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Haga Sanae

Faculty of Medicine　Social Medicine　Social MedicinePostdoctoral Fellow

Researcher basic information

■ Degree
  • 博士（医学）, 北海道大学
■ URL
researchmap URLホームページURL■ Various IDs
J-Global ID■ Research Keywords and Fields
Research Keyword
  • 脂肪肝
  • 肝再生
  • 肝傷害
  • 生体イメージング
  • 光プローブ
  • 細胞死
  • 分子制御
  • ストレス
  • 細胞情報伝達
  • バイオイメージング
  • マウス
  • 光イメージング
  • 癌細胞機能解析
Research Field
  • Life Science, Molecular biology
  • Life Science, Digestive surgery
■ Educational Organization

Research activity information

■ Papers
  • In vivo bioluminescence imaging revealed the change of the time window of BDNF expression in the brain elicited by a single bout of exercise following repeated exercise
    Ryo Ikegami; Takahiro Inoue; Yasuyuki Takamatsu; Taichi Nishio; Mamoru Fukuchi; Sanae Haga; Michitaka Ozaki; Hiroshi Maejima
    Neuroscience Letters, 137830, 137830, Elsevier BV, May 2024
    Scientific journal
  • Temporal dynamics of brain BDNF expression following a single bout of exercise: A bioluminescence imaging study.
    Takahiro Inoue; Ryo Ikegami; Yasuyuki Takamatsu; Mamoru Fukuchi; Sanae Haga; Michitaka Ozaki; Hiroshi Maejima
    Neuroscience letters, 799, 137120, 137120, 16 Mar. 2023, [International Magazine]
    English, Scientific journal, Physical exercise increases brain-derived neurotrophic factor (BDNF) expression in the brain. However, the absence of non-invasive and repetitive monitoring of BDNF expression in the brains of living animals has limited the understanding of how BDNF expression changes after exercise. This study aimed to elucidate the temporal dynamics of BDNF expression in the brain after a single bout of exercise, using in vivo bioluminescence imaging. This study included Bdnf-Luc mice with a firefly Luciferase gene inserted at the translation start site of the mouse Bdnf gene. BDNF expression was evaluated based on the luminescence signal of the luciferase substrate administered to mice. Bioluminescence imaging was performed at 0, 1, 3, 6, 12, and 24 h after treadmill exercise (15 m/min for 1 h). Compared to the sedentary condition of each mouse, the luminescence signal increased by approximately 60 % between 1 and 3 h after exercise. The luminescence signal remained slightly increased by approximately 20 % even 6-24 h after exercise. This study is the first to demonstrate exercise-enhanced BDNF expression in the brains of living animals. These results provide evidence that a single bout of exercise transiently increases BDNF expression in the brain within a limited time window.
  • Analysis of the Anticipatory Behavior Formation Mechanism Induced by Methamphetamine Using a Single Hair
    Riku Sato; Megumi Kanai; Yukina Yoshida; Shiori Fukushima; Masahiro Nogami; Takeshi Yamaguchi; Norio Iijima; Kenneth Sutherland; Sanae Haga; Michitaka Ozaki; Kazuko Hamada; Toshiyuki Hamada
    Cells, 12, 4, 654, 654, MDPI AG, 17 Feb. 2023
    Scientific journal, While the suprachiasmatic nucleus (SCN) coordinates many daily rhythms, some circadian patterns of expression are controlled by SCN-independent systems. These include responses to daily methamphetamine (MAP) injections. Scheduled daily injections of MAP resulted in anticipatory activity, with an increase in locomotor activity immediately prior to the time of injection. The MAP-induced anticipatory behavior is associated with the induction and a phase advance in the expression rhythm of the clock gene Period1 (Per1). However, this unique formation mechanism of MAP-induced anticipatory behavior is not well understood. We recently developed a micro-photomultiplier tube (micro-PMT) system to detect a small amount of Per1 expression. In the present study, we used this system to measure the formation kinetics of MAP-induced anticipatory activity in a single whisker hair to reveal the underlying mechanism. Our results suggest that whisker hairs respond to daily MAP administration, and that Per1 expression is affected. We also found that elevated Per1 expression in a single whisker hair is associated with the occurrence of anticipatory behavior rhythm. The present results suggest that elevated Per1 expression in hairs might be a marker of anticipatory behavior formation.
