Characterizations of Polyion Complex Formed at Hydrogel Adhesion Interface
Hibiki Shiimura, Takuya Nishimura, Yuki Yokoi, Masahiro Yoshida, Yoshinori Katsuyama, Kiminori Nakamura, Takayuki Kurokawa
Macromolecules, American Chemical Society (ACS), 14 Apr. 2025, [Peer-reviewed]
Scientific journal

Potential consequences of phototoxicity on cell function during live imaging of intestinal organoids
Yuki Yokoi, Ryu Nakamura, Shuya Ohira, Shota Takemi, Tokiyoshi Ayabe, Kiminori Nakamura
PLOS ONE, 19, 11, e0313213, e0313213, Public Library of Science (PLoS), 15 Nov. 2024, [Peer-reviewed]
Scientific journal, Live imaging visualizes the structure, dynamics, and function of cells and tissues to reveal the molecular mechanisms, and has contributed to the advancement of life science. In live imaging, it has been well known that there is a trade-off between higher-resolution analysis and cell damage caused by light illumination, i.e., phototoxicity. However, despite the risk of unknowingly distorting experimental results, phototoxicity is an unresolved issue in live imaging because overall consequences occurring inside cells due to phototoxicity remains unknown. Here, we determined the molecular process of phototoxicity-induced cell damage systematically under low- and high-dose light illumination conditions by analyzing differential gene expression using RNA-sequencing in a three-dimensional organoid of small intestinal epithelial cells, enteroid. The low-dose light illumination already induced various abnormalities in functional molecules involved in the response to reactive oxygen species generated by the excitation of fluorescent dyes, intracellular metabolism, mitosis, immune responses, etc., at mRNA expression level. Together with the behavior toward apoptosis caused by high-dose light illumination, the light dose-dependent progression of intracellular damage was revealed. About visible impairment of intestinal epithelial function, failures in both the structure-forming ability of enteroids and Paneth cell granule secretion were observed under high-dose light illumination, while the drug efflux was not disturbed despite abnormal drug efflux transporter mRNA expression. Based on the gene expression profiles, we comprehensively clarified phenomena in the cells at mRNA level that cannot be recognized both morphologically and functionally during live imaging, further providing a new insight into the risk of phototoxicity. This study warns from the aspect of mRNA expression that awareness of phototoxic artifacts is needed when analyzing cellular function and the mechanism in live imaging.

Association between oral frailty and Prevotella percentage in the oral microbiota of community-dwelling older adults who participated in the CHEER Iwamizawa project, Japan.
Chizuru Kimura, Kazuhito Miura, Yutaka Watanabe, Haruhisa Baba, Kimiya Ozaki, Akira Hasebe, Tokiyoshi Ayabe, Kiminori Nakamura, Shinji Nakaoka, Katsuhiko Ogasawara, Teppei Suzuki, Hiroshi Saito, Takashi Kimura, Akiko Tamakoshi, Yutaka Yamazaki
Journal of oral rehabilitation, 08 Jun. 2024, [Peer-reviewed], [International Magazine]
English, Scientific journal, BACKGROUND: Prevotella bacteria are associated with inherent diseases of the oral cavity, such as periodontal disease, and systemic diseases. Oral frailty (OF) has been associated with nursing necessity and death. However, the relationship between OF and oral microbiota has not been fully clarified. OBJECTIVE: This cross-sectional study investigated the association between OF and Prevotella percentage in the oral microbiota of community-dwelling older adults. METHODS: Oral bacteria species from saliva were identified in 208 community-dwelling older individuals aged ≥60 years in Japan. The proportion of Prevotella in the oral microbiota was classified into three tertile groups, and its relationship with each test item for OF (number of remaining teeth, masticatory performance, oral diadochokinesis, tongue pressure, difficulties eating tough foods, difficulties swallowing tea or soup, number of applicable OF judgement items, and existence of OF) was examined using ordinal logistic regression analysis. RESULTS: The Prevotella proportions were classified into lower, middle and upper groups, comprising 70, 69 and 69 participants, respectively. The three groups showed a significant relationship between the number of remaining teeth (odds ratio [OR]: 0.946, 95% confidence interval [CI]: 0.915-0.977), masticatory performance (OR: 0.897, 95% CI: 0.844-0.953), number of applicable OF judgement items (OR: 1.477, 95% CI: 1.14-1.915), and existence of OF (OR: 4.194, 95% CI: 1.519-11.576). CONCLUSION: The proportion of Prevotella in oral microbiota was high in individuals with OF. Among the older adults, the type of oral microbiota and systemic diseases may be related to the examination and management of oral function decline.

Development of an Evaluation System Using Intestinal Organoids for Drug Efflux Transport Analysis by an Imaging Approach
Chihiro Koseki, Takehiko Ishikawa, Yuki Sato, Mikiko Shimada, Yuki Yokoi, Kiminori Nakamura, Naoyuki Honma, Takanori Moriyama, Hitoshi Kashiwagi, Mitsuru Sugawara
Journal of Pharmaceutical Sciences, Elsevier BV, Jun. 2024, [Peer-reviewed]
Scientific journal

Effects of exposure to the neonicotinoid pesticide clothianidin on α-defensin secretion and gut microbiota in mice
Sakura YONOICHI, Yukako HARA, Yuya ISHIDA, Asuka SHODA, Mako KIMURA, Midori MURATA, Sarika NUNOBIKI, Makiko ITO, Ayano YOSHIMOTO, Youhei MANTANI, Toshifumi YOKOYAMA, Tetsushi HIRANO, Yoshinori IKENAKA, Yuki YOKOI, Tokiyoshi AYABE, Kiminori NAKAMURA, Nobuhiko HOSHI
Journal of Veterinary Medical Science, Japanese Society of Veterinary Science, 2024, [Peer-reviewed]
Scientific journal

A Basic Study of the Effects of Mulberry Leaf Administration to Healthy C57BL/6 Mice on Gut Microbiota and Metabolites
Li Gan, Yuga Inamura, Yu Shimizu, Yuki Yokoi, Yuki Ohnishi, Zihao Song, Yasuhiro Kumaki, Takashi Kikukawa, Makoto Demura, Masaaki Ito, Tokiyoshi Ayabe, Kiminori Nakamura, Tomoyasu Aizawa
Metabolites, 13, 9, 1003, 1003, MDPI AG, 10 Sep. 2023, [Peer-reviewed]
Scientific journal, Mulberry leaves contain α-glucosidase inhibitors, which have hypoglycemic effects and are considered functional foods. However, few reports have covered the effects of mulberry leaf components on normal gut microbiota and gut metabolites. Herein, gut microbiota analysis and NMR-based metabolomics were performed on the feces of mulberry leaf powder (MLP)-treated mice to determine the effects of long-term MLP consumption. Gut microbiota in the mouse were analyzed using 16S-rRNA gene sequencing, and no significant differences were revealed in the diversity and community structure of the gut microbiota in the C57BL/6 mice with or without MLP supplementation. Thirty-nine metabolites were identified via 1H-NMR analysis, and carbohydrates and amino acids were significantly (p < 0.01–0.05) altered upon MLP treatment. In the MLP-treated group, there was a marked increase and decrease in maltose and glucose concentrations, respectively, possibly due to the degradation inhibitory activity of oligosaccharides. After 5 weeks, all amino acid concentrations decreased. Furthermore, despite clear fluctuations in fecal saccharide concentrations, short-chain fatty acid production via intestinal bacterial metabolism was not strongly affected. This study provides the knowledge that MLP administration can alter the gut metabolites without affecting the normal gut microbiota, which is useful for considering MLP as a healthy food source.

Antimicrobial Properties and Mode of Action of Cryptdin-4, a Mouse α-Defensin Regulated by Peptide Redox Structures and Bacterial Cultivation Conditions
Yi Wang, Yuchi Song, Shaonan Yan, Rina Hiramine, Yuki Ohnishi, Yuki Yokoi, Kiminori Nakamura, Takashi Kikukawa, Tokiyoshi Ayabe, Tomoyasu Aizawa
Antibiotics, 12, 6, 1047, 1047, MDPI AG, 14 Jun. 2023, [Peer-reviewed]
Scientific journal, Cryptdin-4 (crp4) is an enteric α-defensin derived from mice, and is a main mediator of immunity to oral infections and a determinant of the composition of the intestinal microbiota. Structurally, crp4 exists in two states: the oxidized form (crp4oxi), constrained by three invariant disulfide bonds, and the reduced form (crp4red) with six free thiol groups, both of which exist in the intestinal tract. In this study, the antibacterial mechanisms of crp4 in both forms under aerobic and anaerobic conditions were investigated using Escherichia coli (E. coli), an anaerobic facultative bacterium, as a model. Fluorescent dye studies revealed that both crp4oxi and crp4red exhibited antimicrobial activity against cells cultured under aerobic conditions via rapid membrane depolarization. Furthermore, the antioxidant treatment experiments suggested that only crp4oxi exhibited antimicrobial activity by the induction and accumulation of reactive oxygen species (ROS). However, under anaerobic culture conditions, the ability of both forms to disrupt the function of bacterial membranes decreased and activity was greatly reduced, but crp4red maintained some antimicrobial activity. This activity may be due to the inhibition of intracellular functions by DNA binding. Altogether, these data indicate that, according to its redox structure and the environmental redox conditions, crp4 could perform different antimicrobial activities via different mechanisms.

Application of Benchtop NMR for Metabolomics Study Using Feces of Mice with DSS-Induced Colitis
Zihao Song, Yuki Ohnishi, Seiji Osada, Li Gan, Jiaxi Jiang, Zhiyan Hu, Hiroyuki Kumeta, Yasuhiro Kumaki, Yuki Yokoi, Kiminori Nakamura, Tokiyoshi Ayabe, Kazuo Yamauchi, Tomoyasu Aizawa
Metabolites, 13, 5, 611, 611, MDPI AG, 28 Apr. 2023, [Peer-reviewed]
Scientific journal, Nuclear magnetic resonance (NMR)-based metabolomics, which comprehensively measures metabolites in biological systems and investigates their response to various perturbations, is widely used in research to identify biomarkers and investigate the pathogenesis of underlying diseases. However, further applications of high-field superconducting NMR for medical purposes and field research are restricted by its high cost and low accessibility. In this study, we applied a low-field, benchtop NMR spectrometer (60 MHz) employing a permanent magnet to characterize the alterations in the metabolic profile of fecal extracts obtained from dextran sodium sulfate (DSS)-induced ulcerative colitis model mice and compared them with the data acquired from high-field NMR (800 MHz). Nineteen metabolites were assigned to the 60 MHz 1H NMR spectra. Non-targeted multivariate analysis successfully discriminated the DSS-induced group from the healthy control group and showed high comparability with high-field NMR. In addition, the concentration of acetate, identified as a metabolite with characteristic behavior, could be accurately quantified using a generalized Lorentzian curve fitting method based on the 60 MHz NMR spectra.

Shorter sleep time relates to lower human defensin 5 secretion and compositional disturbance of the intestinal microbiota accompanied by decreased short-chain fatty acid production
Yu Shimizu, Ryodai Yamamura, Yuki Yokoi, Tokiyoshi Ayabe, Shigekazu Ukawa, Koshi Nakamura, Emiko Okada, Akihiro Imae, Takafumi Nakagawa, Akiko Tamakoshi, Kiminori Nakamura
Gut Microbes, 15, 1, Informa UK Limited, 21 Mar. 2023, [Peer-reviewed]
Scientific journal

Decreased Paneth cell α-defensins promote fibrosis in a choline-deficient L-amino acid-defined high-fat diet-induced mouse model of nonalcoholic steatohepatitis via disrupting intestinal microbiota
Shunta Nakamura, Kiminori Nakamura, Yuki Yokoi, Yu Shimizu, Shuya Ohira, Mizu Hagiwara, Zihao Song, Li Gan, Tomoyasu Aizawa, Daigo Hashimoto, Takanori Teshima, Andre J. Ouellette, Tokiyoshi Ayabe
Scientific Reports, 13, 1, Springer Science and Business Media LLC, 09 Mar. 2023, [Peer-reviewed]
Scientific journal, Abstract

Nonalcoholic steatohepatitis (NASH) is a chronic liver disease characterized by fibrosis that develops from fatty liver. Disruption of intestinal microbiota homeostasis, dysbiosis, is associated with fibrosis development in NASH. An antimicrobial peptide α-defensin secreted by Paneth cells in the small intestine is known to regulate composition of the intestinal microbiota. However, involvement of α-defensin in NASH remains unknown. Here, we show that in diet-induced NASH model mice, decrease of fecal α-defensin along with dysbiosis occurs before NASH onset. When α-defensin levels in the intestinal lumen are restored by intravenous administration of R-Spondin1 to induce Paneth cell regeneration or by oral administration of α-defensins, liver fibrosis is ameliorated with dissolving dysbiosis. Furthermore, R-Spondin1 and α-defensin improved liver pathologies together with different features in the intestinal microbiota. These results indicate that decreased α-defensin secretion induces liver fibrosis through dysbiosis, further suggesting Paneth cell α-defensin as a potential therapeutic target for NASH.

Associations between Maternal Diet, Human Milk Macronutrients, and Breast-Fed Infant Growth during the First Month of Life in the SMILE Iwamizawa in Japan.
Yosuke Komatsu, Yasuaki Wada, Fuka Tabata, Satomi Kawakami, Yasuhiro Takeda, Kiminori Nakamura, Tokiyoshi Ayabe, Koshi Nakamura, Takashi Kimura, Akiko Tamakoshi
Nutrients, 15, 3, 28 Jan. 2023, [Peer-reviewed], [International Magazine]
English, Scientific journal, Maternal diet may affect human milk macronutrients, but it remains to be elucidated whether this is also influential in infant growth. This study aimed to examine (1) how maternal diet influences human milk macronutrients, and (2) to what extent the variation in milk macronutrients affects infant growth during the first month of life. In 71 Japanese lactating women, maternal dietary information was collected from the brief-type self-administered diet history questionnaire, and anthropometry of mother-infant dyads was collected from medical records. Macronutrients in milk were analyzed by a Human Milk Analyzer. Maternal retinol intake was associated with the carbohydrate content in human milk at 1-month postpartum (standardized β coefficient: 0.287; p = 0.038). Moreover, the energy content in human milk was associated with an increase in the weight standard deviation score based on the WHO growth standard at 1 month of age (standardized β coefficient: 0.399; p = 0.046). Nevertheless, the milk macronutrient was not associated with the risk of infant growth abnormalities. In conclusion, a part of the maternal diet impacts macronutrient contents in human milk, but milk macronutrients have a limited effect on infant growth only within the normal growth curve during the first month of life.

Efficient recombinant production of mouse-derived cryptdin family peptides by a novel facilitation strategy for inclusion body formation.
Yuchi Song, Yi Wang, Shaonan Yan, Kiminori Nakamura, Takashi Kikukawa, Tokiyoshi Ayabe, Tomoyasu Aizawa
Microbial cell factories, 22, 1, 9, 9, 13 Jan. 2023, [Peer-reviewed], [International Magazine]
English, Scientific journal, BACKGROUND: A number of antimicrobial peptides (AMPs) hold promise as new drugs owing to their potent bactericidal activity and because they are often refractory to the development of drug resistance. Cryptdins (Crps) are a family of antimicrobial peptides found in the small intestine of mice, comprising six isoforms containing three sets of disulfide bonds. Although Crp4 is actively being investigated, there have been few studies to date on the other Crp isoforms. A prerequisite for detailed characterization of the other Crp isoforms is establishment of efficient sample preparation methods. RESULTS: To avoid degradation during recombinant expression of Crps in E. coli, co-expression of Crps with the aggregation-prone protein human α-lactalbumin (HLA) was used to promote the formation of stable inclusion bodies. Using this method, the production of Crp4 and Crp6 by the BL21 strain was effective, but the expression of other Crp isoforms was not as efficient. The results of a cell-free system study suggested that Crps were degraded, even though a substantial amounts of Crps were synthesized. Therefore, using the Origami™ B strain, we were able to significantly increase the expression efficiency of Crps by promoting the formation of erroneous intermolecular disulfide bonds between HLA and Crps, thereby promoting protein aggregation and inclusion body formation, which prevented degradation. The various Crp isoforms were successfully refolded in vitro and purified using reversed-phase HPLC. In addition, the yield was further improved by deformylation of formyl-Crps. We measured the antibacterial activity of Crps against both Gram-positive and Gram-negative bacteria. Each Crp isoform exhibited a completely different trend in antimicrobial activity, although conformational analysis by circular dichroism did not reveal any significant steric differences. CONCLUSION: In this study, we established a novel and efficient method for the production of the cryptdin family of cysteine-containing antimicrobial peptides. Additionally, we found that there were notable differences in the antibacterial activities of the various Crp family members. The expression system established in this study is expected to provide new insights regarding the mechanisms underlying the different antibacterial activities of the Crp family of peptides.

Efficient and simple genetic engineering of enteroids using mouse isolated crypts for investigating intestinal functions
Shuya Ohira, Yuki Yokoi, Tokiyoshi Ayabe, Kiminori Nakamura
Biochemical and Biophysical Research Communications, 637, 153, 160, Elsevier BV, Dec. 2022, [Peer-reviewed]
Scientific journal

Reactive granulopoiesis depends on T-cell production of IL-17A and neutropenia-associated alteration of gut microbiota.
Xuanzhong Chen, Daigo Hashimoto, Ko Ebata, Shuichiro Takahashi, Yu Shimizu, Ryuga Shinozaki, Yuta Hasegawa, Ryo Kikuchi, Hajime Senjo, Kazuki Yoneda, Zixuan Zhang, Shinpei Harada, Eiko Hayase, Takahide Ara, Hiroyuki Ohigashi, Yoichiro Iwakura, Kiminori Nakamura, Tokiyoshi Ayabe, Takanori Teshima
Proceedings of the National Academy of Sciences of the United States of America, 119, 48, e2211230119, 29 Nov. 2022, [Peer-reviewed], [International Magazine]
English, Scientific journal, Granulopoiesis in the bone marrow adjusts cellular output as demand for neutrophils changes. Reactive granulopoiesis is induced by profound neutropenia, but its mechanism remains to be clarified. We herein explored its mechanisms using mouse models of syngeneic hematopoietic stem cell transplantation (SCT) and 5-fluorouracil-induced neutropenia. After SCT, T cell production of IL-17A was up-regulated. Neutrophil recovery was significantly delayed in IL-17A-deficient or T cell-deficient RAG1-/- mice, and adoptive transfer of wild-type (WT) T cells facilitated neutrophil engraftment. Gut decontamination with oral antibiotics suppressed T cell production of IL-17A and impaired neutrophil recovery. Transplantation of fecal microbiota collected from neutropenic, not naive, mice promoted neutrophil recovery in these mice, suggesting that neutropenia-associated microbiota had a potential to stimulate reactive granulopoiesis. Our study uncovered a cross talk between gut microbiota and neutropenia after SCT and chemotherapy.

Hemodynamic response to intestinal pH stimulation measured with spectroscopic video imaging
Tsukasa Funane, Yuki Yokoi, Masashi Kikuchi, Ryuga Shinozaki, Tokiyoshi Ayabe, Hirokazu Atsumori, Ayako Nishimura, Kiminori Nakamura, Akihiko Kandori
Biomedical Physics & Engineering Express, IOP Publishing, 11 Nov. 2022, [Peer-reviewed]
Scientific journal, Abstract

To investigate the relationship between the gut and skin (gut-skin axis), head skin hemodynamic responses to gut stimulation including the injection of acetic acid in nude mice were measured by spectroscopic video imaging, which was calculated using a modified Beer-Lambert formula. The relationship with blood proteins was also analyzed. The blood volume changes in three mice injected with acetic acid were highly reproducible in the mathematical model equation. Four proteins correlated with blood volume changes were all related to immunity. These results suggest that intestinal pH can alter the blood volume in the skin and induce immune-related responses.

