2013.07.041, 587, 18, 3052-3057, 2013.09.
21.	Kumazoe Motofumi, Sugihara Kaori, Tsukamoto Shuntaro, Huang Yuhui, Tsurudome Yukari, Suzuki Takashi, Suemasu Yumi, Ueda Naoki, Yamashita Shuya, Kim Yoonhee, Yamada Koji, Tachibana Hirofumi., 67-kDa laminin receptor increases cGMP to induce cancer-selective apoptosis., JOURNAL OF CLINICAL INVESTIGATION, 10.1172/JCI64768, 123, 2, 787-799, 2013.02.

主要総説, 論評, 解説, 書評, 報告書等

1.	Motofumi Kumazoe, Yoshinori Fujimura, Hirofumi Tachibana, 67-kDa Laminin Receptor Mediates the Beneficial Effects of Green Tea Polyphenol EGCG, Current Pharmacology Reports, https://doi.org/10.1007/s40495-020-00228-3, 2020.01.
2.	熊添基文, 立花 宏文, 緑茶カテキンセンシング機構とその応用展開-カテキンパワーの引き出し方., 化学と生物, 2016.03.

主要学会発表等

1.	Kumazoe M, Yoshinori F, Tachibana H., cGMP mediates beneficial effect of EGCG., International Conference on Food Factors, 2019.11.
2.	Kumazoe M, Tachibana H., EGCG induces cancer-specific cell death via the sensing receptor-mediated cGMP production., Functional and Medical Foods, Bioactive Compounds and Biomarkers, 2015.11.
3.	Kumazoe M, Tachibana H., 67-kDa laminin receptor and cGMP induced cancer-selective apoptosis., The 6th International Meeting on cGMP, 2013.06.
4.	Kumazoe M, Tachibana H., EGCG induces cancer-specific cell death via the sensing receptor-mediated cGMP production., International Conference on Tea., 2013.12.
5.	熊添基文, 高井美佳, 廣井舜, 高松香菜子, 門松舞, 山下麻衣, 藤村由紀, 立花宏文 , Epigallocatechin-3-O-gallate(EGCG)/Phosphodiesterase3阻害剤併用は膵臓がんのがん幹細胞性を阻害する, 日本農芸化学会 2020年度大会, 2020.03.
6.	熊添基文，高松香菜子, 藤村由紀, 立花宏文, メチル化EGCGによるスプリット型ワクチンの作用増強, 2021年度西日本・中四国・関西支部 合同大会, 2021.09.

特許出願・取得

所属学会名

学会大会・会議・シンポジウム等における役割