  • The usefulness of measuring n-butyric acid concentration as a new indicator of blood decomposition in forensic autopsy.
    Kotaro Matoba; Manabu Murakami; Emi Fujita; Shigeki Jin; Ryosuke Ogasawara; Tomoko Matoba; Akiko Takeuchi; Sanae Haga; Michitaka Ozaki; Hideki Hyodoh
    Legal medicine (Tokyo, Japan), 57, 102071, 102071, 15 Apr. 2022, [International Magazine]
    English, Scientific journal, In forensic medicine, although various alcohols have been reported as indicators of decomposition in collected blood, no studies have examined short-chain fatty acids as indicators. In this study, the blood n-butyric acid concentration was quantified, and the association between n-butyric acid and decomposition was investigated to determine whether the detection of n-butyric acid could be a new indicator of decomposition. Among the forensic autopsies performed from 2016 to 2018 in our laboratory, the cases were divided into decomposed (n = 20) and non-decomposed (n = 20) groups based on macroscopic findings. Blood samples collected at the time of autopsy were derivatized with 3-nitrophenylhydrazine hydrochloride after solid-phase extraction. The n-butyric acid concentration was measured using liquid chromatography-tandem mass spectrometry. In addition, ethanol and n-propanol were measured using a gas chromatography-flame ionization detector. There was a significant difference (p < 0.01) in the concentrations of n-butyric acid between the decomposed and non-decomposed groups (0.343 ± 0.259 [0.030-0.973] and 0.003 ± 0.002 [0.001-0.007] mg/mL, respectively). In the decomposed group, n-butyric acid was detected at high concentrations, even in cases where n-propanol was low. These results suggest that n-butyric acid is more likely to be an indicator of blood decomposition than n-propanol.
  • Poly(ADP-ribose) polymerase (PARP) is critically involved in liver ischemia/reperfusion-injury
    S. Haga; A. Kanno; N. Morita; S. Jin; K. Matoba; T. Ozawa; M. Ozaki
    The Journal of Surgical Research, 270, 124, 138, Oct. 2021, [Peer-reviewed]
    English, Scientific journal
  • Period1 gene expression in the olfactory bulb and liver of freely moving streptozotocin-treated diabetic mouse.
    Harumi Kanou; Kouki Nagasawa; Yuki Ishii; Aya Chishima; Juri Hayashi; Sanae Haga; Kenneth Sutherland; Masayori Ishikawa; Michitaka Ozaki; Hiroki Shirato; Kazuko Hamada; Toshiyuki Hamada
    Biochemical and biophysical research communications, 560, 14, 20, 30 Jun. 2021, [International Magazine]
    English, Scientific journal, Clock genes express circadian rhythms in most organs. These rhythms are organized throughout the whole body, regulated by the suprachiasmatic nucleus (SCN) in the brain. Disturbance of these clock gene expression rhythms is a risk factor for diseases such as obesity. In the present study, to explore the role of clock genes in developing diabetes, we examined the effect of streptozotocin (STZ)-induced high glucose on Period1 (Per1) gene expression rhythm in the liver and the olfactory bub (OB) in the brain. We found a drastic increase of Per1 expression in both tissues after STZ injection while blood glucose content was low. After a rapid expression peak, Per1 expression showed no rhythm. Associated with an increase of glucose content, behavior became arrhythmic. Finally, we succeeded in detecting an increase of Per1 expression in mice hair follicles on day 1 after STZ administration, before the onset of symptoms. These results show that elevated Per1 expression by STZ plays an important role in the aggravation of diabetes.
  • Sample preparation method with ultrafiltration for whole blood thiosulfate measurement.