Oral frailty and carriage of oral Candida in community‐dwelling older adults (Check‐up to discover Health with Energy for senior Residents in Iwamizawa; CHEER Iwamizawa)
Haruhisa Baba, Yutaka Watanabe, Kazuhito Miura, Kimiya Ozaki, Takae Matsushita, Miyako Kondoh, Kazutaka Okada, Akira Hasebe, Tokiyoshi Ayabe, Kiminori Nakamura, Shinji Nakaoka, Katsuhiko Ogasawara, Teppei Suzuki, Hiroshi Saito, Takashi Kimura, Akiko Tamakoshi, Yutaka Yamazaki
Gerodontology, 39, 1, 49, 58, Wiley, Mar. 2022, [Peer-reviewed]
Scientific journal

Potent bactericidal activity of reduced cryptdin-4 derived from its hydrophobicity and mediated by bacterial membrane disruption
Yuji Sato, Yi Wang, Yuchi Song, Weiming Geng, Shaonan Yan, Kiminori Nakamura, Takashi Kikukawa, Makoto Demura, Tokiyoshi Ayabe, Tomoyasu Aizawa
Amino Acids, 54, 2, 289, 297, Springer Science and Business Media LLC, Feb. 2022, [Peer-reviewed]
Scientific journal

Ingestion of miso regulates immunological robustness in mice
Kunihiko Kotake, Toshihiko Kumazawa, Kiminori Nakamura, Yu Shimizu, Tokiyoshi Ayabe, Takahiro Adachi
PLOS ONE, 17, 1, e0261680, e0261680, Public Library of Science (PLoS), Jan. 2022, [Peer-reviewed]
Scientific journal, In Japan, there is a long history of consumption of miso, a fermented soybean paste, which possesses beneficial effects on human health. However, the mechanism behind these effects is not fully understood. To clarify the effects of miso on immune cells, we evaluated its immunomodulatory activity in mice. Miso did not alter the percentage of B and T cells in the spleen; however, it increased CD69⁺ B cells, germinal center B cells and regulatory T cells. Anti-DNA immunoglobulin M antibodies, which prevent autoimmune disease, were increased following ingestion of miso. Transcriptome analysis of mouse spleen cells cultured with miso and its raw material revealed that the expression of genes, including interleukin (IL)-10, IL-22 and CD86, was upregulated. Furthermore, intravital imaging of the small intestinal epithelium using a calcium biosensor mouse line indicated that miso induced Ca²⁺ signaling in a manner similar to that of probiotics. Thus, ingestion of miso strengthened the immune response and tolerance in mice. These results appear to account, at least in part, to the salubrious effects of miso.

Intestinal commensal microbiota and cytokines regulate Fut2 ⁺ Paneth cells for gut defense
Mariko Kamioka, Yoshiyuki Goto, Kiminori Nakamura, Yuki Yokoi, Rina Sugimoto, Shuya Ohira, Yosuke Kurashima, Shingo Umemoto, Shintaro Sato, Jun Kunisawa, Yu Takahashi, Steven E. Domino, Jean-Christophe Renauld, Susumu Nakae, Yoichiro Iwakura, Peter B. Ernst, Tokiyoshi Ayabe, Hiroshi Kiyono
Proceedings of the National Academy of Sciences, 119, 3, Proceedings of the National Academy of Sciences, Jan. 2022, [Peer-reviewed], [International Magazine]
English, Scientific journal, Significance

Paneth cells produce granules containing antimicrobial peptides, such as α-defensin for host defense. Examination of the production and utilization of fucosyltransferase 2 (Fut2) by Paneth cells revealed two distinct subsets: Fut2 ⁺ Paneth cells and Fut2 ⁻ Paneth cells. Compared with Fut2 ⁻ Paneth cells, Fut2 ⁺ Paneth cells were enriched in granules containing antimicrobial peptides. IL-22 and IL-17a were found to be essential for commensal bacteria-dependent Fut2 ⁺ Paneth cell development and function as part of gut defense.

Lower human defensin 5 in elderly people compared to middle-aged is associated with differences in the intestinal microbiota composition: the DOSANCO Health Study.
Yu Shimizu, Kiminori Nakamura, Mani Kikuchi, Shigekazu Ukawa, Koshi Nakamura, Emiko Okada, Akihiro Imae, Takafumi Nakagawa, Ryodai Yamamura, Akiko Tamakoshi, Tokiyoshi Ayabe
GeroScience, 44, 2, 997, 1009, Springer Science and Business Media LLC, 08 Jun. 2021, [Peer-reviewed], [International Magazine]
English, Scientific journal, Recently, aging is considered a risk factor for various diseases. Although changes in the intestinal microbiota along with aging are thought to associate with the increased disease risk, mechanisms that cause age-related transition of the intestinal microbiota remain unknown. This study aims to clarify relationships between the amount of human defensin 5 (HD5), a Paneth cell α-defensin, which is known to regulate the intestinal microbiota, and age-related differences of the intestinal microbiota composition. Fecal samples from 196 healthy Japanese (35 to 81 years old) were collected and measured HD5 concentration. HD5 concentration in the elderly group (age > 70 years old) was significantly lower than the middle-aged group (age ≤ 70 years old). Furthermore, individual age was negatively correlated with HD5 concentration (r =  − 0.307, p < 0.001). In β-diversity, the intestinal microbiota of the elderly showed a significantly different composition compared to the middle-aged. At the genus level, relative abundance of Collinsella, Alistipes, Peptococcaceae; unassigned, Lactobacillus, Lactococcus, Weissella, Christensenellaceae R-7 group, Megasphaera, and [Eubacterium] eligens group was significantly higher, and Lachnospiraceae; unassigned, Blautia, Anaerostipes, Fusicatenibacter, Dorea, and Faecalibacterium was significantly lower in the elderly compared to the middle-aged. In addition, HD5 concentration was negatively correlated with Alistipes, Peptococcaceae; unassigned, and Christensenellaceae R-7 group and positively correlated with Lachnospiraceae; unassigned and Dorea. These results provide novel insights into the immunosenescence of enteric innate immunity, indicating low HD5 is suggested to contribute to the age-related differences in the intestinal microbiota and may relate to increased risk of diseases in elderly people.

Decrease of α-defensin impairs intestinal metabolite homeostasis via dysbiosis in mouse chronic social defeat stress model.
Kosuke Suzuki, Kiminori Nakamura, Yu Shimizu, Yuki Yokoi, Shuya Ohira, Mizu Hagiwara, Yi Wang, Yuchi Song, Tomoyasu Aizawa, Tokiyoshi Ayabe
Scientific reports, 11, 1, 9915, 9915, Springer Science and Business Media LLC, 10 May 2021, [Peer-reviewed], [International Magazine]
English, Scientific journal, Psychological stress has been reported to relate to dysbiosis, imbalance of the intestinal microbiota composition, and contribute to the onset and exacerbation of depression, though, underlying mechanisms of psychological stress-related dysbiosis have been unknown. It has been previously established that α-defensins, which are effector peptides of innate enteric immunity produced by Paneth cells in the small intestine, play an important role in regulation of the intestinal microbiota. However, the relationship between disruption of intestinal ecosystem and α-defensin under psychological stress is yet to be determined. Here we show using chronic social defeat stress (CSDS), a mouse depression model that (1) the exposure to CSDS significantly reduces α-defensin secretion by Paneth cells and (2) induces dysbiosis and significant composition changes in the intestinal metabolites. Furthermore, (3) they are recovered by administration of α-defensin. These results indicate that α-defensin plays an important role in maintaining homeostasis of the intestinal ecosystem under psychological stress, providing novel insights into the onset mechanism of stress-induced depression, and may further contribute to discovery of treatment targets for depression.

Simultaneous real-time analysis of Paneth cell and intestinal stem cell response to interferon-γ by a novel stem cell niche tracking method
Yuki Yokoi, Takahiro Adachi, Rina Sugimoto, Mani Kikuchi, Tokiyoshi Ayabe, Kiminori Nakamura
Biochemical and Biophysical Research Communications, 545, 14, 19, Elsevier BV, Mar. 2021, [Peer-reviewed]
Scientific journal

Mycotoxin Deoxynivalenol Has Different Impacts on Intestinal Barrier and Stem Cells by Its Route of Exposure
Hikaru Hanyu, Yuki Yokoi, Kiminori Nakamura, Tokiyoshi Ayabe, Keisuke Tanaka, Kinuko Uno, Katsuhiro Miyajima, Yuki Saito, Ken Iwatsuki, Makoto Shimizu, Miki Tadaishi, Kazuo Kobayashi-Hattori
Toxins, 12, 10, 610, 610, MDPI AG, 24 Sep. 2020, [Peer-reviewed]
Scientific journal, The different effects of deoxynivalenol (DON) on intestinal barrier and stem cells by its route of exposure remain less known. We explored the toxic effects of DON on intestinal barrier functions and stem cells after DON microinjection (luminal exposure) or addition to a culture medium (basolateral exposure) using three-dimensional mouse intestinal organoids (enteroids). The influx test using fluorescein-labeled dextran showed that basolateral DON exposure (1 micromolar (µM) disrupted intestinal barrier functions in enteroids compared with luminal DON exposure at the same concentration. Moreover, an immunofluorescence experiment of intestinal epithelial proteins, such as E-cadherin, claudin, zonula occludens-1 (ZO-1), and occludin, exhibited that only basolateral DON exposure broke down intestinal epithelial integrity. A time-lapse analysis using enteroids from leucine-rich repeat-containing G-protein-coupled receptor 5 (Lgr5)-enhanced green fluorescence protein (EGFP) transgenic mice and 5-ethynyl-2-deoxyuridine (EdU) assay indicated that only the basolateral DON exposure, but not luminal DON exposure, suppressed Lgr5+ stem cell count and proliferative cell ratio, respectively. These results revealed that basolateral DON exposure has larger impacts on intestinal barrier function and stem cells than luminal DON exposure. This is the first report that DON had different impacts on intestinal stem cells depending on the administration route. In addition, RNA sequencing analysis showed different expression of genes among enteroids after basolateral and luminal DON exposure.

Paneth cell α-defensin misfolding correlates with dysbiosis and ileitis in Crohn's disease model mice.
Yu Shimizu, Kiminori Nakamura, Aki Yoshii, Yuki Yokoi, Mani Kikuchi, Ryuga Shinozaki, Shunta Nakamura, Shuya Ohira, Rina Sugimoto, Tokiyoshi Ayabe
Life science alliance, 3, 6, e201900592, e201900592, Life Science Alliance, LLC, Jun. 2020, [Peer-reviewed], [International Magazine]
English, Scientific journal, Crohn’s disease (CD) is an intractable inflammatory bowel disease, and dysbiosis, disruption of the intestinal microbiota, is associated with CD pathophysiology. ER stress, disruption of ER homeostasis in Paneth cells of the small intestine, and α-defensin misfolding have been reported in CD patients. Because α-defensins regulate the composition of the intestinal microbiota, their misfolding may cause dysbiosis. However, whether ER stress, α-defensin misfolding, and dysbiosis contribute to the pathophysiology of CD remains unknown. Here, we show that abnormal Paneth cells with markers of ER stress appear in SAMP1/YitFc, a mouse model of CD, along with disease progression. Those mice secrete reduced-form α-defensins that lack disulfide bonds into the intestinal lumen, a condition not found in normal mice, and reduced-form α-defensins correlate with dysbiosis during disease progression. Moreover, administration of reduced-form α-defensins to wild-type mice induces the dysbiosis. These data provide novel insights into CD pathogenesis induced by dysbiosis resulting from Paneth cell α-defensin misfolding and they suggest further that Paneth cells may be potential therapeutic targets.

Disease progression-associated alterations in fecal metabolites in SAMP1/YitFc mice, a Crohn's disease model.
Yosuke Komatsu, Yu Shimizu, Megumi Yamano, Mani Kikuchi, Kiminori Nakamura, Tokiyoshi Ayabe, Tomoyasu Aizawa
Metabolomics., 16, 4, 48, 48, Springer Science and Business Media {LLC}, 10 Apr. 2020, [Peer-reviewed], [International Magazine]
English, Scientific journal, INTRODUCTION: Crohn's disease (CD) is a chronic, relapsing inflammatory bowel disease affecting the gastrointestinal tract. Although its precise etiology has not been fully elucidated, an imbalance of the intestinal microbiota has been known to play a role in CD. Fecal metabolites derived from microbiota may be related to the onset and progression of CD OBJECTIVES: This study aimed to clarify the transition of gut microbiota and fecal metabolites associated with disease progression using SAMP1/YitFc mice, a model of spontaneous CD METHODS: The ileum tissues isolated from SAMP1/YitFc mice at different ages were stained with hematoxylin-eosin for histologic characterization with CD progression. Feces from control, Institute of Cancer Research (ICR; n = 6), and SAMP1/YitFc (n = 8) mice at different ages were subjected to microbial analysis and 1H nuclear magnetic resonance (NMR) analysis to investigate fluctuations in gut microbiota and fecal metabolites with CD progression RESULTS: Relative abundance of the Lachnospiraceae, Ruminococcaceae, Bacteroidaceae, and Bacteroidales S24-7 at family-level gut microbiota and fecal metabolites, such as short-chain fatty acids, lactate, glucose, xylose, and choline, dramatically fluctuated with histologic progression of intestinal inflammation in SAMP1/YitFc mice. Unlike the other metabolites, fecal taurine concentration in SAMP1/YitFc mice was higher than ICR mice regardless of age CONCLUSION: The fecal metabolites showing characteristic fluctuations may help to understand the inflammatory mechanism associated with CD, and might be utilized as potential biomarkers in predicting CD pathology.

Analysis of Serotonin in Human Feces Using Solid Phase Extraction and Column-Switching LC-MS/MS.
Yukiko Hirabayashi, Kiminori Nakamura, Tsuyoshi Sonehara, Daisuke Suzuki, Satoru Hanzawa, Yu Shimizu, Tomoyasu Aizawa, Koshi Nakamura, Akiko Tamakoshi, Tokiyoshi Ayabe
Mass spectrometry (Tokyo)., 9, 1, A0081, 2020, [Peer-reviewed], [Domestic magazines]
English, Scientific journal, Serotonin, an important neurotransmitter, is produced mainly in intestines, and serotonin levels in feces can be an indicator of the intestinal environment. Human feces, however, contain a large amount of contaminants, which vary widely owing to food contents and the intestinal environment, and these contaminants would be expected to interfere with the determination of serotonin levels in human feces. To remove these contaminants and determine serotonin levels, we developed a new method using solid phase extraction (SPE) and column-switching LC-MS/MS. Serotonin, labeled with a stable isotope, was added to human feces samples prior to SPE as an internal standard to correct for individual differences in matrix effects. The recovery rate for SPE was 55.9-81.0% (intraday) and 56.5-78.1% (interday) for feces from two subjects. We analyzed 220 fecal samples from 96 subjects including 76 pregnant and post-delivery women. The endogenous serotonin content per unit weight of dried feces was 0.09-14.13 ng/mg for pregnant and post-delivery women and 0.30-9.93 ng/mg for the remaining subjects.

Expression and Localization of Paneth Cells and Their α-Defensins in the Small Intestine of Adult Mouse.
Kiminori Nakamura, Yuki Yokoi, Rie Fukaya, Shuya Ohira, Ryuga Shinozaki, Takuto Nishida, Mani Kikuchi, Tokiyoshi Ayabe
Frontiers in immunology, 11, 570296, 570296, 2020, [Peer-reviewed], [International Magazine]
English, Scientific journal, Paneth cells contribute to intestinal innate immunity by sensing bacteria and secreting α-defensin. In Institute of Cancer Research (ICR) mice, α-defensin termed cryptdin (Crp) in Paneth cells consists of six major isoforms, Crp1 to 6. Despite accumulating evidences that α-defensin functions in controlling the intestinal microbiota, topographical localization of Paneth cells in the small intestine in relation to functions of α-defensin remains to be determined. In this study, we examined the expression level of messenger RNA (mRNA) encoding six Crp-isoforms and Crp immunoreactivities using singly isolated crypts together with bactericidal activities of Paneth cell secretions from isolated crypts of duodenum, jejunum, and ileum. Here we showed that levels of Crp mRNAs in the single crypt ranged from 5 x 103 to 1 x 106 copies per 5 ng RNA. For each Crp isoform, the expression level in ileum was 4 to 50 times higher than that in duodenum and jejunum. Furthermore, immunohistochemical analysis of isolated crypts revealed that the average number of Paneth cell per crypt in the small intestine increased from proximal to distal, three to seven-fold, respectively. Both Crp1 and 4 expressed greater in ileal Paneth cells than those in duodenum or jejunum. Bactericidal activities in secretions of ileal Paneth cell exposed to bacteria were significantly higher than those of duodenum or jejunum. In germ-free mice, Crp expression in each site of the small intestine was attenuated and bactericidal activities released by ileal Paneth cells were decreased compared to those in conventional mice. Taken together, Paneth cells and their α-defensin in adult mouse appeared to be regulated topographically in innate immunity to control intestinal integrity.

Associations of gut microbiota, dietary intake, and serum short-chain fatty acids with fecal short-chain fatty acids.
Ryodai YAMAMURA, Koshi NAKAMURA, Naoya KITADA, Tomoyasu AIZAWA, Yu SHIMIZU, Kiminori NAKAMURA, Tokiyoshi AYABE, Takashi KIMURA, Akiko TAMAKOSHI
Bioscience of Microbiota, Food and Health, 39, 1, 11, 17, BMFH Press, 2020, [Peer-reviewed]
Scientific journal

Butyric Acid and Leucine Induce α-Defensin Secretion from Small Intestinal Paneth Cells.
Akiko Takakuwa, Kiminori Nakamura, Mani Kikuchi, Rina Sugimoto, Shuya Ohira, Yuki Yokoi, Tokiyoshi Ayabe
Nutrients, 11, 11, 18 Nov. 2019, [Peer-reviewed], [International Magazine]
English, Scientific journal, The intestine not only plays a role in fundamental processes in digestion and nutrient absorption, but it also has a role in eliminating ingested pathogenic bacteria and viruses. Paneth cells, which reside at the base of small intestinal crypts, secrete α-defensins and contribute to enteric innate immunity through potent microbicidal activities. However, the relationship between food factors and the innate immune functions of Paneth cells remains unknown. Here, we examined whether short-chain fatty acids and amino acids induce α-defensin secretion from Paneth cells in the isolated crypts of small intestine. Butyric acid and leucine elicit α-defensin secretion by Paneth cells, which kills Salmonella typhimurium. We further measured Paneth cell secretion in response to butyric acid and leucine using enteroids, a three-dimensional ex vivo culture system of small intestinal epithelial cells. Paneth cells expressed short-chain fatty acid receptors, Gpr41, Gpr43, and Gpr109a mRNAs for butyric acid, and amino acid transporter Slc7a8 mRNA for leucine. Antagonists of Gpr41 and Slc7a8 inhibited granule secretion by Paneth cells, indicating that these receptor and transporter on Paneth cells induce granule secretion. Our findings suggest that Paneth cells may contribute to intestinal homeostasis by secreting α-defensins in response to certain nutrients or metabolites.

A simple culture method for liver and intestinal tissue-resident macrophages from neonatal mice.
Yu Shimizu, Naoya Sakuragi, Kiminori Nakamura, Toshio Taira, Tokiyoshi Ayabe, Akimasa Fukui
In vitro cellular & developmental biology. Animal, 55, 6, 436, 444, Jun. 2019, [Peer-reviewed], [International Magazine]
English, Scientific journal, The liver and intestine contain a remarkably large portion of tissue-resident macrophage cells representing a phenotype that downregulates inflammation and initiates tissue repair. Here, liver and intestinal tissues obtained from neonatal mice were minced, enzymatically digested, and incubated in RPMI1640-based media. In a 2-wk culture, spherical floating cells emerged on a fibroblastic sheet. These cells showed phagocytic activity and F4/80+-CD11b+-CD206+-Arg1+-iNOS--CD209a- phenotype, suggesting that these cells are tissue-resident macrophages. These macrophages proliferated in the co-culture system in the presence of fibroblastic feeder cell layer and absence of supplemental cytokines; the co-culture system did not cause a significant change in the phenotype of cells grown in a 4-wk culture. On the feeder cells, macrophage density was approximately 1.5 × 104/cm2 and the doubling time was approximately 70 h. Based on these observations, we present a simple method for the isolation and propagation of tissue-resident macrophages resembling M2 macrophage from neonatal mice, and this method provides a useful platform for in vitro studies of tissue-resident macrophages.

Paneth cell granule dynamics on secretory responses to bacterial stimuli in enteroids.
Yuki Yokoi, Kiminori Nakamura, Tsukasa Yoneda, Mani Kikuchi, Rina Sugimoto, Yu Shimizu, Tokiyoshi Ayabe
Scientific reports, 9, 1, 2710, 2710, 25 Feb. 2019, [Peer-reviewed], [International Magazine]
English, Scientific journal, Paneth cells at the base of small intestinal crypts secrete granules containing α-defensins in response to bacteria and maintain the intestinal environment by clearing enteric pathogens and regulating the composition of the intestinal microbiota. However, Paneth cell secretory responses remain debatable and the mechanisms that regulate the secretion are not well understood. Although enteroids, three-dimensional cultures of small intestinal epithelial cells, have proven useful for analyzing intestinal epithelial cell functions including ion transport, their closed structures have imposed limitations to investigating interactions between Paneth cells and the intestinal microbiota. Here, we report that microinjection of bacteria or lipopolysaccharide (LPS) into the enteroid lumen provides an ex vivo system for studying Paneth cell secretion in real-time. The results show that Paneth cells released granules immediately when the apical surfaces of enteroid epithelial cells were exposed to LPS or live bacteria by microinjection. However, Paneth cells did not respond to LPS delivered in culture media to enteroid exterior basolateral surface, although they responded to basolateral carbamyl choline. In addition, Paneth cells replenished their granules after secretion, enabling responses to second stimulation. These findings provide new insight for apically-induced Paneth cell secretory responses in regulating the intestinal environment.

Myc-induced nuclear antigen constrains a latent intestinal epithelial cell-intrinsic anthelmintic pathway.
Meenu R Pillai, Belgacem Mihi, Kenji Ishiwata, Kiminori Nakamura, Naoya Sakuragi, David B Finkelstein, Maureen A McGargill, Toshinori Nakayama, Tokiyoshi Ayabe, Mathew L Coleman, Mark Bix
PloS one, 14, 2, e0211244, Feb. 2019, [Peer-reviewed], [International Magazine]
English, Scientific journal, Expulsion of parasitic gastrointestinal nematodes requires diverse effector mechanisms coordinated by a Th2-type response. The evolutionarily conserved JmjC protein; Myc Induced Nuclear Antigen (Mina) has been shown to repress IL4, a key Th2 cytokine, suggesting Mina may negatively regulate nematode expulsion. Here we report that expulsion of the parasitic nematode Trichuris muris was indeed accelerated in Mina deficient mice. Unexpectedly, this was associated not with an elevated Th2- but rather an impaired Th1-type response. Further reciprocal bone marrow chimera and conditional KO experiments demonstrated that retarded parasite expulsion and a normal Th1-type response both required Mina in intestinal epithelial cells (IECs). Transcriptional profiling experiments in IECs revealed anti-microbial α-defensin peptides to be the major target of Mina-dependent retention of worms in infected mice. In vitro exposure to recombinant α-defensin peptides caused cytotoxic damage to whipworms. These results identify a latent IEC-intrinsic anthelmintic pathway actively constrained by Mina and point to α-defensins as important effectors that together with Mina may be attractive therapeutic targets for the control of nematode infection.

Bifidogenic and butyrogenic effects of young barely leaf extract in an in vitro human colonic microbiota model
Daisuke Sasaki, Kengo Sasaki, Yasushi Kadowaki, Yasuyuki Aotsuka, Akihiko Kondo
AMB Express, 9, 1, 2019
English, Scientific journal

Correction: Entamoeba histolytica alters ileal paneth cell functions in intact and Muc2 Mucin deficiency (Infection and Immunity (2018) 86:7 (e00208-18) DOI: 10.1128/IAI.00208-18)
Eduardo R. Cobo, Ravi Holani, France Moreau, Kiminori Nakamura, Tokiyoshi Ayabe, Jennifer R. Mastroianni, Yoshihiro Eriguchi, Andre Ouellette, Kris Chadee
Infection and Immunity, 86, 10, American Society for Microbiology, 01 Oct. 2018
English, Scientific journal

Essential role of IFN-γ in T cell–associated intestinal inflammation.
Yoshihiro Eriguchi, Kiminori Nakamura, Yuki Yokoi, Rina Sugimoto, Shuichiro Takahashi, Daigo Hashimoto, Takanori Teshima, Tokiyoshi Ayabe, Michael E. Selsted, André J. Ouellette
JCI Insight, 3, 18, 20 Sep. 2018, [Peer-reviewed]
Scientific journal

Ploidy-dependent change in cyclin D2 expression and sensitization to cdk4/6 inhibition in human somatic haploid cells
Kan Yaguchi, Takahiro Yamamoto, Masaya Shimada, Rina Sugimoto, Kiminori Nakamura, Tokiyoshi Ayabe, Ryota Uehara
Biochemical and Biophysical Research Communications, 504, 1, 231, 237, Elsevier BV, Sep. 2018, [Peer-reviewed], [International Magazine]
English, Scientific journal, Near-haploidy is observed in certain cancer types, but ploidy-dependent alterations in gene regulation in the haploid state remain elusive. Here, by comparative transcriptome analysis between human isogenic haploid and diploid cell lines, we found lowering of cyclin D2 level in haploids. Acute genome duplication in haploids restored cyclin D2 expression to diploid level, indicating that the regulation of cyclin D2 expression is directly linked to ploidy. Downstream pathways of cyclin D2, such as Rb phosphorylation and p27 sequestration remained intact in haploids, suggesting that they adapt to lowered cyclin D level. Interestingly, however, haploid cells were more susceptible to cdk4/6 inhibition compared to diploids. Our finding indicates feasibility of selective growth suppression of haploid cells based on ploidy-linked gene regulation.

Entamoeba histolytica Alters Ileal Paneth Cell Functions in Intact and Muc2 Mucin Deficiency.
Eduardo R Cobo, Ravi Holani, France Moreau, Kiminori Nakamura, Tokiyoshi Ayabe, Jennifer R Mastroianni, Yoshihiro Eriguchi, Andre Ouellette, Kris Chadee
Infection and immunity, 86, 7, e00208, 18, Jul. 2018, [Peer-reviewed], [International Magazine]
English, Scientific journal, Enteric α-defensins, termed cryptdins (Crps) in mice, and lysozymes secreted by Paneth cells contribute to innate host defense in the ileum. Antimicrobial factors, including lysozymes and β-defensins, are often embedded in luminal glycosylated colonic Muc2 mucin secreted by goblet cells that form the protective mucus layer critical for gut homeostasis and pathogen invasion. In this study, we investigated ileal innate immunity against Entamoeba histolytica, the causative agent of intestinal amebiasis, by inoculating parasites in closed ileal loops in Muc2+/+ and Muc2-/- littermates and quantifying Paneth cell localization (lysozyme expression) and function (Crp secretion). Relative to Muc2+/+ littermates, Muc2-/- littermates showed a disorganized mislocalization of Paneth cells that was diffusely distributed, with elevated lysozyme secretion in the crypts and on villi in response to E. histolytica Inhibition of E. histolytica Gal/GalNAc lectin (Gal-lectin) binding with exogenous galactose and Entamoeba histolytica cysteine proteinase 5 (EhCP5)-negative E. histolytica had no effect on parasite-induced erratic Paneth cell lysozyme synthesis. Although the basal ileal expression of Crp genes was unaffected in Muc2-/- mice in response to E. histolytica, there was a robust release of proinflammatory cytokines and Crp peptide secretions in luminal exudates that was also present in the colon. Interestingly, E. histolytica-secreted cysteine proteinases cleaved the proregion of Crp4 but not the active form. These findings define Muc2 mucin as an essential component of ileal barrier function that regulates the localization and function of Paneth cells critical for host defense against microbes.

R-Spondin1 expands Paneth cells and prevents dysbiosis induced by graft-versus-host disease.
Eiko Hayase, Daigo Hashimoto, Kiminori Nakamura, Clara Noizat, Reiki Ogasawara, Shuichiro Takahashi, Hiroyuki Ohigashi, Yuki Yokoi, Rina Sugimoto, Satomi Matsuoka, Takahide Ara, Emi Yokoyama, Tomohiro Yamakawa, Ko Ebata, Takeshi Kondo, Rina Hiramine, Tomoyasu Aizawa, Yoshitoshi Ogura, Tetsuya Hayashi, Hiroshi Mori, Ken Kurokawa, Kazuma Tomizuka, Tokiyoshi Ayabe, Takanori Teshima
The Journal of experimental medicine, 214, 12, 3507, 3518, 04 Dec. 2017, [Peer-reviewed], [International Magazine]
English, Scientific journal

Paneth cell α-defensins and enteric microbiota in health and disease.
Kiminori NAKAMURA, Naoya SAKURAGI, Akiko TAKAKUWA, Tokiyoshi AYABE
Bioscience of Microbiota, Food and Health, 35, 2, 57, 67, 2016, [Peer-reviewed]
Scientific journal

Decreased secretion of Paneth cell -defensins in graft-versus-host disease
Y. Eriguchi, K. Nakamura, D. Hashimoto, S. Shimoda, N. Shimono, K. Akashi, T. Ayabe, T. Teshima
TRANSPLANT INFECTIOUS DISEASE, 17, 5, 702, 706, Oct. 2015, [Peer-reviewed]
English, Scientific journal

Stiff substrates increase YAP-signaling-mediated matrix metalloproteinase-7 expression
A Nukuda, C Sasaki, S Ishihara, T Mizutani, K Nakamura, T Ayabe, K Kawabata, H Haga
Oncogenesis, 4, 9, e165, e165, Sep. 2015, [Peer-reviewed]
English, Scientific journal

Efficient production of a correctly folded mouse α-defensin, cryptdin-4, by refolding during inclusion body solubilization.
Satoshi Tomisawa, Yuji Sato, Masakatsu Kamiya, Yasuhiro Kumaki, Takashi Kikukawa, Keiichi Kawano, Makoto Demura, Kiminori Nakamura, Tokiyoshi Ayabe, Tomoyasu Aizawa
Protein expression and purification, 112, 21, 8, Aug. 2015, [Peer-reviewed], [International Magazine]
English, Scientific journal

Pr1E11, a novel anti-TROP-2 antibody isolated by adenovirus-based antibody screening, recognizes a unique epitope.
Masahiro Ikeda, Miki Yamaguchi, Kazunori Kato, Kiminori Nakamura, Sagano Shiina, Takako Ichikawa-Ando, Hirofumi Misaka, Kensuke Myojo, Kazuyasu Nakamura, Yoshiyuki Sugimoto, Hirofumi Hamada
Biochemical and biophysical research communications, 458, 4, 877, 82, 20 Mar. 2015, [Peer-reviewed], [International Magazine]
English, Scientific journal

Bacterial cell wall components regulate adipokine secretion from visceral adipocytes.
Risa Taira, Sayori Yamaguchi, Kyoko Shimizu, Kiminori Nakamura, Tokiyoshi Ayabe, Toshio Taira
Journal of clinical biochemistry and nutrition, 56, 2, 149, 54, Mar. 2015, [Peer-reviewed], [Domestic magazines]
English, Scientific journal

Development of a sensitive screening method for selecting monoclonal antibodies to be internalized by cells.
Miki Yamaguchi, Yukari Nishii, Kiminori Nakamura, Haruka Aoki, Sachie Hirai, Hiroaki Uchida, Yuji Sakuma, Hirofumi Hamada
Biochemical and biophysical research communications, 454, 4, 600, 3, 28 Nov. 2014, [Peer-reviewed], [International Magazine]
English, Scientific journal

A monoclonal antibody-based sandwich enzyme-linked immunosorbent assay for detection of secreted α-defensin.
Kiminori Nakamura, Naoya Sakuragi, Tokiyoshi Ayabe
Analytical biochemistry, 443, 2, 124, 31, 2, 15 Dec. 2013, [Peer-reviewed], [International Magazine]
English, Scientific journal

Reciprocal expression of enteric antimicrobial proteins in intestinal graft-versus-host disease.
Yoshihiro Eriguchi, Hidetaka Uryu, Kiminori Nakamura, Sonoko Shimoji, Shuichiro Takashima, Hiromi Iwasaki, Toshihiro Miyamoto, Nobuyuki Shimono, Daigo Hashimoto, Koichi Akashi, Tokiyoshi Ayabe, Takanori Teshima
Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation, 19, 10, 1525, 9, Oct. 2013, [Peer-reviewed], [International Magazine]
English, Scientific journal

Molecular Mechanisms of the Cytotoxicity of Human alpha-Lactalbumin Made Lethal to Tumor Cells (HAMLET) and Other Protein-Oleic Acid Complexes
Takashi Nakamura, Tomoyasu Aizawa, Ryusho Kariya, Seiji Okada, Makoto Demura, Keiichi Kawano, Koki Makabe, Kunihiro Kuwajima
JOURNAL OF BIOLOGICAL CHEMISTRY, 288, 20, 14408, 14416, May 2013, [Peer-reviewed]
English, Scientific journal

Intracellular superoxide dismutase activity defines invasiveness of the murine T-lymphoma cell line L5187Y-ML25 in vitro and in vivo.
Maki Tanaka, Kageaki Kuribayashi, Kastuhisa Kogawa, Kiminori Nakamura, Naoki Watanabe
Leukemia research, 37, 1, 89, 92, 1, Jan. 2013, [Peer-reviewed], [International Magazine]
English, Scientific journal

Therapeutic effect of suicide gene-transferred mesenchymal stem cells in a rat model of glioma
H. Kosaka, T. Ichikawa, K. Kurozumi, H. Kambara, S. Inoue, T. Maruo, K. Nakamura, H. Hamada, I. Date
CANCER GENE THERAPY, 19, 8, 572, 578, Aug. 2012, [Peer-reviewed]
English, Scientific journal

Graft-versus-host disease disrupts intestinal microbial ecology by inhibiting Paneth cell production of α-defensins.
Yoshihiro Eriguchi, Shuichiro Takashima, Hideyo Oka, Sonoko Shimoji, Kiminori Nakamura, Hidetaka Uryu, Shinji Shimoda, Hiromi Iwasaki, Nobuyuki Shimono, Tokiyoshi Ayabe, Koichi Akashi, Takanori Teshima
Blood, 120, 1, 223, 31, 05 Jul. 2012, [Peer-reviewed], [International Magazine]
English, Scientific journal

Paneth cells and stem cells in the intestinal stem cell niche and their association with inflammatory bowel disease.
Nakamura K, Ayabe T
Inflammation Regeneration., 32, 2, 53, 60, 2012, [Peer-reviewed]
Scientific journal

EpCAM- and EGFR-targeted selective gene therapy for biliary cancers using Z33-fiber-modified adenovirus.
Rei Kawashima, Masato Abei, Kuniaki Fukuda, Kiminori Nakamura, Takehide Murata, Mariko Wakayama, Emiko Seo, Naoyuki Hasegawa, Hiroyuki Mizuguchi, Yuichi Obata, Ichinosuke Hyodo, Hirofumi Hamada, Kazunari K Yokoyama
International journal of cancer, 129, 5, 1244, 53, 01 Sep. 2011, [Peer-reviewed], [International Magazine]
English, Scientific journal

Neural cell adhesion molecule 2 as a target molecule for prostate and breast cancer gene therapy.
Shu Takahashi, Kazunori Kato, Kiminori Nakamura, Rika Nakano, Kazuishi Kubota, Hirofumi Hamada
Cancer science, 102, 4, 808, 14, Apr. 2011, [Peer-reviewed], [International Magazine]
English, Scientific journal

Bactericidal activity of mouse α-defensin cryptdin-4 predominantly affects noncommensal bacteria.
Koji Masuda, Naoki Sakai, Kiminori Nakamura, Sawako Yoshioka, Tokiyoshi Ayabe
Journal of innate immunity, 3, 3, 315, 26, 2011, [Peer-reviewed], [International Magazine]
English, Scientific journal

Regulation of Microbiota by Antimicrobial Peptides in the Gut.
Koji Masuda, Kiminori Nakamura, Sawako Yoshioka, Rie Fukaya, Naoki Sakai, Tokiyoshi Ayabe
Recent Advances in Tonsils and Mucosal Barriers of the Upper Airways, 72, 97, 99, 2011, [Peer-reviewed], [International Magazine]
English, In book

Interleukin-2 gene transfer potentiates the alpha-galactosylceramide-stimulated antitumor effect by the induction of TRAIL in NKT and NK cells in mouse models of subcutaneous and metastatic carcinoma.
Yoshiki Nishihori, Kazunori Kato, Maki Tanaka, Tetsuro Okamoto, Seiya Hagiwara, Naoko Araki, Katsuhisa Kogawa, Kageaki Kuribayashi, Kiminori Nakamura, Yoshiro Niitsu
Cancer biology & therapy, 8, 18, 1763, 70, Sep. 2009, [Peer-reviewed], [International Magazine]
English, Scientific journal

Emerging concepts in biomarker discovery; the US-Japan Workshop on Immunological Molecular Markers in Oncology.
Hideaki Tahara, Marimo Sato, Magdalena Thurin, Ena Wang, Lisa H Butterfield, Mary L Disis, Bernard A Fox, Peter P Lee, Samir N Khleif, Jon M Wigginton, Stefan Ambs, Yasunori Akutsu, Damien Chaussabel, Yuichiro Doki, Oleg Eremin, Wolf Hervé Fridman, Yoshihiko Hirohashi, Kohzoh Imai, James Jacobson, Masahisa Jinushi, Akira Kanamoto, Mohammed Kashani-Sabet, Kazunori Kato, Yutaka Kawakami, John M Kirkwood, Thomas O Kleen, Paul V Lehmann, Lance Liotta, Michael T Lotze, Michele Maio, Anatoli Malyguine, Giuseppe Masucci, Hisahiro Matsubara, Shawmarie Mayrand-Chung, Kiminori Nakamura, Hiroyoshi Nishikawa, A Karolina Palucka, Emanuel F Petricoin, Zoltan Pos, Antoni Ribas, Licia Rivoltini, Noriyuki Sato, Hiroshi Shiku, Craig L Slingluff, Howard Streicher, David F Stroncek, Hiroya Takeuchi, Minoru Toyota, Hisashi Wada, Xifeng Wu, Julia Wulfkuhle, Tomonori Yaguchi, Benjamin Zeskind, Yingdong Zhao, Mai-Britt Zocca, Francesco M Marincola
Journal of translational medicine, 7, 45, 45, 17 Jun. 2009, [International Magazine]
English, Supported by the Office of International Affairs, National Cancer Institute (NCI), the "US-Japan Workshop on Immunological Biomarkers in Oncology" was held in March 2009. The workshop was related to a task force launched by the International Society for the Biological Therapy of Cancer (iSBTc) and the United States Food and Drug Administration (FDA) to identify strategies for biomarker discovery and validation in the field of biotherapy. The effort will culminate on October 28th 2009 in the "iSBTc-FDA-NCI Workshop on Prognostic and Predictive Immunologic Biomarkers in Cancer", which will be held in Washington DC in association with the Annual Meeting. The purposes of the US-Japan workshop were a) to discuss novel approaches to enhance the discovery of predictive and/or prognostic markers in cancer immunotherapy; b) to define the state of the science in biomarker discovery and validation. The participation of Japanese and US scientists provided the opportunity to identify shared or discordant themes across the distinct immune genetic background and the diverse prevalence of disease between the two Nations. Converging concepts were identified: enhanced knowledge of interferon-related pathways was found to be central to the understanding of immune-mediated tissue-specific destruction (TSD) of which tumor rejection is a representative facet. Although the expression of interferon-stimulated genes (ISGs) likely mediates the inflammatory process leading to tumor rejection, it is insufficient by itself and the associated mechanisms need to be identified. It is likely that adaptive immune responses play a broader role in tumor rejection than those strictly related to their antigen-specificity; likely, their primary role is to trigger an acute and tissue-specific inflammatory response at the tumor site that leads to rejection upon recruitment of additional innate and adaptive immune mechanisms. Other candidate systemic and/or tissue-specific biomarkers were recognized that might be added to the list of known entities applicable in immunotherapy trials. The need for a systematic approach to biomarker discovery that takes advantage of powerful high-throughput technologies was recognized; it was clear from the current state of the science that immunotherapy is still in a discovery phase and only a few of the current biomarkers warrant extensive validation. It was, finally, clear that, while current technologies have almost limitless potential, inadequate study design, limited standardization and cross-validation among laboratories and suboptimal comparability of data remain major road blocks. The institution of an interactive consortium for high throughput molecular monitoring of clinical trials with voluntary participation might provide cost-effective solutions.