    Shigeki Jin; Manabu Murakami; Kotaro Matoba; Tomoko Matoba; Sanae Haga; Michitaka Ozaki; Akiko Takeuchi; Hideki Hyodoh
    Legal medicine (Tokyo, Japan), 47, 101765, 101765, 23 Jul. 2020, [Peer-reviewed], [International Magazine]
    English, Scientific journal, Quantitative analysis of thiosulfate is useful for diagnosing hydrogen sulfide poisoning. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) enables more rapid and sensitive measurements than previous methodologies. As simple measurements of blood thiosulfate concentration are affected by the blood matrix, blood is used as the solvent to prepare the standard solution for calibration curve generation. Thus, a large amount of blood devoid of thiosulfate is required. We developed a preparation method by incorporating an ultrafiltration step to overcome this limitation and generate a calibration curve using a standard solution prepared with pure water. We used this improved method to investigate the stability of thiosulfate in refrigerated samples. To compare the effects of refrigeration, blood samples were prepared using the following two methods: one sample was treated with a 50-kDa exclusion ultrafiltration membrane and the other was not treated. The samples were stored at 4 °C, and then measured at 0, 3, 6, 24, 48, and 96 h. The incorporation of the ultrafiltration step in the measurement procedure enabled the quantification of thiosulfate, by plotting a calibration curve using a standard of pure water; it did not require a blood standard. Additionally, the reduction in whole blood thiosulfate concentration was within 10% during 2 days of refrigeration. Thus, the need for a large amount of blood to prepare the standard solution was resolved by the ultrafiltration step in test sample preparation. This method is useful to measure thiosulfate concentration and is not hindered by sample refrigeration for a few days.
  • Extracts of bilberry (Vaccinium myrtillus L.) fruits improve liver steatosis and injury in mice by preventing lipid accumulation and cell death.
    Sanae Haga, Yimin; Hikari Yamaki; Shigeki Jin; Tetsuya Sogon; Naoki Morita; Michitaka Ozaki
    Bioscience, Biotechnology, and Biochemistry, 83, 11, 2110, 2120, Oxford University Press (OUP), Jun. 2019, [Peer-reviewed]
    English, Scientific journal, ABSTRACT
    Bilberry has been reported to have anti-oxidant and anti-inflammatory properties. We studied the effect of bilberry (Vaccinium myrtillus L.) fruits extracts (BEs) on the pathogenesis caused by lipid accumulation in fatty liver and non-alcoholic steatohepatitis (NASH). 5 μg/ml of BEs was enough to suppress lipid accumulation in the fatty liver model of the mouse hepatic AML12 cells. BEs increased cell viability and anti-oxidant capacity, presumably by activating (phosphorylating) Akt/STAT3 and inducing MnSOD/catalase. BEs also significantly reduced Rubicon and induced p62/SQSTM1, possibly contributing to reduce cellular lipids (lipophagy). When the mice were fed supplemented with BEs (5% or 10%, w/w), hepatic steatosis, injury, and hypercholesterolemia/hyperglycemia were significantly improved. Furthermore, histological and cytokine studies indicated that BEs possibly suppress hepatic inflammation (hepatitis) and fibrosis. Therefore, BEs improved liver steatosis and injury, and potentially suppress fibrosis by suppressing inflammatory response, which therefore may prevent the progression of fatty liver to NASH.
  • Activation of caspase-3 during Chlamydia trachomatis-induced apoptosis at a late stage.
    Junji Matsuo; Sanae Haga; Kent Hashimoto; Torahiko Okubo; Takeaki Ozawa; Michitaka Ozaki; Hiroyuki Yamaguchi
    Canadian Journal of Microbiology, 65, 2, 135, 143, Feb. 2019, [Peer-reviewed], [International Magazine]
    English, Scientific journal, The obligate intracellular bacterium Chlamydia trachomatis activates the host cell apoptosis pathway at a late stage of its developmental cycle. However, whether caspase-3, which is a key enzyme of apoptosis, is activated in Chlamydia-infected cells remains unknown. Here, we established HEp-2 cells stably expressing cFluc-DEVD, which is a caspase-3 substrate sequence inserted into cyclic firefly luciferase, and then monitored the dynamics of caspase-3 activity in cells infected with Chlamydia. Transfected cells without infection showed a significant increase in luciferase activity due to stimulation with staurosporine, an inducer of apoptosis. Activation was significantly blocked by addition of caspase inhibitor z-VAD-fmk. Furthermore, as expected, Chlamydia infection caused a significant increase in luciferase activation at 36-48 h postinfection with a contrastive decrease at 24 h postinfection, which is already well known. Such activation caused by the infection was much stronger when the amount of bacteria was increased. Thus, caspase-3 activation was accurately monitored by the luciferase activity in HEp-2 cells constitutively expressing the cFluc-DEVD probe. Furthermore, our data showed that C. trachomatis activates caspase-3 in host cells at a late stage of infection.