Effect of transplantation of bone marrow-derived mesenchymal stem cells on mice infected with prions.
Chang-Hyun Song, Osamu Honmou, Natsuo Ohsawa, Kiminori Nakamura, Hirofumi Hamada, Hidefumi Furuoka, Rie Hasebe, Motohiro Horiuchi
Journal of virology, 83, 11, 5918, 27, Jun. 2009, [Peer-reviewed], [International Magazine]
English, Scientific journal

Targeting vectors for cancer gene therapy.
Kiminori Nakamura, Kazunori Kato, Toshihiro Tanaka, Hirofumi Hamada
Frontiers in bioscience (Elite edition), 1, 1, 332, 40, 01 Jun. 2009, [Peer-reviewed], [International Magazine]
English, Scientific journal

Selective gene transfer into neurons via Na,K-ATPase beta1. Targeting gene transfer with monoclonal antibody and adenovirus vector.
Keiji Ishii, Kiminori Nakamura, Satoshi Kawaguchi, Rong Li, Sachie Hirai, Naoya Sakuragi, Takuro Wada, Kazunori Kato, Toshihiko Yamashita, Hirofumi Hamada
The journal of gene medicine, 10, 6, 597, 609, Jun. 2008, [Peer-reviewed], [International Magazine]
English, Scientific journal

Gene transfer of CD40-ligand to dendritic cells stimulates interferon-gamma production to induce growth arrest and apoptosis of tumor cells.
K. Tomihara, K. Kato, Y. Masuta, K. Nakamura, H. Uchida, K. Sasaki, T. Tanaka, J. Huang, H. Hiratsuka, H. Hamada
GENE THERAPY, 15, 3, 203, 213, Feb. 2008, [Peer-reviewed]
English, Scientific journal

Gene transfer of noncleavable cell surface mutants of human CD154 induces the immune response and diminishes systemic inflammatory reactions.
Yukari Masuta, Kazunori Kato, Kei Tomihara, Kiminori Nakamura, Katsunori Sasaki, Satoshi Takahashi, Hirofumi Hamada
Journal of immunotherapy, 30, 7, 694, 704, Oct. 2007, [Peer-reviewed], [International Magazine]
English, Scientific journal

Exploration of target molecules for prostate cancer gene therapy.
Kazuhiro Suzuki, Kiminori Nakamura, Kazunori Kato, Hirofumi Hamada, Taiji Tsukamoto
The Prostate, 67, 11, 1163, 73, 01 Aug. 2007, [Peer-reviewed], [International Magazine]
English, Scientific journal

Wnt3/RhoA/ROCK signaling pathway is involved in adhesion-mediated drug resistance of multiple myeloma in an autocrine mechanism.
Masayoshi Kobune, Hiroki Chiba, Junji Kato, Kazunori Kato, Kiminori Nakamura, Yutaka Kawano, Kohichi Takada, Rishu Takimoto, Tetsuji Takayama, Hirofumi Hamada, Yoshiro Niitsu
Molecular cancer therapeutics, 6, 6, 1774, 84, Jun. 2007, [Peer-reviewed], [International Magazine]
English, Scientific journal

Gene transfer of the CD40-ligand to human dendritic cells induces NK-mediated antitumor effects against human carcinoma cells.
Kei Tomihara, Kazunori Kato, Yukari Masuta, Kiminori Nakamura, Toshihiro Tanaka, Hiroyoshi Hiratsuka, Hirofumi Hamada
International journal of cancer, 120, 7, 1491, 8, 01 Apr. 2007, [Peer-reviewed], [International Magazine]
English, Scientific journal

Essential role of protein kinase C zeta in transducing a motility signal induced by superoxide and a chemotactic peptide, fMLP.
Kageaki Kuribayashi, Kiminori Nakamura, Maki Tanaka, Tsutomu Sato, Junji Kato, Katsunori Sasaki, Rishu Takimoto, Katsuhisa Kogawa, Takeshi Terui, Tetsuji Takayama, Takayuki Onuma, Takuya Matsunaga, Yoshiro Niitsu
The Journal of cell biology, 176, 7, 1049, 60, 26 Mar. 2007, [Peer-reviewed], [International Magazine]
English, Scientific journal

Neuroprotection by PlGF gene-modified human mesenchymal stem cells after cerebral ischaemia.
H. Liu, O. Honmou, K. Harada, K. Nakamura, K. Houkin, H. Hamada, J. D. Kocsis
BRAIN, 129, 2734, 2745, Oct. 2006, [Peer-reviewed]
English, Scientific journal

Ex vivo expansion of G-CSF-mobilized peripheral blood CD133+ progenitor cells on coculture with human stromal cells.
Yutaka Kawano, Masayoshi Kobune, Hiroki Chiba, Kiminori Nakamura, Rishu Takimoto, Kohichi Takada, Yoshinori Ito, Junji Kato, Hirofumi Hamada, Yoshiro Niitsu
Experimental hematology, 34, 2, 150, 8, Feb. 2006, [Peer-reviewed], [International Magazine]
English, Scientific journal

Human mesenchymal stem cells xenografted directly to rat liver are differentiated into human hepatocytes without fusion.
Yasushi Sato, Hironobu Araki, Junji Kato, Kiminori Nakamura, Yutaka Kawano, Masayoshi Kobune, Tsutomu Sato, Koji Miyanishi, Tetsuji Takayama, Minoru Takahashi, Rishu Takimoto, Satoshi Iyama, Takuya Matsunaga, Seiji Ohtani, Akihiro Matsuura, Hirofumi Hamada, Yoshiro Niitsu
Blood, 106, 2, 756, 63, 15 Jul. 2005, [Peer-reviewed], [International Magazine]
English, Scientific journal

Bcl-xL gene transfer inhibits Bax translocation and prolongs cardiac cold preservation time in rats.
Jianhua Huang, Kiminori Nakamura, Yoshinori Ito, Takeshi Uzuka, Masayuki Morikawa, Sachie Hirai, Kei Tomihara, Toshihiro Tanaka, Yukari Masuta, Keiji Ishii, Kazunori Kato, Hirofumi Hamada
Circulation, 112, 1, 76, 83, 05 Jul. 2005, [Peer-reviewed], [International Magazine]
English, Scientific journal

Mesenchymal stem cells (MSC) as therapeutic cytoreagents for gene therapy.
Hirofumi Hamada, Masayoshi Kobune, Kiminori Nakamura, Yutaka Kawano, Kazunori Kato, Osamu Honmou, Kiyohiro Houkin, Takuya Matsunaga, Yoshiro Niitsu
Cancer science, 96, 3, 149, 56, 3, Mar. 2005, [Peer-reviewed], [International Magazine]
English, Scientific journal, We developed human mesenchymal stem cell (MSC) lines that could differentiate into various tissue cells including bone, neural cells, bone marrow (BM) stromal cells supporting the growth of hematopoietic stem cell (HSC), and so-called 'tumor stromal cells' mixing with tumor cells. We investigated the applicability of MSC as therapeutic cell transplanting reagents (cytoreagents). Telomerized human BM derived stromal cells exhibited a prolonged lifespan and supported the growth of hematopoietic clonogenic cells. The gene transfer of Indian hedgehog (Ihh) remarkably enhanced the HSC expansion supported by the human BM stromal cells. Gene-modified MSC are useful as therapeutic tools for brain tissue damage (e.g. brain infarction) and malignant brain neoplasms. MSC transplantation protected the brain tissue from acute ischemic damage in the midcerebral artery occlusion (MCAO) animal model. Brain-derived neurotrophic factor (BDNF)-gene transduction further enhanced the protective efficacy against the ischemic damage. MSC possessed excellent migratory ability and exerted inhibitory effects on the proliferation of glioma cells. Gene-modification of MSC with therapeutic cytokines clearly augmented the antitumor effect and prolonged the survival of tumor-bearing animals. Gene therapy employing MSC as a tissue-protecting and targeting cytoreagent would be a promising approach.

Expansion of CD34+ cells on telomerized human stromal cells without losing erythroid-differentiation potential in a serum-free condition.
Masayoshi Kobune, Yutaka Kawano, Junji Kato, Yoshinori Ito, Hiroki Chiba, Kiminori Nakamura, Akihito Fujimi, Takuya Matsunaga, Hirofumi Hamada, Yoshiro Niitsu
International journal of hematology, 81, 1, 18, 25, Jan. 2005, [Peer-reviewed], [Domestic magazines]
English, Scientific journal

Mesenchymal stem cells that produce neurotrophic factors reduce ischemic damage in the rat middle cerebral artery occlusion model.
Kazuhiko Kurozumi, Kiminori Nakamura, Takashi Tamiya, Yutaka Kawano, Keiji Ishii, Masayoshi Kobune, Sachie Hirai, Hiroaki Uchida, Katsunori Sasaki, Yoshinori Ito, Kazunori Kato, Osamu Honmou, Kiyohiro Houkin, Isao Date, Hirofumi Hamada
Molecular therapy : the journal of the American Society of Gene Therapy, 11, 1, 96, 104, Jan. 2005, [Peer-reviewed], [International Magazine]
English, Scientific journal

Wnt3 modulates the characteristics and cobblestone area-supporting activity of human stromal cells.
Hiroki Chiba, Masayoshi Kobune, Junji Kato, Yutaka Kawano, Yoshinori Ito, Kiminori Nakamura, Sumiyo Asakura, Hirofumi Hamada, Yoshiro Niitsu
Experimental hematology, 32, 12, 1194, 203, Dec. 2004, [Peer-reviewed], [International Magazine]
English, Scientific journal

Interleukin-11 as an osteoprotegerin-inducing factor in culture medium of blastic cells from a patient with acute megakaryocytic leukemia complicated with osteosclerosis.
Tsutomu Sato, Takuya Matsunaga, Masaya Kida, Kazuhiro Morii, Takuro Machida, Yutaka Kawano, Kiminori Nakamura, Kageaki Kuribayashi, Kohichi Takada, Satoshi Iyama, Yasushi Sato, Tetsuji Takayama, Minoru Takahashi, Junji Kato, Manabu Chokki, Yoshiro Niitsu
American journal of hematology, 77, 1, 62, 6, Sep. 2004, [Peer-reviewed], [International Magazine]
English, Scientific journal

Indian hedgehog gene transfer augments hematopoietic support of human stromal cells including NOD/SCID-beta2m-/- repopulating cells.
Masayoshi Kobune, Yoshinori Ito, Yutaka Kawano, Katsunori Sasaki, Hiroaki Uchida, Kiminori Nakamura, Hironari Dehari, Hiroki Chiba, Rishu Takimoto, Takuya Matsunaga, Takeshi Terui, Junji Kato, Yoshiro Niitsu, Hirofumi Hamada
Blood, 104, 4, 1002, 9, 15 Aug. 2004, [Peer-reviewed], [International Magazine]
English, Scientific journal

Antitumor effect of genetically engineered mesenchymal stem cells in a rat glioma model.
K Nakamura, Y Ito, Y Kawano, K Kurozumi, M Kobune, H Tsuda, A Bizen, O Honmou, Y Niitsu, H Hamada
Gene Therapy, 11, 14, 1155, 1164, Jul. 2004, [Peer-reviewed]
Scientific journal

BDNF gene-modified mesenchymal stem cells promote functional recovery and reduce infarct size in the rat middle cerebral artery occlusion model.
Kazuhiko Kurozumi, Kiminori Nakamura, Takashi Tamiya, Yutaka Kawano, Masayoshi Kobune, Sachie Hirai, Hiroaki Uchida, Katsunori Sasaki, Yoshinori Ito, Kazunori Kato, Osamu Honmou, Kiyohiro Houkin, Isao Date, Hirofumi Hamada
Molecular therapy : the journal of the American Society of Gene Therapy, 9, 2, 189, 97, Feb. 2004, [Peer-reviewed], [International Magazine]
English, Scientific journal

Pre-administration of angiopoietin-1 followed by VEGF induces functional and mature vascular formation in a rabbit ischemic model.
Akihiko Yamauchi, Yoshinori Ito, Masayuki Morikawa, Masayoshi Kobune, Jianhua Huang, Katsunori Sasaki, Kazuhiro Takahashi, Kiminori Nakamura, Hironari Dehari, Yoshiro Niitsu, Tomio Abe, Hirofumi Hamada
The journal of gene medicine, 5, 11, 994, 1004, Nov. 2003, [Peer-reviewed], [International Magazine]
English, Scientific journal

Adenoviral-delivered angiopoietin-1 reduces the infarction and attenuates the progression of cardiac dysfunction in the rat model of acute myocardial infarction.
Kazuhiro Takahashi, Yoshinori Ito, Masayuki Morikawa, Masayoshi Kobune, Jianhua Huang, Masaru Tsukamoto, Katsunori Sasaki, Kiminori Nakamura, Hironari Dehari, Katsuya Ikeda, Hiroaki Uchida, Sachie Hirai, Tomio Abe, Hirofumi Hamada
Molecular therapy : the journal of the American Society of Gene Therapy, 8, 4, 584, 92, Oct. 2003, [Peer-reviewed], [International Magazine]
English, Scientific journal

Myocardial injection of CA promoter-based plasmid mediates efficient transgene expression in rat heart.
Jianhua Huang, Yoshinori Ito, Masayoshi Kobune, Katsunori Sasaki, Kiminori Nakamura, Hironari Dehari, Kazuhiro Takahashi, Katsuya Ikeda, Hiroaki Uchida, Kazunori Kato, Hirofumi Hamada
The journal of gene medicine, 5, 10, 900, 908, Oct. 2003, [Peer-reviewed], [International Magazine]
English, Scientific journal

Inhibition of type I procollagen production by tRNAVal CTE-HSP47 ribozyme.
Seiya Hagiwara, Kiminori Nakamura, Hirofumi Hamada, Katsunori Sasaki, Yoshinori Ito, Kageaki Kuribayashi, Tsutomu Sato, Yasushi Sato, Minoru Takahashi, Katsuhisa Kogawa, Junji Kato, Takeshi Terui, Tetsuji Takayama, Takuya Matsunaga, Kazunari Taira, Yoshiro Niitsu
The journal of gene medicine, 5, 9, 784, 94, Sep. 2003, [Peer-reviewed], [International Magazine]
English, Scientific journal

Telomerized human multipotent mesenchymal cells can differentiate into hematopoietic and cobblestone area-supporting cells.
Masayoshi Kobune, Yutaka Kawano, Yoshinori Ito, Hiroki Chiba, Kiminori Nakamura, Hajime Tsuda, Katsunori Sasaki, Hironari Dehari, Hiroaki Uchida, Osamu Honmou, Sho Takahashi, Akiko Bizen, Rishu Takimoto, Takuya Matsunaga, Junji Kato, Kazunori Kato, Kiyohiro Houkin, Yoshiro Niitsu, Hirofumi Hamada
Experimental hematology, 31, 8, 715, 22, Aug. 2003, [Peer-reviewed], [International Magazine]
English, Scientific journal

Efficient BMP2 gene transfer and bone formation of mesenchymal stem cells by a fiber-mutant adenoviral vector.
Hajime Tsuda, Takuro Wada, Yoshinori Ito, Hiroaki Uchida, Hironari Dehari, Kiminori Nakamura, Katsunori Sasaki, Masayoshi Kobune, Toshihiko Yamashita, Hirofumi Hamada
Molecular therapy : the journal of the American Society of Gene Therapy, 7, 3, 354, 65, Mar. 2003, [Peer-reviewed], [International Magazine]
English, Scientific journal

Ex vivo expansion of human umbilical cord hematopoietic progenitor cells using a coculture system with human telomerase catalytic subunit (hTERT)-transfected human stromal cells.
Yutaka Kawano, Masayoshi Kobune, Miki Yamaguchi, Kiminori Nakamura, Yoshinori Ito, Katsunori Sasaki, Sho Takahashi, Takafumi Nakamura, Hiroki Chiba, Tsutomu Sato, Takuya Matsunaga, Hiroshi Azuma, Kenji Ikebuchi, Hisami Ikeda, Junji Kato, Yoshiro Niitsu, Hirofumi Hamada
Blood, 101, 2, 532, 40, 15 Jan. 2003, [Peer-reviewed], [International Magazine]
English, Scientific journal

Enhanced expression of type IV collagen-binding protein (p29) in Fyn-transfected murine fibrosarcoma cells.
Kazuhiko Koike, Katsuhisa Kogawa, Tetsuji Takayama, Naohito Yoshizaki, Hirohito Muramatsu, Kiminori Nakamura, Sumio Sakamaki, Yoshiro Niitsu
Japanese journal of cancer research : Gann, 93, 10, 1090, 9, Oct. 2002, [Peer-reviewed], [Domestic magazines]
English, Scientific journal

Anti-metastatic gene therapy utilizing subcutaneous inoculation of EC-SOD gene transduced autologous fibroblast suppressed lung metastasis of Meth-A cells and 3LL cells in mice.
M Tanaka, K Kogawa, K Nakamura, Y Nishihori, K Kuribayashi, S Hagiwara, H Muramatsu, S Sakamaki, Y Niitsu
GENE THERAPY, 8, 2, 149, 156, Jan. 2001, [Peer-reviewed]
English, Scientific journal

Enhanced inhibition of experimental metastasis by the combination chemotherapy of Cu-ZnSOD and adriamycin
K Kogawa, H Muramatsu, M Tanaka, Y Nishihori, S Hagiwara, K Kuribayashi, K Nakamura, K Koike, S Sakamaki, Y Niitsu
CLINICAL & EXPERIMENTAL METASTASIS, 17, 3, 239, 244, May 1999, [Peer-reviewed]
English, Scientific journal

Activation of phosphatdylinositol 3-kinase by serum stimulation enhances cell adhesion and cell motility in highly-invasive tongue squamous cell carcinoma cells, SAS-HI
Kazuhiko OKUMURA, Atsushi KONISHI, Tomomi YAMASHITA, Ken OMURA, Maki TANAKA, Tsukasa HAGINO, Kiminori NAKAMURA, Masaaki KANAZAWA
Jpn. J. Ord Maxillofac. Surg., 45, 11, 655, 665, 1999
Scientific journal

Suppression of intracellular Cu-Zn SOD results in enhanced motility and metastasis of Meth A sarcoma cells.
M Tanaka, K Kogawa, Y Nishihori, K Kuribayashi, K Nakamura, H Muramatsu, K Koike, S Sakamaki, Y Niitsu
INTERNATIONAL JOURNAL OF CANCER, 73, 2, 187, 192, Oct. 1997, [Peer-reviewed]
English, Scientific journal

Paneth 細胞・αディフェンシンによる自然免疫機能を介した腸内細菌叢制御　　　　　　　　　　　　　　　
中村公則, 臨床化学 特集：消化管細菌と全身性疾患, 52, 3, 170, Jul. 2023

【腸と健康:腸オルガノイドが挑む次世代バイオモデル】自然免疫と共生を紐解く小腸オルガノイドenteroid
綾部 時芳, 中村 公則, 医学のあゆみ, 270, 11, 1059, 1063, Sep. 2019
医歯薬出版(株), Japanese

【腸内菌叢はコントロールできるか?】抗菌ペプチドαディフェンシンによる腸内細菌叢の制御
中村 公則, 菊池 摩仁, 綾部 時芳, 腸内細菌学雑誌, 33, 3, 129, 135, Jul. 2019
(公財)腸内細菌学会, Japanese

キーワード(No.16) パネート細胞
中村 公則, 消化器病学サイエンス, 3, 1, 43, 43, Mar. 2019
(株)先端医学社, Japanese

クローン病自然発症モデルSAMP1/YitFcマウスの病状進行に伴う腸内細菌叢および糞便メタボライトの変動
小松陽介, 小松陽介, 清水由宇, 山野めぐみ, 中村公則, 綾部時芳, 相沢智康, 相沢智康, 日本生物工学会大会講演要旨集, 71st, 2019

【生体バリア 粘膜や皮膚を舞台とした健康と疾患のダイナミクス】(第1章)生体バリアを支える分子・細胞・組織基盤 細胞分泌物による化学的バリア 抗菌ペプチドによる自然免疫
綾部 時芳, 中村 公則, 実験医学, 35, 7, 1078, 1083, May 2017
(株)羊土社, Japanese

腸における排除と共生 抗菌ペプチドと腸内細菌
綾部 時芳, 櫻木 直也, 中村 公則, 家畜感染症学会誌, 4, 4, 133, 142, Dec. 2015
家畜感染症学会誌編集委員会, Japanese

【生体バリアと生体防御・免疫系】腸上皮細胞の抗菌ペプチドによる自然免疫
中村 公則, 綾部 時芳, 臨床免疫・アレルギー科, 64, 1, 20, 25, Jul. 2015
(有)科学評論社, Japanese

【みえてきた小腸の多彩な機能制御にせまる】抗菌ペプチドは腸内環境を制御できるか
綾部 時芳, 中村 公則, 分子消化器病, 10, 1, 27, 32, Mar. 2013
(株)先端医学社, Japanese

抗体工学による次世代バイオ創薬 薬剤運搬に適した腫瘍標的化抗体のスクリーニング法と創薬シーズ開発　　　　　　　　　　　　　　　
加藤 和則, 中村 公則, 山口 美樹, 濱田 洋文, 日本薬学会年会要旨集, 132年会, 1, 164, 164, Mar. 2012
(公社)日本薬学会, Japanese

【消化管における免疫応答】腸内環境を制御するPaneth細胞αディフェンシン　　　　　　　　　　　　　　　
綾部 時芳, 中村 公則, 臨床免疫・アレルギー科, 57, 1, 25, 31, Jan. 2012
(有)科学評論社, Japanese

【体の中の"小さな生態系"腸内フローラによる免疫ホメオスタシス】αディフェンシンによる腸内細菌制御
中村 公則, 綾部 時芳, 実験医学, 29, 18, 2955, 2961, Nov. 2011
(株)羊土社, Japanese

【IBDの疾患感受性遺伝子を知り、治療につなげる】Paneth細胞とクローン病UPDATE
綾部 時芳, 中村 公則, IBD Research, 5, 2, 108, 112, Jun. 2011
(株)先端医学社, Japanese

【肝癌 基礎・臨床研究のアップデート】肝癌の治療 遺伝子治療 腫瘍の特異的標的化を目指した遺伝子治療法の開発
中村 公則, 濱田 洋文, 日本臨床, 67, 増刊3 肝癌, 560, 564, May 2009
(株)日本臨床社, Japanese

Z33アデノウイルスと抗MCSP抗体を介したメラノーマに対する遺伝子治療(Targeted gene therapy for melanoma using anti-MCSP antibody and Z33 fiber modified adenovirus vectors)　　　　　　　　　　　　　　　
桜木 直也, 中村 公則, 平井 幸恵, 加藤 和則, 濱田 洋文, 日本癌学会総会記事, 67回, 92, 92, Sep. 2008
日本癌学会, English

前立腺癌に対する遺伝子治療標的としてのNCAM2(Neural cell adhesion molecule 2 as a target molecule for prostate cancer gene therapy)　　　　　　　　　　　　　　　
高橋 秀, 加藤 和則, 中村 公則, 濱田 洋文, 日本癌学会総会記事, 67回, 93, 93, Sep. 2008
日本癌学会, English

Interleukin-13 Receptor alpha2 Chain メラノーマの新規標的分子としての検討(Interleukin-13 Receptor alpha2 Chain as a Biomarker and Molecular Target for Melanoma)　　　　　　　　　　　　　　　
中村 公則, 桜木 直也, 加藤 和則, 濱田 洋文, 日本癌学会総会記事, 67回, 498, 498, Sep. 2008
日本癌学会, English

ここまで進んだ抗体のトランスレーショナル・リサーチ、臨床応用 創薬・診断シーズとしての癌標的抗体の作製・選別と応用　　　　　　　　　　　　　　　
加藤 和則, 中村 公則, 濱田 洋文, 基盤的癌免疫研究会総会抄録, 12回, 22, 22, Jun. 2008
日本がん免疫学会, Japanese

スーパー標的抗体によって認識される新規メラノーマ抗原IL-13受容体α2(Super-targeting antibody NS-66 recognizes a novel tumor antigen interleukin-13 receptor alpha 2 on human melamoma)　　　　　　　　　　　　　　　
桜木 直也, 中村 公則, 加藤 和則, 濱田 洋文, 日本癌学会総会記事, 66回, 241, 242, Aug. 2007
日本癌学会, English

前立腺癌遺伝子療法の標的遺伝子の探索(EXPLORATION OF TARGET MOLECULES FOR PROSTATE CANCER GENE THERAPY)　　　　　　　　　　　　　　　
中村 公則, 加藤 和則, 鈴木 一弘, 塚本 泰司, 濱田 洋文, 日本癌学会総会記事, 66回, 246, 246, Aug. 2007
日本癌学会, English

ヒトメラノーマに対する標的化抗体NS-66の樹立と認識抗原解析　　　　　　　　　　　　　　　
加藤 和則, 中村 公則, 桜木 直也, 濱田 洋文, 基盤的癌免疫研究会総会抄録, 11回, 87, 87, May 2007
日本がん免疫学会, Japanese

【がん領域におけるドラッグデリバリーシステム(DDS)】ベッドサイドから見たDDS開発の進歩 DDSを視点とした標的化遺伝子治療
中村 公則, 加藤 和則, 濱田 洋文, 最新医学, 61, 6, 1130, 1137, Jun. 2006
(株)最新医学社, Japanese

Wnt3/Rho経路は多発性骨髄腫における骨髄間質依存性の抗癌剤耐性を惹起する分子機構の一つである　　　　　　　　　　　　　　　
千葉 大樹, 小船 雅義, 河野 豊, 中村 公則, 加藤 和則, 瀧本 理修, 松永 卓也, 加藤 淳二, 濱田 洋文, 新津 洋司郎, 日本血液学会・日本臨床血液学会総会プログラム・抄録集, 67回・47回, 830, 830, Sep. 2005
日本臨床血液学会, Japanese

Wnt3はnon-canonical経路を介して多発性骨髄腫の抗癌剤耐性を増強させる　　　　　　　　　　　　　　　
千葉 大樹, 小船 雅義, 河野 豊, 中村 公則, 加藤 和則, 瀧本 理修, 松永 卓也, 加藤 淳二, 濱田 洋文, 新津 洋司郎, 日本癌学会総会記事, 64回, 371, 371, Sep. 2005
日本癌学会, Japanese

抗PAP2a抗体を用いた膵癌に対する標的化遺伝子治療　　　　　　　　　　　　　　　
中村 公則, 加藤 和則, 濱田 洋文, 日本癌学会総会記事, 64回, 436, 436, Sep. 2005
日本癌学会, Japanese

ヒト多発性骨髄腫に対する抗体を介した標的化遺伝子導入と免疫応答誘導　　　　　　　　　　　　　　　
増田 ゆかり, 加藤 和則, 冨原 圭, 中村 公則, 濱田 洋文, 基盤的癌免疫研究会総会抄録, 9回, 54, 54, Jun. 2005
日本がん免疫学会, Japanese

抗PAP2a抗体を用いた膵癌に対する標的化遺伝子治療　　　　　　　　　　　　　　　
加藤 和則, 中村 公則, 濱田 洋文, 基盤的癌免疫研究会総会抄録, 9回, 55, 55, Jun. 2005
日本がん免疫学会, Japanese

α-GalactosylceramideとアデノIL-2遺伝子治療の併用による抗腫瘍効果および抗転移効果増強の検討　　　　　　　　　　　　　　　
西堀 佳樹, 古川 勝久, 加藤 和則, 田中 真樹, 岡本 哲朗, 竹内 直子, 萩原 誠也, 栗林 景晶, 中村 公則, 新津 洋司郎, 基盤的癌免疫研究会総会抄録, 8回, 67, 67, Jul. 2004
日本がん免疫学会, Japanese

【癌転移のメカニズムと癌治療 その新しいチャレンジ】転移の治療 転移の遺伝子治療
新津 洋司郎, 古川 勝久, 田中 真樹, 中村 公則, 実験医学, 16, 16, 2135, 2138, Oct. 1998
(株)羊土社, Japanese

食品免疫学事典 日本食品免疫学会(編)　　　　　　　　　　　　　　　
抗菌ペプチド／ディフェンシン
朝倉書店, 10 Nov. 2021, [Contributor]

Understanding the symbiotic mechanism between the intestinal microbiota and the host regulated by Paneth cell α-defensin　　　　　　　　　　　　　　　
中村公則
日本農芸化学会 2025年度大会 シンポジウム「腸内細菌叢一宿主クロストークの仲介者たち」, 07 Mar. 2025, Nominated symposium
04 Mar. 2025 - 09 Mar. 2025, 札幌コンベンションセンター, [Invited]

腸内環境を守るPaneth細胞･αディフェンシンの健康と疾患における役割　　　　　　　　　　　　　　　
中村公則
2024年度 第3回 生活習慣病予防のための機能性食品開発に関する研究会, 03 Dec. 2024, Public discourse
[Invited]

抗菌ペプチド･αディフェンシンが制御する腸内細菌叢形成　　　　　　　　　　　　　　　
中村公則
日本食品免疫学会設立20周年記念学術大会 シンポジウム1「食品免疫学を支える科学的エビデンス」, 02 Dec. 2024, Nominated symposium
[Invited]

食物アレルギー発症における異常Paneth細胞の関与　　　　　　　　　　　　　　　
原澤頑太, 大平修也, 横井友樹, 竹見祥大, 井原海詩, 阿部悠和, 中村公則
日本食品免疫学会設立20周年記念学術大会, 02 Dec. 2024, Poster presentation

The effect of psychological stress induced by social isolation on Crohn's disease relapse.　　　　　　　　　　　　　　　
Miu Ihara, Shuya Ohira, Yuki Yokoi, Shota Takemi, Yuna Abe, Kanta Harasawa, Ryo Matsushita, Kiminori Nakamura
第47回日本分子生物学会年会, 28 Nov. 2024, Poster presentation

腸内細菌叢を制御する Paneth細胞･αディフェンシン　　　　　　　　　　　　　　　
中村公則
2024年度 第2回 先端研究推進センターセミナー（北海道医療大学）, 07 Nov. 2024, Public discourse
[Invited]

Paneth細胞･αディフェンシンが制御する腸内細菌叢形成からみた健康と病気　　　　　　　　　　　　　　　
中村公則
第83回日本公衆衛生学会総会 ランチョンセミナー, 30 Oct. 2024, Public discourse

αディフェンシンが担う腸内細菌叢の形成からみた母子の健康　　　　　　　　　　　　　　　
中村公則
2024年度JFPA/日本DOHaD学会共催セミナー, 12 Oct. 2024, Public discourse
[Invited]

Paneth 細胞･αディフェンシンの腸内細菌叢制御による健康と疾患　　　　　　　　　　　　　　　
中村公則
第28回腸内細菌学会学術集会 シンポジウム「腸内環境研究の最前線」, 26 Jun. 2024, Nominated symposium
25 Jun. 2024 - 26 Jun. 2024, [Invited]

Paneth cell･α-defensin to regulate gut microbiota in health and disease　　　　　　　　　　　　　　　
中村公則
第24回日本抗加齢医学会総会 シンポジウム 「口腔細菌から始める アンチエイジング医学」, 01 Jun. 2024, Nominated symposium
31 May 2024 - 02 Jun. 2024, 熊本城ホール, [Invited]

Selective Paneth cell granule secretion in response to pathogenic and commensal bacteria in enteric mucosal immunity　　　　　　　　　　　　　　　
Yuki Yokoi, Shuya Ohir, Haruto Matsuoka, Shota Takemi, Tokiyoshi Ayabe, Kiminori Nakamura
The 52nd Annual Meeting of the Japanese Society for Immunology, 18 Jan. 2024, Poster presentation
17 Jan. 2024 - 19 Jan. 2024

腸内細菌叢を制御するαディフェンシンからみた健康と疾病　　　　　　　　　　　　　　　
中村公則
KyotoIBD Special Seminar, 18 Dec. 2023, Public discourse
[Invited]

Establishment of a high-efficient method for generating transgenic enteroid revealing intestinal epithelial function　　　　　　　　　　　　　　　
松下稜, 横井友樹, 大平修也, 松岡温音, 竹見祥大, 中村公則
第46回日本分子生物学会年会, 06 Dec. 2023, Poster presentation
27 Nov. 2023 - 01 Dec. 2023

Paneth細胞・αディフェンシンによる腸内環境制御と健康維持　　　　　　　　　　　　　　　
中村公則
iSeminar（異分野融合研究セミナー）, 22 Nov. 2023, Invited oral presentation
[Invited]

Paneth細胞・αディフェンシンによる自然免疫機能を介した腸内細菌叢制御　　　　　　　　　　　　　　　
中村公則
日本食品免疫学会第19回学術大会 シンポジウム「腸内環境と免疫システム」, 14 Nov. 2023
[Invited]

授乳期の食事・母乳栄養成分・乳児の発育」の関連性～岩見沢母子健康調査（SMILE Iwamizawa）における産後1ヶ月時点の解析～　　　　　　　　　　　　　　　
小松陽介, 和田泰明, 田畑風華, 川上智美, 武田安弘, 中村公則, 綾部時芳, 中村幸志, 木村尚史, 玉腰暁子
第11回日本DOHaD学会学術集会, Aug. 2023

Paneth細胞 αディフェンシンによる腸内細菌共生メカニズムと疾患　　　　　　　　　　　　　　　
中村公則
第３章腸内微生物叢研究の最前線シリーズ, 24 Jul. 2023
[Invited]

抗菌ペプチドαディフェンシンによる自然免疫機能を介した腸内細菌制御と健康　　　　　　　　　　　　　　　
中村公則
第2回長崎感染症特別講演会, 19 Jun. 2023
[Invited]

Paneth細胞αディフェンシンが担う腸内細菌叢の形成からみた母子の疾患リスク上昇メカニズムの理解　　　　　　　　　　　　　　　
中村公則
第77回日本栄養･食糧学会大会 シンポジウム「栄養環境による腸内細菌叢変動から見た母子の健康～北海道大学 COI・岩見沢母子健康調査における取り組み～」, 14 May 2023, Nominated symposium
[Invited]

Paneth細胞・αディフェンシンによる自然免疫機能を介した腸内細菌叢制御　　　　　　　　　　　　　　　
中村公則
第11回自然免疫シンポジウム「アンチエイジングと自然免疫」, 10 Mar. 2023, Invited oral presentation
[Invited]

High-efficient genetic engineering of enteroids using mouse isolated crypts revealing the intestinal function,　　　　　　　　　　　　　　　
大平修也, 横井友樹, 海堀唯人, 清水由宇, 綾部時芳, 中村公則
第51回日本免疫学会学術集会, 08 Dec. 2022, Poster presentation

腸管恒常性維持における病原菌と常在菌の選択的センシングによるPaneth細胞顆粒分泌調節　　　　　　　　　　　　　　　
横井友樹, 大平修也, 松岡温音, 海堀唯人, 篠崎竜我, 綾部時芳, 中村公則
第45回日本分子生物学会, 02 Dec. 2022, Public symposium

食品が誘導するPaneth細胞αディフェンシンによる免疫と共生　　　　　　　　　　　　　　　
綾部 時芳, 横井 友樹, 高桑 暁子, 中村 公則
第18回日本食品免疫学会学術大会, 09 Nov. 2022

抗菌ペプチドαディフェンシンによる腸内細菌制御と健康　　　　　　　　　　　　　　　
綾部時芳, 横井友樹, 清水由宇, 中村公則
日本食品・機械研究会, 28 Feb. 2022, Invited oral presentation

Paneth細胞αディフェンシンによる腸内細菌形成からみた健康と病気　　　　　　　　　　　　　　　
中村公則
東洋大学 ライフイノベーション研究所2021年シンポジウム「免疫と健康維持・増進」, 20 Nov. 2021, Invited oral presentation
20 Nov. 2021 - 04 Dec. 2021, [Invited]

Simple and efficient genetic engineering of enteroids by using mouse isolated crypts．　　　　　　　　　　　　　　　
Shuya Ohira, Yuki Yokoi, Mani Kikuchi, Natsumi Yatsuzuka, Tokiyoshi Ayabe, Kiminori Nakamura
第44回日本分子生物学会年会, 03 Dec. 2021, Oral presentation

The mechanism for effects of maternal high-fat diet on the development of Paneth cells in offspring　　　　　　　　　　　　　　　
八塚夏美, 杉本 理菜, 大平 修也, 横井友樹, 菊池摩仁, 綾部時芳, 中村公則
第44回日本分子生物学会年会, 02 Dec. 2021, Poster presentation

Paneth細胞顆粒分泌応答からみた食機能評価系の確立　　　　　　　　　　　　　　　
横井友樹, 中村公則, 高桑暁子, 菊池摩仁, 綾部時芳
第17回日本食品免疫学会学術大会, 16 Nov. 2021
16 Nov. 2021 - 17 Nov. 2021, 東京都

Paneth細胞αディフェンシンが担う腸内細菌叢の形成からみた生体恒常性の維持機構　　　　　　　　　　　　　　　
中村 公則, 綾部 時芳
第24回 日本臨床腸内微生物学会総会, 28 Aug. 2021, Nominated symposium
28 Aug. 2021, [Invited]

抗菌ペプチドから粘膜免疫を理解する　　　　　　　　　　　　　　　
綾部時芳, 横井友樹, 中村公則
第58回日本消化器免疫学会, 03 Jul. 2021

ER-Stress-Associated Misfolding of Paneth cell α-defensin Induces Dysbiosis and ileitis in a Murine Model of Crohn’s Disease　　　　　　　　　　　　　　　
Yu Shimizu, Kiminori Nakamura, Aki Yoshii, Yuki Yokoi, Mani Kikuchi, Ryuga Shinozaki, Shunta Nakamura, Shuya Ohira, Rina Sugimoto, Tokiyoshi Ayabe
World Microbe Forum, 21 Jun. 2021, Poster presentation

Dynamics of Paneth Cell Granule Secretory Responses to Bacteria in Innate Enteric Immunity　　　　　　　　　　　　　　　
Yuki Yokoi, Kiminori Nakamura, Shuya Ohira, Ryuga Shinozaki, Mani Kikuchi, Tokiyoshi Ayabe
World Microbe Forum, 21 Jun. 2021, Poster presentation

霊長類T1R1およびT1R2抗体の作製　　　　　　　　　　　　　　　
小松さゆり, 中安亜希, 大島永心, 新藤壮剛, 今井啓雄, 伯川美穂, 杉山宗太郎, 綾部時芳, 中村公則, 山根拓実, 大石祐一, 岩槻健
日本農芸化学会 2021年度大会, 19 Mar. 2021, Oral presentation
18 Mar. 2021 - 21 Mar. 2021

Immunopathological features of chronic ileitis in Crohn’s disease model SAMP1/YitFc mouse　　　　　　　　　　　　　　　
村山綾菜, 中村公則, 菊池摩仁, 横井友樹, 綾部時芳
The 43th Annual Meeting of Molecular Biology Society of Japan, 04 Dec. 2020, Oral presentation
02 Dec. 2020 - 04 Dec. 2020

Paneth細胞αディフェンシンによる腸内細菌叢制御を介した生体恒常性の維持機構　　　　　　　　　　　　　　　
中村公則, 綾部時芳
第75回 日本体力医学会大会, 24 Sep. 2020, Nominated symposium
24 Sep. 2020 - 26 Sep. 2020, [Invited]

Alpha-defensin異常による腸内細菌叢の破綻とIBD　　　　　　　　　　　　　　　
綾部時芳, 清水由宇, 中村公則
第127回日本消化器病学会北海道支部例会, 05 Sep. 2020

Understanding mechanisms of disease development via disrupted Paneth cell development involving maturation and formation of intestinal microbiota in early life stage　　　　　　　　　　　　　　　
中村公則, 綾部時芳
第24回 腸内細菌学会学術集会, 12 Jun. 2020, Nominated symposium
11 Jun. 2020 - 12 Jun. 2020, [Invited]

Impact of sample storage conditions on NMR-based human fecal metabolomics　　　　　　　　　　　　　　　
宋 子豪, 包 克非, 北田直也, 清水由宇, 菊池摩仁, 熊木康裕, 大西裕季, 塚本 卓, 菊川峰志, 出村 誠, 中村公則, 綾部時芳, 山村凌大, 中村幸志, 玉腰暁子, 相沢智康
第24回 腸内細菌学会学術集会, 11 Jun. 2020, Oral presentation
11 Jun. 2020 - 12 Jun. 2020