  • Detection of necroptosis in ligand-mediated and hypoxia-induced injury of hepatocytes using a novel optic probe-detecting receptor-interacting protein (RIP)1/RIP3 binding
    Sanae Haga; Akira Kanno; Takeaki Ozawa; Naoki Morita; Mami Asano; Michitaka Ozaki
    Oncology Research, 26, 3, 503, 513, Cognizant Communication Corporation, 2018, [Peer-reviewed]
    English, Scientific journal
  • Photo-activatable akt probe: A new tool to study the akt-dependent physiopathology of cancer cells
    Sanae Haga; Takeaki Ozawa; Naoki Morita; Mami Asano; Shigeki Jin; Yimin; Michitaka Ozaki
    Oncology Research, 26, 3, 467, 472, Cognizant Communication Corporation, 2018, [Peer-reviewed]
    English, Scientific journal
  • Evaluation and regulation cellular/organ functions by optic technology.
    Michitaka Ozaki; Sanae Haga; Takeaki Ozawa; Naoki Morita; Toshiyuki Hamada
    Organ Biology, 24, 2, 87, 91, The Japan Society for Organ Preservation and Biology, 2017, [Peer-reviewed]
    English, Scientific journal, To develop an effective organ/cell preservation method and to monitor post-transplant graft function continuously and non-invasively, an innovative optic technology to visualize cell/organ function seems to be useful. We have developed some optic probes to visualize regulated cell death (apoptosis, necroptosis, pyroptosis), redox states and cellular stresses, pH and cellular antigens in deeper lesions of the organ. In the hepatic ischemia/reperfusion model of mice, we successfully imaged liver oxidative stress (by redox-sensitive GFP) and apoptosis (by caspase-3 activity) non-invasively and chronologically in a single mouse. We also developed a unique tool to visualize intracellular pH and succeeded in imaging dynamic changes of pH in a mouse posterior limb ischemia/reperfusion model. We are also developing the new devices for tissue/organ imaging. We are trying to monitor the optic signals chronologically and track the lesions in the body by developing light sensor and multiple CCD camera system, which can be used in endoscopic examination and surgical operation. It is still on a way, but this kind of technology will definitely provide a new avenue toward effective and non-invasive surgical therapy in the future.