Association between lean, obesity and gut microbiota in a general Japanese population: The DOSANCO Health Study　　　　　　　　　　　　　　　
木村尚史, 山村凌大, 檜森亮吾, 鵜川重和, 中村幸志, 中川貴史, 今江章宏, 國弘忠生, 朴鐘旭, Attayeb Mohsen, 川島和, 清水由宇, 中村公則, 綾部時芳, 玉腰暁子
第24回 腸内細菌学会学術集会, 11 Jun. 2020, Oral presentation
11 Jun. 2020 - 12 Jun. 2020

Association between archaea and obesity in a general Japanese population: The DOSANCO Health Study　　　　　　　　　　　　　　　
山村凌大, 鵜川重和, 中村幸志, 木村尚史, 中川貴史, 今江章宏, 國弘忠生, 朴鐘旭, Attayeb Mohsen, 川島和, 清水由宇, 中村公則, 綾部時芳, 玉腰暁子
第24回 腸内細菌学会学術集会, 11 Jun. 2020, Oral presentation
11 Jun. 2020 - 12 Jun. 2020

Statistical analysis for the effect of mulberry leaf containing diet on the temporal change of α-defensin and intestinal microbiota　　　　　　　　　　　　　　　
子安惟, 中岡慎治, 菊池摩仁, 中村公則, 綾部時芳
第24回 腸内細菌学会学術集会, 11 Jun. 2020, Oral presentation
11 Jun. 2020 - 12 Jun. 2020

膵癌初期発生における膵腸相関　　　　　　　　　　　　　　　
小野裕介, 中村公則, 清水由宇, 横井友樹, 杉本理菜, 早川祐子, 佐藤裕基, 水上裕輔, 奥村利勝, 綾部時芳
第24回 腸内細菌学会学術集会, 11 Jun. 2020, Oral presentation
11 Jun. 2020 - 12 Jun. 2020

Paneth cell dysfunction involved in development of nonalcoholic steatohepatitis through disruption of the intestinal microbiota　　　　　　　　　　　　　　　
中村駿太, 中村公則, 菊池摩仁, 横井友樹, 大平修也, 清水由宇, 西田琢人, 綾部時芳
第24回 腸内細菌学会学術集会, 11 Jun. 2020, Oral presentation
11 Jun. 2020 - 12 Jun. 2020

Influence of intestinal environment on bactericidal activity of α-defensin isoform　　　　　　　　　　　　　　　
篠崎竜我, 中村公則, 清水由宇, 綾部時芳
第24回 腸内細菌学会学術集会, 11 Jun. 2020, Oral presentation
11 Jun. 2020 - 12 Jun. 2020

Mechanisms of microbial colonization regulated by Paneth cell development from early postnatal period　　　　　　　　　　　　　　　
西田琢人, 中村公則, 横井友樹, 綾部時芳
第24回 腸内細菌学会学術集会, 11 Jun. 2020, Oral presentation
11 Jun. 2020 - 12 Jun. 2020

多様なα-defensin isoformに対するin vitroにおける効率的なS-S結合導入法の確立　　　　　　　　　　　　　　　
篠崎竜我, 中村公則, 清水由宇, 綾部時芳
第42 回日本分子生物学会年会, 03 Dec. 2019, Poster presentation
03 Dec. 2019 - 06 Dec. 2019

桑葉のα-defensin分泌促進効果と腸内細菌叢制御　　　　　　　　　　　　　　　
菊池摩仁, 中村公則, 綾部時芳
日本食品免疫学会 設立15周年記念学術大会, 19 Nov. 2019, Poster presentation
19 Nov. 2019 - 20 Nov. 2019

The influence of maternal high-fat intake on the regulation of intestinal environment by Paneth cell α-defensin in offsprings　　　　　　　　　　　　　　　
杉本理菜, 中村公則, 嶋 七海, 清水由宇, 横井友樹, 綾部時芳
日本農芸化学会 2019年度大会, 27 Mar. 2019, Oral presentation
24 Mar. 2019 - 27 Mar. 2019

Involvement of Paneth cell alpha-defensin misfolding in disease progression of SAMP1/YitFc, a murine model of Crohn's disease.　　　　　　　　　　　　　　　
Yu Shimizu, Kiminori Nakamura, Mani Kikuchi, Tokiyoshi Ayabe
第47回 日本免疫学会学術集会, 12 Dec. 2018, Poster presentation
10 Dec. 2018 - 12 Dec. 2018

腸管organoidを用いたPaneth細胞分化制御機構の解析　　　　　　　　　　　　　　　
大平修也, 中村公則, 菊池摩仁, 横井友樹, 杉本理菜, 綾部時芳
第41回 日本分子生物学会年会, 30 Nov. 2018, Poster presentation
28 Nov. 2018 - 30 Nov. 2018

レスベラトロール摂取によるα-defensin 分泌量と腸内細菌叢への影響　　　　　　　　　　　　　　　
中村公則, 杉本理菜, 横井友樹, 清水由宇, 菊池摩仁, 綾部時芳
第14回 日本食品免疫学会学術大会, 15 Nov. 2018, Poster presentation
15 Nov. 2018 - 16 Nov. 2018

封入体共発現を利用した大量発現系において抗菌ペプチドcryptdin familyの生産性を決定する因子の解析　　　　　　　　　　　　　　　
保本美穂子, 平峰里菜, SONG Yuchi, 佐藤優次, 塚本卓, 塚本卓, 菊川峰志, 菊川峰志, 出村誠, 出村誠, 中村公則, 綾部時芳, 相沢智康, 相沢智康
第18回 日本蛋白質科学会年会, 27 Jun. 2018, Poster presentation
26 Jun. 2018 - 28 Jun. 2018

Paneth細胞が制御する腸内環境の機能解明　　　　　　　　　　　　　　　
中村公則
第95回 北海道腸疾患研究会, 16 Jun. 2018, Keynote oral presentation
16 Jun. 2018, [Invited]

小腸オルガノイドを利用した排出系トランスポーターの基質関与探索ツールの構築　　　　　　　　　　　　　　　
佐藤夕紀, 中村公則, 小関千尋, 石川岳彦, 島田美紀子, 横井友樹, 本間直幸, 森山隆則, 菅原満
第13回 トランスポーター研究会年会, 21 May 2018, Poster presentation
21 May 2018 - 22 May 2018

Enteroidを用いたPaneth細胞が制御する腸内環境の 機能解明　　　　　　　　　　　　　　　
中村公則, 横井友樹, 米田司, 綾部時芳
日本農芸化学会 2018年度大会, 18 Mar. 2018, Nominated symposium
15 Mar. 2018 - 18 Mar. 2018, [Invited]

エンテロイドを用いた新規・食品機能性成分評価法の構築　　　　　　　　　　　　　　　
中村公則
北大リサーチ&ビジネスパークセミナー ~北海道発！「食」から「健康」へ~, 07 Feb. 2018, Keynote oral presentation
[Invited]

Evaluation system for receptor expression and function in the intestinal stem cell niche　　　　　　　　　　　　　　　
Rina Sugimoto, Naoya Sakuragi, Yuki Yokoi, Kiminori Nakamura, Tokiyoshi Ayabe
The 46th Annual Meeting of The Japanese Society for Immunology, 12 Dec. 2017, Poster presentation
12 Dec. 2017 - 14 Dec. 2017

Paneth cell α-defensin misfolding in SAMP1/YitFc, a murine model of Crohn's disease　　　　　　　　　　　　　　　
清水 由宇, 中村 公則, 菊池 摩仁, 櫻木 直也, 綾部 時芳
第40回 日本分子生物学会年会, 09 Dec. 2017, Poster presentation
06 Dec. 2017 - 09 Dec. 2017

Establishment of the evaluation system for Paneth cell granule secretion by using enteroid with lumen microinjection and its application　　　　　　　　　　　　　　　
米田司, 中村公則, 横井友樹, 大平修也, 菊池摩仁, 櫻木直也, 綾部時芳
第40回 日本分子生物学会年会, 06 Dec. 2017, Poster presentation
06 Dec. 2017 - 09 Dec. 2017

高純度ソーティング由来cDNAライブラリーを用いたPaneth細胞の新規機能探索　　　　　　　　　　　　　　　
櫻木 直也, 中村 公則, 横井 友樹, 菊池 摩仁, 綾部 時芳
第13回 日本食品免疫学会学術大会, 09 Nov. 2017, Poster presentation
09 Nov. 2017 - 10 Nov. 2017

腸内環境を制御する抗菌ペプチドα-defensinと疾患　　　　　　　　　　　　　　　
中村公則
日本薬局協励会北海道合同支部「学術繋栄講座」, 09 Jul. 2017, Keynote oral presentation
[Invited]

Mutation analysis of cryptdin-4, antimicrobial peptide from mouse
平峰里菜, 久米田博之, 久米田博之, 熊木康裕, 菊川峰志, 菊川峰志, 出村誠, 出村誠, 中村公則, 綾部時芳, 相沢智康
日本農芸化学会 2017年度大会, 20 Mar. 2017, Japanese, Poster presentation
17 Mar. 2017 - 20 Mar. 2017

Enteroidを用いたPaneth細胞顆粒分泌反応の可視化解析による機序解明　　　　　　　　　　　　　　　
横井友樹, 中村公則, 櫻木直也, 菊池摩仁, 綾部時芳
第12回 日本食品免疫学会学術大会, 09 Nov. 2016, Poster presentation
09 Nov. 2016 - 10 Nov. 2016

Enteroidを用いたPaneth細胞の機能可視化～顆粒分泌･再形成および免疫系クロストーク　　　　　　　　　　　　　　　
綾部時芳, 横井友樹, 櫻木直也, 中村公則
日本農芸化学会 2016年度大会, 30 Mar. 2016, Invited oral presentation
27 Mar. 2016 - 30 Mar. 2016

アミノ酸がパネト細胞αディフェンシンに与える影響　　　　　　　　　　　　　　　
高桑暁子, 中村公則, 櫻木直也, 綾部時芳
日本農芸化学会 2016年度大会, 30 Mar. 2016
27 Mar. 2016 - 30 Mar. 2016

腸からみれば！ 食品と免疫と腸内細菌がつくる“腸内環境”の解明と実用化　　　　　　　　　　　　　　　
綾部時芳, 櫻木直也, 中村公則
日本農芸化学会 2016年度大会, 29 Mar. 2016, Invited oral presentation
27 Mar. 2016 - 30 Mar. 2016

クローン病モデルマウスSAMP1/YitFcの病態形成におけるα-defensinの関与　　　　　　　　　　　　　　　
吉井彩季, 中村公則, 櫻木直也, 綾部時芳
第38回 日本分子生物学会年会, 01 Dec. 2015, Poster presentation
01 Dec. 2015 - 04 Dec. 2015

腸管星細胞株を用いた腸管線維化機序の解析　　　　　　　　　　　　　　　
菅原徹也, 中村公則, 櫻木直也, 綾部時芳
第38回 日本分子生物学会年会, 01 Dec. 2015, Poster presentation
01 Dec. 2015 - 04 Dec. 2015

放射線腸炎の指標としての便中αディフェンシンの可能性～マウスでの研究結果から～　　　　　　　　　　　　　　　
小野寺俊輔, 中村公則, 西山典明, 綾部時芳, 白��博樹
第133回 日本医学放射線学会北日本地方会・第78回 日本核医学会北日本地方会, 23 Oct. 2015, Oral presentation
23 Oct. 2015 - 24 Oct. 2015

大麦若葉末がαディフェンシン分泌に与える影響　　　　　　　　　　　　　　　
森川琢海, 北村整一, 鍔田仁人, 山口和也, 高橋欣也, 櫻木直也, 中村公則, 綾部時芳
日本食品化学工学会 第62回大会, 28 Aug. 2015
27 Aug. 2015 - 29 Aug. 2015

αディフェンシンが規定する新しい腸内環境の可能性　　　　　　　　　　　　　　　
中村 公則
第5回 オルソオルガノジェネシス検討会, 06 Aug. 2015
[Invited]

成長に伴うマウスの腸内細菌叢や抗菌ペプチドα－ディフェンシンの変化及びその関係　　　　　　　　　　　　　　　
佐藤拓海, 中村公則, 菅原宏佑, 加藤久美子, 岩淵紀介, 小田巻俊孝, 清水(肖)金忠, 阿部文明, 綾部時芳
日本乳酸菌学会 2015年度大会, 12 Jul. 2015, Oral presentation
11 Jul. 2015 - 12 Jul. 2015

基質の硬さによって促進される大腸がん細胞の悪性化:転写因子YAPを介した基質分解酵素MMP-7の発現亢進　　　　　　　　　　　　　　　
温田晃弘, 石原誠一郎, 水谷武臣, 中村公則, 綾部時芳, 川端和重, 芳賀永
第67回 日本細胞生物学会大会, 30 Jun. 2015
30 Jun. 2015 - 02 Jul. 2015

クローン病モデルマウスSAMP1/YitFcの病態形成におけるα-defensinの関与　　　　　　　　　　　　　　　
吉井 彩季, 中村 公則, 櫻木 直也, 綾部 時芳
第19回 腸内細菌学会, 18 Jun. 2015, Poster presentation
18 Jun. 2015 - 19 Jun. 2015

αディフェンシンが規定する新しい腸内環境の可能性　　　　　　　　　　　　　　　
中村 公則
北海道大学フード＆メディカルイノベーション国際拠点開設記念 食と腸内環境 学術講演会「新しい腸内環境から考える健康」, 02 Jun. 2015
[Invited]

クローン病モデルマウスSAMP1/Yitの病態進行とα-defensinの分泌異常　　　　　　　　　　　　　　　
中村 公則, 櫻木 直也, 綾部 時芳
第101回 日本消化器病学会総, 25 Apr. 2015

組織常在型M2マクロファージの培養系の確立と間葉系細胞への影響の検討　　　　　　　　　　　　　　　
藤岡明博, 櫻木直也, 中村公則, 古澤和也, 綾部時芳, 佐々木直樹, 福井彰雅
平成26年度北大細胞生物研究集会, 03 Mar. 2015, Oral presentation
03 Mar. 2015

同位体顕微鏡で小腸の吸収機能を視る　　　　　　　　　　　　　　　
櫻木直也, 中村公則, 綾部時芳, 永田康祐, 坂本直哉, 圦本尚義
第6回 安定同位元素イメージング技術による産業イノベーションシンポジウム, 02 Mar. 2015, Oral presentation
02 Mar. 2015

抗菌ペプチドαディフェンシンによる腸内環境の恒常性制御と疾病　　　　　　　　　　　　　　　
綾部時芳, 櫻木直也, 中村公則
第20回日本エンドトキシン・自然免疫研究会, 06 Dec. 2014, Invited oral presentation
05 Dec. 2014 - 06 Dec. 2014

高脂肪食による肥満における抗菌ペプチドα-defensin分泌の関与　　　　　　　　　　　　　　　
第37回 日本分子生物学会年会, 26 Nov. 2014, Poster presentation
25 Nov. 2014 - 27 Nov. 2014

組織常在型M2マクロファージ細胞の培養系の確立と間葉系細胞への影響について　　　　　　　　　　　　　　　
藤岡明博, 櫻木直也, 中村公則, 古澤和也, 佐々木直樹, 綾部時芳, 福井彰雅
第37回 日本分子生物学会年会, 26 Nov. 2014, Poster presentation
25 Nov. 2014 - 27 Nov. 2014

Paneth細胞α-defensinによる腸内細菌叢制御と疾患との関連の解明　　　　　　　　　　　　　　　
中村 公則, 櫻木 直也, 綾部 時芳
2014年度 生理学研究所研究会 「粘膜免疫学と膜輸送生理学の融合」, 27 Oct. 2014
[Invited]

短鎖脂肪酸がパネト細胞αディフェンシン分泌に与える影響　　　　　　　　　　　　　　　
高桑暁子, 中村公則, 櫻木直也, 綾部時芳
日本食品免疫学会 第10回学術大会, 16 Oct. 2014, Poster presentation
16 Oct. 2014 - 17 Oct. 2014

大腸がん細胞において基質の硬さはミオシンのリン酸化を通じて基質分解酵素MMP7の発現を亢進する　　　　　　　　　　　　　　　
温田晃弘, 石原誠一郎, 中村公則, 綾部時芳, 芳賀永
第73回日本癌学会学術総会, 27 Sep. 2014, Poster presentation
25 Sep. 2014 - 27 Sep. 2014

NMR analysis of the oligomerization mechanism of antimicrobial peptide human defensin 5
Hashimoto Arata, Tomisawa Satoshi, Kamiya Masakatsu, Kikukawa Takashi, Kumaki Yasuhiro, Nakamura Kiminori, Ayabe Tokiyoshi, Aizawa Tomoyasu, Demura Makoto
第52回 日本生物物理学会年会, 27 Sep. 2014, The Biophysical Society of Japan General Incorporated Association, English, Poster presentation
25 Sep. 2014 - 27 Sep. 2014

腸内細菌を制御するαディフェンシンから疾病を眺める.　　　　　　　　　　　　　　　
綾部時芳, 櫻木直也, 中村公則
第51回 日本消化器免疫学会総会, 10 Jul. 2014, Invited oral presentation
10 Jul. 2014 - 11 Jul. 2014

Novel methods for evaluating Paneth cell functions using small intestinal organoids and sandwich ELISA for -defensin in mouse.　　　　　　　　　　　　　　　
Sasaki K, Nakamura K, Sakuragi N, Ayabe T
第36回 日本分子生物学会年会, 05 Dec. 2013, Poster presentation
03 Dec. 2013 - 06 Dec. 2013

αディフェンシンによる腸内環境の制御 －その破綻は疾病を招くか－　　　　　　　　　　　　　　　
綾部時芳, 櫻木直也, 中村公則
第8回遺伝子栄養学研究会学術集会, 02 Aug. 2013, Invited oral presentation

Development of antifibrotic therapy targeted to stellate cells for intestinal fibrosis in Crohn's disease.　　　　　　　　　　　　　　　
金野真奈, 中村公則, 中村公則, 丸山景資, 綾部時芳, 綾部時芳
第35回 日本分子生物学会年会, 13 Dec. 2012, Poster presentation
11 Dec. 2012 - 14 Dec. 2012

Deficiency of secreted cryptdin-4 detected in a mouse model of Crohn’s disease using a new sandwich ELISA.　　　　　　　　　　　　　　　
Nakamura K, Kuroishi A, Kono M, Kobayashi M, Ayabe T
Experimental Biology 2012, 25 Apr. 2012, Poster presentation
21 Apr. 2012 - 25 Apr. 2012, San Diego, United States, [International presentation]

Development of antifibrotic therapy for intestinal fibrosis targeted to stellate cells.　　　　　　　　　　　　　　　
Yoshioka S, Nakamura K, Maruyama K, Ayabe T
第34回 日本分子生物学会年会, 14 Dec. 2011, Oral presentation

Foods-induced innate immune responses of Paneth cell -defensin uncover novel functions of foods.　　　　　　　　　　　　　　　
Ayabe T, Kuroishi A, Kobayashi M, Nakamura K
International Society for Nutraceuticals and Functional Foods Annual Conference (ISNFF2011)., 17 Nov. 2011, Nominated symposium
14 Nov. 2011 - 17 Nov. 2011, [International presentation]

佐藤真希、平 敏夫、中村公則、綾部時芳、福井彰雅　　　　　　　　　　　　　　　
佐藤真希, 平 敏夫, 中村公則, 綾部時芳, 福井彰雅
日本動物学会第82回大会, 21 Sep. 2011, Poster presentation

Selection and regulation of intestinal microbiota by Paneth cell -defensins.　　　　　　　　　　　　　　　
Ayabe T, Nakamura K
XIII International Union of Microbiological Societies 2011 Congress (IUMS2011), 08 Sep. 2011, Nominated symposium
06 Sep. 2011 - 16 Sep. 2011, [International presentation]

パネト細胞αディフェンシンによる腸内細菌の制御からみた共生の新展開　　　　　　　　　　　　　　　
綾部時芳, 吉岡佐和子, 小林美智代, 中村公則
第6回核酸・核タンパク機能性研究会学術集会（恵庭フォーラム）, 08 Aug. 2011, Oral presentation

Isolation of intermediate stellate cells in the mouse small intestine.　　　　　　　　　　　　　　　
Yoshioka S, Nakamura K, Sakai N, Ayabe T
第33回 日本分子生物学会年会, 10 Dec. 2010, Poster presentation

Regulation of microbiota by antimicrobial peptides in the gut.　　　　　　　　　　　　　　　
Ayabe T, Masuda K, Nakamura K, Sakai N
7th. International Symposium on Tonsil and Mucosal Barriers of the Upper Airways (ISTMB), Symposium-1 (Innate and Adoposal Immunology), 07 Jul. 2010, Nominated symposium
07 Jul. 2010 - 09 Jul. 2010, [International presentation]

Selective bactericidal activity of the mouse α-defensin, cryptdin-4 against commensal and non-commensal bacteria.　　　　　　　　　　　　　　　
Masuda K, Sakai N, Nakamura K, Ayabe T
14th International Congress of Immunology., 07 Jul. 2010, Poster presentation
07 Jul. 2010 - 09 Jul. 2010, [International presentation]

Paneth cells and antimicrobial peptides, α-defensins, in enteric innate immunity.　　　　　　　　　　　　　　　
Ayabe T, Masuda K, Nakamura K, Sakai N
6th. Annual Meeting of Japanese Association for Food Immunology, Symposium-2 (International Symposium on Dietary modulation of mucosal barrier and infection), 02 Jun. 2010, Nominated symposium
01 Jun. 2010 - 02 Jun. 2010, [International presentation]

Regulation of intestinal microbiota by Paneth cell α-defensins.　　　　　　　　　　　　　　　
Ayabe T, Masuda K, Nakamura K, Sakai N
The83rd Annual Meeting of Japanese Society for Bacteriology, International Symposium, 27 Mar. 2010
27 Mar. 2010 - 29 Mar. 2010, [International presentation]

マウス小腸における星細胞の同定　　　　　　　　　　　　　　　
吉岡佐和子, 中村公則, 坂井直樹, 綾部時芳
平成21年度 北大細胞生物研究集会, 09 Mar. 2009, Oral presentation

Interleukin-13 Receptor alpha2 Chain メラノーマの新規標的分子としての検討(Interleukin-13 Receptor alpha2 Chain as a Biomarker and Molecular Target for Melanoma)　　　　　　　　　　　　　　　
中村 公則, 桜木 直也, 加藤 和則, 濱田 洋文
日本癌学会総会記事, Sep. 2008, 日本癌学会, English
Sep. 2008 - Sep. 2008

前立腺癌に対する遺伝子治療標的としてのNCAM2(Neural cell adhesion molecule 2 as a target molecule for prostate cancer gene therapy)　　　　　　　　　　　　　　　
高橋 秀, 加藤 和則, 中村 公則, 濱田 洋文
日本癌学会総会記事, Sep. 2008, 日本癌学会, English
Sep. 2008 - Sep. 2008

Z33アデノウイルスと抗MCSP抗体を介したメラノーマに対する遺伝子治療(Targeted gene therapy for melanoma using anti-MCSP antibody and Z33 fiber modified adenovirus vectors)　　　　　　　　　　　　　　　
桜木 直也, 中村 公則, 平井 幸恵, 加藤 和則, 濱田 洋文
日本癌学会総会記事, Sep. 2008, 日本癌学会, English
Sep. 2008 - Sep. 2008

Bystander effect between mesenchymal stem cells and brain tumor cells in the HSVTK/GCV system is not species specific　　　　　　　　　　　　　　　
Hiroshi Kosaka, Tomotsugu Ichikawa, Hirokazu Kambara, Satoshi Inoue, Tomoko Maruo, Kazuhiko Kurozumi, Kimi-nori Nakamura, Hirofumi Hamada, Isao Date
JOURNAL OF GENE MEDICINE, Apr. 2008, JOHN WILEY & SONS LTD, English
Apr. 2008 - Apr. 2008

前立腺癌遺伝子療法の標的遺伝子の探索(EXPLORATION OF TARGET MOLECULES FOR PROSTATE CANCER GENE THERAPY)　　　　　　　　　　　　　　　
中村 公則, 加藤 和則, 鈴木 一弘, 塚本 泰司, 濱田 洋文
日本癌学会総会記事, Aug. 2007, 日本癌学会, English
Aug. 2007 - Aug. 2007

スーパー標的抗体によって認識される新規メラノーマ抗原IL-13受容体α2(Super-targeting antibody NS-66 recognizes a novel tumor antigen interleukin-13 receptor alpha 2 on human melamoma)　　　　　　　　　　　　　　　
桜木 直也, 中村 公則, 加藤 和則, 濱田 洋文
日本癌学会総会記事, Aug. 2007, 日本癌学会, English
Aug. 2007 - Aug. 2007

Superoxide and metastasis　　　　　　　　　　　　　　　
Y. Niitsu, K. Kuribayashi, K. Nakamura, M. Tanaka Araki, T. Sato, R. Takimoto, T. Matsunaga, T. Takayama, J. Kato
CLINICAL & EXPERIMENTAL METASTASIS, 2007, SPRINGER, English
2007 - 2007

Na,K-ATPase beta 1-Mediated Selective Gene Transfer into Neurons.　　　　　　　　　　　　　　　
Keiji Ishii, Kiminori Nakamura, Satoshi Kawaguchi, Rong Li, Sachie Hirai, Naoya Sakuragi, Takuro Wada, Kazunori Kato, Toshihiko Yamashita, Hirofumi Hamada
MOLECULAR THERAPY, May 2006, NATURE PUBLISHING GROUP, English
May 2006 - May 2006

PAP2a-targeted selective gene therapy for pancreatic, prostate, and lung cancers　　　　　　　　　　　　　　　
Kiminori Nakamura, Kazunori Kato, Hirofumi Hamada
JOURNAL OF GENE MEDICINE, Mar. 2006, JOHN WILEY & SONS LTD, English
Mar. 2006 - Mar. 2006

Efficient and selective gene delivery of a fiber-modified adenovirus vector to human myeloma with anti-CD38 antibody　　　　　　　　　　　　　　　
K Kato, Y Masuta, K Tomihara, K Nakamura, H Hamada
JOURNAL OF GENE MEDICINE, Mar. 2006, JOHN WILEY & SONS LTD, English
Mar. 2006 - Mar. 2006

ErbB2-targeted selective cancer gene therapy through FZ33 fiber-modified adenoviral vectors　　　　　　　　　　　　　　　
Kiminori Nakamura, Rong Li, Sachie Hirai, Kazunori Kato, Takashi Masuko, Kazunari K. Yokoyama, Hirofumi Hamada
JOURNAL OF GENE MEDICINE, Mar. 2006, JOHN WILEY & SONS LTD, English
Mar. 2006 - Mar. 2006

Non-cleavable cell surface mutants of CD40 ligand induce immune response and prevent systemic inflammatory reaction　　　　　　　　　　　　　　　
K Kato, Y Masuta, K Tornihara, K Nakamura, H Hamada
JOURNAL OF GENE MEDICINE, Mar. 2006, JOHN WILEY & SONS LTD, English
Mar. 2006 - Mar. 2006

Anti-tumor effect against human carcinoma cells by dendritic cells transfected with CD40 ligand　　　　　　　　　　　　　　　
K Tomihara, K Kato, Y Masuta, K Nakamura, H Hiratsuka, H Hamada
JOURNAL OF GENE MEDICINE, Mar. 2006, JOHN WILEY & SONS LTD, English
Mar. 2006 - Mar. 2006

各種IFNを用いた扁平上皮癌細胞に対する形質変化とアポトーシスの誘導　　　　　　　　　　　　　　　
冨原圭, 加藤和則, 中村公則, 出張裕也, 濱田洋文, 平塚博義
日本癌学会学術総会記事, 2006
2006 - 2006

The Journal of Gene Medicine Japanese Society of Gene Therapy Young Investigator Award 2005 - Kazuhiko Kurozumi, Department of Neurological Surgery, Ohio State University Medical Center, USA
K Kurozumi, K Nakamura, T Ichikawa, T Tamiya, Y Ito, O Honmou, K Houkin, H Hamada, Date, I
JOURNAL OF GENE MEDICINE, Dec. 2005, JOHN WILEY & SONS LTD, English
Dec. 2005 - Dec. 2005

Wnt3 augments adhesion mediated drug resistance of myeloma cells via Wnt/RhoA pathway.　　　　　　　　　　　　　　　
H Chiba, M Kobune, K Kato, K Nakamura, Y Kawano, R Takimoto, T Matsunaga, J Kato, Y Niitsu, H Hamada
BLOOD, Nov. 2005, AMER SOC HEMATOLOGY, English
Nov. 2005 - Nov. 2005

ヒト樹状細胞に対するCD40リガンド遺伝子導入による抗腫瘍効果の検討　　　　　　　　　　　　　　　
冨原 圭, 加藤 和則, 増田 ゆかり, 中村 公則, 野口 誠, 平塚 博義, 濱田 洋文
日本癌学会総会記事, Sep. 2005, 日本癌学会, Japanese
Sep. 2005 - Sep. 2005

抗CD38抗体とファイバー変異型アデノウイルスを用いたヒト骨髄腫細胞への標的化遺伝子導入　　　　　　　　　　　　　　　
増田 ゆかり, 加藤 和則, 冨原 圭, 中村 公則, 濱田 洋文
日本癌学会総会記事, Sep. 2005, 日本癌学会, Japanese
Sep. 2005 - Sep. 2005

Wnt3はnon-canonical経路を介して多発性骨髄腫の抗癌剤耐性を増強させる　　　　　　　　　　　　　　　
千葉 大樹, 小船 雅義, 河野 豊, 中村 公則, 加藤 和則, 瀧本 理修, 松永 卓也, 加藤 淳二, 濱田 洋文, 新津 洋司郎
日本癌学会総会記事, Sep. 2005, 日本癌学会, Japanese
Sep. 2005 - Sep. 2005

Wnt3/Rho経路は多発性骨髄腫における骨髄間質依存性の抗癌剤耐性を惹起する分子機構の一つである　　　　　　　　　　　　　　　
千葉 大樹, 小船 雅義, 河野 豊, 中村 公則, 加藤 和則, 瀧本 理修, 松永 卓也, 加藤 淳二, 濱田 洋文, 新津 洋司郎
日本血液学会・日本臨床血液学会総会プログラム・抄録集, Sep. 2005, 日本臨床血液学会, Japanese
Sep. 2005 - Sep. 2005

Gene-modified mesenchymal stem cells (MSCS) as a therapeutic tool for malignant brain neoplasms　　　　　　　　　　　　　　　
H Hamada, K Nakamura, K Kato
CANCER GENE THERAPY, Dec. 2004, NATURE PUBLISHING GROUP, English
Dec. 2004 - Dec. 2004

Selective and efficient gene delivery of CD40-ligand by a fiber-modified adenovirus vector with specific antibody to human leukemia and myeloma　　　　　　　　　　　　　　　
K Kato, S Hirai, Y Masuta, A Kuroishi, K Nakamura, H Hamada
BLOOD, Nov. 2004, AMER SOC HEMATOLOGY, English
Nov. 2004 - Nov. 2004

Sendai virus vector can efficiently introduce transgene into cardiomyocytes in vitro and in vivo　　　　　　　　　　　　　　　
Y Honma, Y Ito, H Dehari, M Kobune, K Nakamura, J Huang, T Uzuka, T Kobayashi, M Morikawa, M Inoue, M Hasegawa, N Tohse, Y Niitsu, T Abe, H Hamada
GENE THERAPY, Oct. 2004, NATURE PUBLISHING GROUP, English
Oct. 2004 - Oct. 2004

α-GalactosylceramideとアデノIL-2遺伝子治療の併用による抗腫瘍効果および抗転移効果増強の検討　　　　　　　　　　　　　　　
西堀 佳樹, 古川 勝久, 加藤 和則, 田中 真樹, 岡本 哲朗, 竹内 直子, 萩原 誠也, 栗林 景晶, 中村 公則, 新津 洋司郎
基盤的癌免疫研究会総会抄録, Jul. 2004, 日本がん免疫学会, Japanese
Jul. 2004 - Jul. 2004

BDNF gene-modified mesenchymal stem cells promote functional recovery and reduce infarct size in the rat middle cerebral artery occlusion model (vol 9, pg 189, 2004)
K Kurozumi, K Nakamura, T Tamiya, Y Kawano, M Kobune, S Hirai, H Uchida, K Sasaki, Y Ito, K Kato, O Honmou, K Houkin, Date, I, H Hamada
MOLECULAR THERAPY, May 2004, ACADEMIC PRESS INC ELSEVIER SCIENCE, English
May 2004 - May 2004

ヒト骨髄間葉系幹細胞を用いたヒト肝細胞への分化誘導　　　　　　　　　　　　　　　
荒木 啓伸, 佐藤 康史, 加藤 淳二, 中村 公則, 河野 豊, 佐藤 勉, 宮西 浩嗣, 高橋 稔, 濱田 洋文, 新津 洋司郎
肝臓, Apr. 2004, (一社)日本肝臓学会, Japanese
Apr. 2004 - Apr. 2004

Indian hedgehog gene transfer augments hematopoietic support of human stromal cells including NOD/SCID-repopulating cells.　　　　　　　　　　　　　　　
M Kobune, Y Ito, Y Kawano, K Sasaki, H Uchida, K Nakamura, H Dehari, H Chiba, R Takimoto, T Matsunaga, T Terui, J Kato, H Hamada, Y Niitsu
BLOOD, Nov. 2003, AMER SOC HEMATOLOGY, English
Nov. 2003 - Nov. 2003

Wnt3 differentially regulates growth and hematopoietic support in mesenchymal and stromal cells.　　　　　　　　　　　　　　　
H Chiba, M Kobune, Y Ito, Y Kawano, K Sasaki, K Nakamura, H Dehari, T Matsunaga, J Kato, H Hamada, Y Niitsu
BLOOD, Nov. 2003, AMER SOC HEMATOLOGY, English
Nov. 2003 - Nov. 2003

ヒト・ストローマ及び間葉系幹細胞におけるモルフォーゲン遺伝子の発現を応用した造血幹細胞増幅の試み
小船 雅義, 千葉 大樹, 河野 豊, 伊藤 克礼, 中村 公則, 出張 裕也, 松永 卓也, 加藤 淳二, 濱田 洋文, 新津 洋司郎
炎症・再生, Nov. 2003, (一社)日本炎症・再生医学会, Japanese
Nov. 2003 - Nov. 2003

間葉系幹細胞(MSC)を用いた浸潤性グリオーマ遺伝子治療の開発　　　　　　　　　　　　　　　
中村 公則, 伊藤 克礼, 河野 豊, 黒住 和彦, 佐々木 勝則, 備前 明子, 本望 修, 宝金 清博, 濱田 洋文
日本癌学会総会記事, Aug. 2003, 日本癌学会, Japanese
Aug. 2003 - Aug. 2003

不死化ヒト・ストローマ及び間葉系幹細胞におけるWnt遺伝子の発現とその造血支持能に対する効果　　　　　　　　　　　　　　　
千葉 大樹, 小船 雅義, 河野 豊, 伊藤 克礼, 中村 公則, 出張 裕也, 内田 宏昭, 松永 卓也, 加藤 淳二, 濱田 洋文, 新津 洋司郎
臨床血液, Aug. 2003, (一社)日本血液学会-東京事務局, Japanese
Aug. 2003 - Aug. 2003

テロメレース(TERT)遺伝子導入・間葉系幹細胞(MSC)のcobblestone area(CA)支持細胞への分化　　　　　　　　　　　　　　　
小船 雅義, 河野 豊, 伊藤 克礼, 千葉 大樹, 中村 公則, 佐々木 勝則, 津田 肇, 出張 裕也, 内田 宏昭, 松永 卓也, 加藤 淳二, 新津 洋司郎, 濱田 洋文
臨床血液, Aug. 2003, (一社)日本血液学会-東京事務局, Japanese
Aug. 2003 - Aug. 2003

Adenoviral Bcl-xL gene trasfer reduces the infarct size and preserves the cardiac function after ischemia and reperfusion in the rat heart　　　　　　　　　　　　　　　
JH Huang, Y Ito, M Morikawa, M Kobune, H Uchida, K Nakamura, H Dehari, K Takahashi, T Abe, H Hamada
MOLECULAR THERAPY, May 2003, ACADEMIC PRESS INC ELSEVIER SCIENCE, English
May 2003 - May 2003

Human stromal cells transfected with TERT (Telomerase catalytic subunit) gene supports proliferation of SRCs (Scid repopulating cells).　　　　　　　　　　　　　　　
Y Kawano, M Kobune, M Yamaguchi, K Nakamura, Y Ito, T Matsunaga, H Chiba, S Takahashi, K Sasaki, K Kato, J Kato, H Azuma, H Ikeda, Y Niitsu, H Hamada
BLOOD, Nov. 2002, AMER SOC HEMATOLOGY, English
Nov. 2002 - Nov. 2002

Human stromal cells transfected with TERT (telomerasae catalytic subunit) gene supports proliferation of hematopoietic progenitor cells.　　　　　　　　　　　　　　　
Y Kawano, M Kobune, M Yamaguchi, K Nakamura, Y Ito, K Sasaki, T Matsunaga, S Sakamaki, J Kato, S Hirai, K Ikebuchi, Y Niitsu, H Hamada
BLOOD, Nov. 2001, AMER SOC HEMATOLOGY, English
Nov. 2001 - Nov. 2001

口腔扁平上皮癌細胞SASはHGF/SFを自己分泌し浸潤能を促進する
奥村 一彦, 萩野 司, 中村 公則, 田中 真樹, 金澤 正昭
千葉医学雑誌, Apr. 2000, 千葉医学会, Japanese
Apr. 2000 - Apr. 2000

TNFのアポトーシスシグナルにおけるcaspaseとoxygen free radical(OFR)の関連　　　　　　　　　　　　　　　
荻野 司, 奥村 一彦, 中村 公則, 茂尾 公晴, 山内 尚文, 佐藤 勉, 井上 諭, 田中 真樹, 新津 洋司郎, 金澤 正昭
日本口腔外科学会雑誌, Dec. 1999, (公社)日本口腔外科学会, Japanese
Dec. 1999 - Dec. 1999

浸潤,転移マーカーとしての細胞内SOD
中村 公則, 田中 真樹, 萩野 司, 奥村 一彦, 金澤 正昭
第53回日本口腔科学会総会・学術大会, Nov. 1999, (NPO)日本口腔科学会, Japanese
Nov. 1999 - Nov. 1999

高浸潤性舌扁平上皮癌細胞株SAS-H1の血清刺激によるPI3K活性化を介した細胞接着と細胞運動の検討
奥村 一彦, 小西 亮, 山下 知巳, 小村 健, 田中 真樹, 萩野 司, 中村 公則, 金澤 正昭
日本口腔外科学会雑誌, Nov. 1999, (公社)日本口腔外科学会, Japanese
Nov. 1999 - Nov. 1999, 浸潤性の高い口腔扁平上皮癌細胞は,接着や細胞運動性のシグナルとして脂質キナーゼであるPI3Kが重要な役割を担っており,PI3Kの活性化を介して接着斑におけるFAKのチロシンリン酸化を亢進することで細胞接着性を発現して,引き続いて生じる細胞運動を制御していると推察された

Superoxideによるマウスマクロファージ細胞株J774.1の運動能亢進はPKCを介する
中村 公則, 田中 真樹, 萩野 司, 奥村 一彦, 金澤 正昭
日本口腔科学会雑誌, Jan. 1999, (NPO)日本口腔科学会, Japanese
Jan. 1999 - Jan. 1999

細胞内TNFは口腔癌細胞のTNFアポトーシスシグナルに対し抵抗性因子として働いている　　　　　　　　　　　　　　　
荻野 司, 奥村 一彦, 中村 公則, 田中 真樹, 金澤 正昭
日本口腔外科学会雑誌, Dec. 1998, (公社)日本口腔外科学会, Japanese
Dec. 1998 - Dec. 1998

血清刺激による舌扁平上皮癌細胞SASの運動促進シグナルはPI3-K活性化を介している
奥村 一彦, 田中 真樹, 中村 公則, 萩野 司, 金澤 正昭
日本口腔科学会雑誌, Dec. 1998, (NPO)日本口腔科学会, Japanese
Dec. 1998 - Dec. 1998

舌扁平上皮癌SASのPI13 Kinaseを介するFAKのチロシンリン酸化と運動促進
奥村 一彦, 中村 公則, 田中 真樹, 荻野 司, 金澤 正昭
第955回千葉医学会例会・第18回歯科口腔外科例会, Aug. 1998, 千葉医学会, Japanese
Aug. 1998 - Aug. 1998

Superoxideによるマウス・マクロファージ細胞株J774.1の運動能亢進はPKCを介する
中村 公則, 田中 真樹, 萩野 司, 奥村 一彦, 金澤 正昭
東日本歯学会第16回学術大会（平成10年度総会）, Jun. 1998, 北海道医療大学歯学会, Japanese
Jun. 1998 - Jun. 1998

Jun. 2024
日本公衆衛生学会　　　　　　　　　　　　　　　

母乳オリゴ糖の腸管上皮幹細胞ニッシェを介した腸内環境発達メカニズムの解明　　　　　　　　　　　　　　　
Grants-in-Aid for Scientific Research Grant-in-Aid for Challenging Research (Exploratory)
Jun. 2022 - Mar. 2024
中村 公則
Japan Society for the Promotion of Science, Grant-in-Aid for Challenging Research (Exploratory), Hokkaido University, 22K19120

PHRを活用した機械学習モデルによる心血管病の重症化予防を目指した研究
科学研究費助成事業 基盤研究(C)
Apr. 2021 - Mar. 2024
横田 卓, 中岡 慎治, 中村 公則
わが国は超高齢社会を迎え、心血管病の患者数は増加の一途を辿っており、早急に患者本人が主体的にセルフモニタリングを行い疾病予防に取り組む「患者中心の医療 (patient-centered care)」 を実現する必要に迫られている。心血管病の予防・治療の基本は食事・運動をはじめとする生活習慣の是正であるが、在宅で取得可能なパーソナル・ヘルス・レコード (PHR) の活用が必要不可欠である。さらにCOVID-19感染拡大をきっかけにオンライン診療が広く推奨されるようになり、とりわけ情報通信技術 (ICT) を活用したPHRのニーズが高まっている。そこで我々は、在宅で取得するPHRを活用し適切なセルフケアの実践を促すスマートフォン対応セルフケアサポートアプリを開発した。本研究の目的は、このアプリで収集する血圧・体重・体脂肪率・体温・酸素飽和度・塩分摂取量・身体活動量・睡眠時間などのバイタルサインや食事・運動内容、さらには便を用いた腸内フローラ解析データなどの多様なPHRを活用し、機械学習モデルを用いて、心血管病の重症化予測を行うとともに重症化予防のための個々に最適な食事・運動療法を提案することである。
臨床試験『スマートフォンアプリを活用した統合型高血圧セルフケアサポートシステムの有効性の検証 (AppCare-HT Study)』については、2022年3月までに目標症例数 (360名) に達したため、募集を終了し、現在12か月間のフォローアップを実施中である。また、心不全患者を対象にした臨床試験についても研究実施中で、順次データ解析を進めている。
日本学術振興会, 基盤研究(C), 北海道大学, Coinvestigator, 21K08120

Paneth細胞が担う腸内細菌叢の形成からみた疾患リスク上昇メカニズムの理解
科学研究費助成事業 基盤研究(B)
Apr. 2020 - Mar. 2023
中村 公則
本研究は、胎児期から乳幼児期における腸内細菌叢制御に関与する因子であるαディフェンシンを分泌するPaneth細胞の発達異常が、腸内細菌叢形成の破綻を誘導し疾患リスク上昇に関与するとの仮説を立て、そのメカニズムを栄養制御モデルマウスや腸内細菌叢破綻モデルを用いて細胞・分子レベルで証明し、Paneth細胞機能の修復による腸内環境制御機構の正常化を標的とした疾患予防・治療戦略を提案することを目的とする。2021年度は、高脂肪食を摂取した母親由来の子マウス群で示されたαディフェンシン低下に伴う腸内細菌叢の破綻が、αディフェンシン低下そのものに起因するのかを明確にするために、遺伝子的にαディフェンシンを低下させた母親マウス（αDLowM）より生まれた子供（αDLowM-C）のαディフェンシン分泌量測定と腸内細菌叢解析および体重測定を行った。αDLowMの腸内細菌叢は、αディフェンシン正常母親マウス（αDNorM）と比較してβ多様性において異なる分布を示し、腸内細菌叢の破綻（dysbiosis）が誘導されていた。αDLowM-Cのαディフェンシン分泌量は、αDNorMから生まれた子（αDNorM-C）と比較して著しく低下していた。また、αDLowM-Cの腸内細菌叢はαDNorM-Cと比較してβ多様性において異なる分布を示すdysbiosisが誘導されていた。αDLowM-Cの体重は6週齢おいてαDNorM-Cと比較して低かった。以上より、母親のαディフェンシン低下による腸内細菌叢破綻は、子のαディフェンシンを低下させdysbiosiを誘導することが示され、さらに子の低体重誘導に関与する可能性を示した。また、Paneth細胞の顆粒分泌機能評価可能なエンテロイド生体外可視化ライブイメージング解析法により、母親のαディフェンシン分泌量を増加させる食成分の候補が複数抽出された。
日本学術振興会, 基盤研究(B), 北海道大学, Principal investigator, 20H04098

Elucidation of homeostatic mechanism via intestinal environment regulated by oral bacteria
Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)
01 Apr. 2017 - 31 Mar. 2020
Nakamura Kiminori
The purpose of this study was to elucidate the mechanism that commensal bacteria including oral bacteria and pathogenic bacteria are involved in the maintenance of intestinal homeostasis via interaction with Paneth cells. In this study, a novel ex vivo evaluation system to visualize and quantify Paneth cell granule secretion was established by microinjection method of bacteria into the lumen of enteroids, three-dimensional cultures of small intestinal epithelial cells. Paneth cells secreted granules immediately when live non-commensal bacterium S. Typhimurium or commensal bacterium B. bifidum was introduced into the enteroid lumen by microinjection, whereas Paneth cells did not secrete granules when live commensal bacterium L. casei was introduced.
Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (C), Hokkaido University, 17K11661

口腔細菌が規定する腸内環境を介した生体恒常性維持機能の解明　　　　　　　　　　　　　　　
科学研究費補助金(基盤研究(C))
2017 - 2019
中村 公則
文部科学省, Principal investigator, Competitive research funding

Pancreatic-Intestinal Crosstalk: a novel approach to elucidate the tumorigenic process of PDAC
Grants-in-Aid for Scientific Research Grant-in-Aid for Challenging Exploratory Research
01 Apr. 2015 - 31 Mar. 2018
ONO Yusuke
The tumorigenic process of pancreatic ductal carcinoma (PDA) may be closely associated with homeostasis of the intestinal tract, e.g., innate immune system. To elucidate the "Pancreatic-Intestinal Crosstalk" during the tumor initiation, we analyzed the alterations in an intestinal environment using a mouse strain which spontaneously develops acinar-to-ductal metaplasia and pancreatic intraepithelial neoplasias (PanINs), offering a model of the early-stage of the pancreatic tumorigenesis.
16S rRNA gene-based metagenomics assay of stool DNA provided a specific microflora profile during pancreatitis-induced progression from ADM into PanIN. Besides, the morphological study demonstrated the close link between the tumorigenic process in the pancreas and the intestinal tract where Paneth cells may play an essential role.
Japan Society for the Promotion of Science, Grant-in-Aid for Challenging Exploratory Research, Center for Clinical and Biomedical Research, Sapporo Higashi Tokushukai Hospital, 15K14716

Elucidation of the interplay between oral bacteria and intestinal innate immunity using Paneth cells in organoid cultures
Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)
01 Apr. 2014 - 31 Mar. 2017
Nakamura Kiminori
To clarify the relationship between oral bacteria and intestinal epithelia cells in terms of innate immunity, the aim of this study was to establish an evaluation system for intestinal innate immunity focused on Paneth cell α-defensin secretory functions.New analysis method for Paneth cell secretory functions using cultured organoids from mouse small intestine and newly developed sandwich ELISA for α-defensin were established.
These methods will contribute to clarifying links between oral bacteria and intestinal innate immunity.
Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (C), Hokkaido University, Principal investigator, Competitive research funding, 26462831

Paneth cells and their networks as headquarters for clarifying food function
Grants-in-Aid for Scientific Research Grant-in-Aid for Challenging Exploratory Research
01 Apr. 2014 - 31 Mar. 2016
Sakuragi Naoya, NAKAMURA Kiminori
This study was focused on "How Paneth Cell Network is organized" that may work as headquarters in the intestine. To invistigate this possibility, we established high purity and large quantity Paneth cell purification method, and analyzed membrane and secretion related gene expression in Paneth cells. Total 37 genes were identified and classfied into absorption of nutrition, nervous system, metabolism and so on, in addition to innate immunology, renewal and differentiation. These results suggest that Paneth cells may have many important functions and work as headquarters in the intestine.
Japan Society for the Promotion of Science, Grant-in-Aid for Challenging Exploratory Research, Hokkaido University, 26660100

To investigate the clinical application of alpha-defensin in stool in the objective evaluation of radiation enteritis
Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)
01 Apr. 2013 - 31 Mar. 2016
Onodera Shunsuke, Nakamura Kiminori
The purpose of this study was to investigate the clinical application of α-defensin in stool in the objective evaluation of radiation enteritis.As the first step, we experimented on mice and found that the amount of α-defensin significantly decreased in stool of mice irradiated to the abdomen.In addition, a significant negative correlation was observed between the amount of α-defensin and Firmicutes at three days after irradiation.These results suggested that decrease of α-defensin correlated with an altered intestinal flora of the mice irradiated to the abdomen.We could not investigate the clinical application due to insufficient number of patients in this period.
Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (C), 25461899

αディフェンシンによる腸内細菌の統御機構からみた炎症性腸疾患の病因解明と新規治療
科学研究費助成事業 基盤研究(B)
01 Apr. 2011 - 31 Mar. 2014
綾部 時芳, 中村 公則
本研究は、小腸のPaneth細胞が分泌するαディフェンシンの作用から炎症性腸疾患の病因・病態を解明して新規治療を提案することが目的である。本年度は、αディフェンシンと腸内細菌からみた殺菌及び共生メカニズムを、cryptdin およびHD5と腸内細菌との会合から解析した。Acid-Urea PAGE、western blot法、sandwich ELISA等を用いた生化学的・免疫学的解析および殺菌活性測定によって、腸内常在細菌であるLactobacillus、Bifidobacterium等と、非常在菌（病原菌）であるSalmonella、Staphylococcus等でαディフェンシンとの会合状態が異なることを示した。また、クローン病モデルマウスを用いてαディフェンシン異常による腸内共生環境の破壊 (dysbiosis)の可能性について解析した。クローン病モデルマウスのパネト細胞顆粒のcryptdinおよびcryptdin分泌量についてRP-HPLC、Tris-Tricine SDS-PAGE、Acid Urea-PAGE、westen blot法およびsandwich ELISAで解析・測定して、病理病態進展におけるαディフェンシン異常の関与を明らかにした。さらに、小腸絨毛･陰窩におけるcryptdin、MMP7、CD24等の免疫局在を解析し、幹細胞とPaneth細胞が形成するニッチ相互作用の可能性を示した。以上のように、αディフェンシンの病態関与から、クローン病の新規治療法に繋がる重要な成果を得た。本研究で得られた新知見から、αディフェンシン異常によるdysbiosisがクローン病以外にも多くの疾患に寄与すると考え、実際に移植片対宿主病 (GVHD)における病態関与を証明した。
日本学術振興会, 基盤研究(B), 北海道大学, 23390193

Effect of oral bacteria on intestinal innate immunity
Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)
2010 - 2012
NAKAMURA Kiminori
To analyze the interaction of oral bacteria and intestinal epithelia cells, the aim of this study is to establish a intestinal epithelial cell line containing Paneth cells which secrete α -defensins. In conventional monolayer cell culture, intestinal epithelial cells were observed, however, Paneth cells were not identified. Next, organoid culture were performed by using mouse intestinal crypts. It was analyzed whetherobtained organoids were maintaining the function of a Paneth cell.
Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (C), Hokkaido University, 22592029

口腔癌の分子標的化よる新規治療法・診断法の開発
科学研究費助成事業 基盤研究(C)
2008 - 2010
中村 公則
口腔癌の標的化を月指した診断・治療法の開発を目的として、新たな口腔癌細胞に特異的な表面分子の同定するために、ファイバー改変型アデノウイルスAdv-FZ33と癌細胞に対する抗体ライブラリーを用いて、癌細胞に特異的な細胞表面分子をスクリーニング・同定と同時に高性能なモノクローナル抗体の樹立を実施した。抗体ライブラリーの作製:口腔癌細胞(ヒトHSC-2、HSC-3、OSC-70などの混合)でBa1b/cマウスを腹腔へ免役し、P3U1ミエローマ細胞と免疫マウスの脾細胞とをPEG法により細胞融合させ、腫瘍に対する抗体を産生するハイブリドーマ・ライブラリーを作製した。細胞融合後、抗体を含有する培養上清を回収し、以下のスクリーニングを行った。スクリーニングとハイブリドーマ・クローンの樹立:Adv-FZ33を用いて、抗体と腫瘍細胞と架橋することで、遺伝子導入効率が高まるような抗体のスクリーニングを行った。方法:96wellに播種した標的細胞(口腔癌細胞株)に抗体(ハイブリドーマの上清)を反応させる、その後レポーター遺伝子LacZを発現するAx3CAZ3-FZ33を感染させる。24時間後に、Chemiluminescent β-Ga1レポーター遺伝子発現アッセイを行い、LacZ遺伝子産物の発現量を評価する。コントロールに比べて100倍程度、遺伝子導入発現効率が高まっているクローンを選別する。アッセイは3回行い、擬陽性のクローンは除いた。単一のハイブリドーマから単一の抗体産生クローンを樹立するため、96wellを用いたハイブリドーマ細胞の限界希釈クローニングを行った。結果、Z33-Advを介した遺伝子導入が高効率なモノクローナル抗体を12種類樹立する事が出来た。今後、得られた抗体の抗原同定を行って行く。
日本学術振興会, 基盤研究(C), 札幌医科大学, 20592364

Selective targeted drug and gene delivery for cancer treatment
Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research on Priority Areas
2005 - 2009
HAMADA Hirohumi, KATO Kazunori, NAKAMURA Kiminori, HAMA Susumu, YAMAGUCHI Miki
In order to systematically search for the target molecules for cancer gene therapy, we generated a fiber-modified recombinant adenovirus, Adv-FZ33, which contains a Z33 domain with a high affinity for immunoglobulin Fc. By screening with Adv-FZ33, we established a large number of high affinity targeting antibodies (Ab), and identified their target antigen (Ag) molecules, e.g., a panel of 60 Ag species. During these efforts, we also established a unique method (EZiTox) to generate immunotoxins (iTox), which consists of the targeting Ab conjugated with ribosome-inactivating enzyme toxins. EZiTox method will be a strong screening method to find a powerful combination of Ag/Ab for cancer iTox-chemotherapy.
Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research on Priority Areas, Sapporo Medical University, 17016059

腫瘍の特異的標的化を目指した遺伝子治療法の開発
科学研究費助成事業 特定領域研究
2000 - 2004
濱田 洋文, 加藤 和則, 中村 公則, 本望 修, 伊藤 克礼, 佐々木 勝則
腫瘍に対する選択的標的化の候補分子を探索するために、抗体のFcドメインに結合するProtein AのZ33モチーフをAd5ファイバーのHIループに持つAdv-FZ33アデノウイルスを作成した。CARをほとんど発現しないヒト膵癌細胞AsPc1やヒトメラノーマ細胞A375に対する遺伝子導入効率をEGFPないしb-gal遺伝子発現で測定した。AsPc1やA375に発現する表面分子(CD29、CD54など)に対する抗体を付着させたAdv-FZ33による遺伝子導入・遺伝子発現は、コントロール(抗体の非存在下またはコントロールIgG併用でのAdv-FZ33、ならびに野生型Ad5ファイバーAdv-Fwtのウイルス)による遺伝子導入・発現の数十倍に増強できた。また、ErbB2を高発現するヒト卵巣癌細胞(SK-OV3など)への遺伝子導入は、ErbB2抗体の併用により、選択的に著明に(EGFP遺伝子導入細胞%で、5%から90%へ)増強できた。腫瘍細胞とZ33アデノウイルスとを架橋することによって遺伝子導入効率が高まるモノクローナル抗体をスクリーニングすることにより、腫瘍細胞に対して標的化の可能な表面分子と抗体の組み合わせの探索を開始している。先行しているヒト膵癌を標的化できる新規抗体作製のプロジェクトでは、すでに4種類の抗体産生ハイブリドーマが樹立されている。このうちの一つクローンA^*によって得られるモノクローナル抗体は、AdvFZ33アデノウイルスの膵癌細胞AsPc1への遺伝子導入効率を、非常に強く(200倍)増強し、有望である。
日本学術振興会, 特定領域研究, 札幌医科大学, 12217123

口腔癌の分子標的化よる新規治療法・診断法の開発　　　　　　　　　　　　　　　
科学研究費補助金(基盤研究(C))
中村 公則
文部科学省, Principal investigator, Competitive research funding

ヒトαディフェンシンHD5を検出する方法及びキット、並びにこれらにおいて用いられる抗体
Patent right, 綾部 時芳, 中村 公則, 国立大学法人北海道大学
特願2020-009553, 23 Jan. 2020
特開2021-117062, 10 Aug. 2021
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Patent right, 森川 琢海, 北村 整一, 鍔田 仁人, 綾部 時芳, 中村 公則, 株式会社東洋新薬
特願2015-166850, 26 Aug. 2015
特開2017-043554, 02 Mar. 2017
特許第6607380号, 01 Nov. 2019
201903019006558815

抗菌性ペプチドの分泌促進剤
Patent right, 石川 純嗣, 綾部 時芳, 中村 公則, 株式会社ファンケル
特願2013-234237, 12 Nov. 2013
特開2015-093852, 18 May 2015
特許第6209062号, 15 Sep. 2017
201703015437482832

腸管線維症処置剤
Patent right, 綾部 時芳, 中村 公則, 味呑 憲二郎, 田中 康進, 日東電工株式会社
特願2012-252167, 16 Nov. 2012
特開2013-126975, 27 Jun. 2013
特許第5873419号, 22 Jan. 2016
201603002689572050

抗微生物物質産生・分泌促進剤
Patent right, 綾部 時芳, 中村 公則, 吉成 篤四郎, 石田 真己, 国立大学法人北海道大学, 株式会社スリービー
特願2011-045604, 02 Mar. 2011
特開2012-180329, 20 Sep. 2012
特許第5088911号, 21 Sep. 2012
201303081047870680

パネト細胞群の製造方法、パネト細胞の抗微生物物質の分泌を促進する対象のスクリーニング方法およびパネト細胞からの分泌物の製造方法
Patent right, 綾部 時芳, 坂井 直樹, 中村 公則, 国立大学法人北海道大学
特願2009-230904, 02 Oct. 2009
特開2011-078318, 21 Apr. 2011
201103050366618393

IL13Ra2に対する抗体およびこれを含む診断・治療薬
Patent right, 濱田 洋文, 加藤 和則, 中村 公則, 北海道公立大学法人 札幌医科大学
特願2007-147478, 01 Jun. 2007
特開2010-190572, 02 Sep. 2010
201003007136997115

PAP2aに対する抗体ならびにその診断的および治療的使用
Patent right, 濱田 洋文, 中村 公則, 加藤 和則, 北海道公立大学法人 札幌医科大学
特願2007-516364, 17 May 2006
特開2008-163029, 17 Jul. 2008
WO2006-123829, 23 Nov. 2006
特許第4097041号, 21 Mar. 2008
201103007632735411

不死化間葉系細胞及びその利用
Patent right, 濱田 洋文, 河野 豊, 中村 公則, 小船 雅義, 本望 修, 田之岡 篤, 岡 真一, 佐々木 勝則, 津田 肇, 伊藤 克礼, 加藤 淳二, 松永 卓也, 新津 洋司郎, 株式会社レノメディクス研究所, 帝国臓器製薬株式会社, 三井住友海上ケアネット株式会社, 株式会社日立製作所
JP2002011389, 31 Oct. 2002
WO2003-038076, 08 May 2003
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パネト細胞群の製造方法、パネト細胞の抗微生物物質の分泌を促進する対象のスクリーニング方法　　　　　　　　　　　　　　　
Patent right

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