  • Relevance of FXR-p62/SQSTM1 pathway for survival and protection of mouse hepatocytes and liver, especially with steatosis
    Sanae Haga; Yimin; Michitaka Ozaki
    BMC GASTROENTEROLOGY, 17, 1, 9, Jan. 2017, [Peer-reviewed]
    English, Scientific journal
  • Inflammatory responses increase secretion of MD-1 protein
    Richard Thomas Jennings; Erdenezaya Odkhuu; Akina Nakashima; Naoko Morita; Toshihiko Kobayashi; Ikuko Yamai; Miyako Tanaka; Takayoshi Suganami; Sanae Haga; Michitaka Ozaki; Yasuharu Watanabe; Yoshinori Nagai; Kiyoshi Takatsu; Takane Kikuchi-Ueda; Isao Ichimonji; Yoshihiro Ogawa; Hidekazu Takagi; Tatsuya Yamazaki; Kensuke Miyake; Sachiko Akashi-Takamura
    INTERNATIONAL IMMUNOLOGY, 28, 10, 503, 512, Oct. 2016, [Peer-reviewed]
    English, Scientific journal
  • Development for the measurement of serum thiosulfate using LC-MS/MS in forensic diagnosis of H2S poisoning
    Shigeki Jin; Hideki Hyodoh; Kotaro Matoba; Fei Feng; Akira Hayakawa; Katsuhiro Okuda; Keiko Shimizu; Sanae Haga; Michitaka Ozaki; Koichi Terazawa
    LEGAL MEDICINE, 22, 18, 22, Sep. 2016, [Peer-reviewed]
    English, Scientific journal
  • Long-term ex vivo and in vivo monitoring of tumor progression by using dual luciferases
    Naoki Morita; Sanae Haga; Yoshihiro Ohmiya; Michitaka Ozaki
    ANALYTICAL BIOCHEMISTRY, 497, 24, 26, Mar. 2016, [Peer-reviewed]
    English, Scientific journal
  • A new strategy for organ preservation by p62/SQSTM1
    Ozaki Michitaka; Haga Sanae
    Organ Biology, 23, 2, 168, 172, The Japan Society for Organ Preservation and Biology, 2016
    Japanese, We have been investigating the mechanism of liver regeneration and injury for liver surgery and transplantation. We firstly studied, in normal liver, the central role of IL-6/Jak/STAT3 in post-PH mitotic response and protective mechanism from hepatocyte injury, and the essential role of PDK1/Akt in post-PH cell growth in case where mitotic response is impaired. In fatty liver, reduced expression of p62/SQSTM1 plays a crucial role in post-hepatectomy acute injury and delayed regeneration with enhanced oxidative stress- and death signal-mediated injury. Reduced expression of p62/SQSTM1 lead to FasL/Fas overexpression and suppressed antioxidant genes through Nrf-2 inactivation, which along with the hypo-responsiveness of Akt, caused post-hepatectomy necrotic/apoptotic liver injury and delayed regeneration. Our study importantly suggests the potential role of p62/SQSTM1 in protecting the liver from all kinds of injury, providing pro-survival property to hepatocytes/liver. Here, we report the pivotal roles of p62/SQSTM1 as a key player for cell/organ preservation, and the potential application for liver preservation and transplantation.
  • Mitochondrial delivery of Coenzyme Q(10) via systemic administration using a MITO-Porter prevents ischemia/reperfusion injury in the mouse liver
    Yuma Yamada; Kohei Nakamura; Jiro Abe; Mamoru Hyodo; Sanae Haga; Michitaka Ozaki; Hideyoshi Harashima
    JOURNAL OF CONTROLLED RELEASE, 213, 86, 95, Sep. 2015, [Peer-reviewed]
    English, Scientific journal
  • 虚血再灌流臓器障害に関する基礎研究の進歩 基礎研究・移植再生 光イメージングによる虚血再灌流障害の動的・質的解析
    尾崎 倫孝; 芳賀 早苗; 野田 なつみ; 小澤 岳昌; 森田 直樹
    日本外科学会定期学術集会抄録集, 115回, SY, 6, (一社)日本外科学会, Apr. 2015
    Japanese
  • Growth Arrest and DNA Damage-Inducible 34 Regulates Liver Regeneration in Hepatic Steatosis in Mice
    Yuka Inaba; Tomoko Furutani; Kumi Kimura; Hitoshi Watanabe; Sanae Haga; Yoshiaki Kido; Michihiro Matsumoto; Yasuhiko Yamamoto; Kenichi Harada; Shuichi Kaneko; Seiichi Oyadomari; Michitaka Ozaki; Masato Kasuga; Hiroshi Inoue
    HEPATOLOGY, 61, 4, 1343, 1356, Apr. 2015, [Peer-reviewed]
    English, Scientific journal
  • p62/SQSTM1 Plays a Protective Role in Oxidative Injury of Steatotic Liver in a Mouse Hepatectomy Model
    Sanae Haga; Takeaki Ozawa; Yuma Yamada; Naoki Morita; Izuru Nagashima; Hiroshi Inoue; Yuka Inaba; Natsumi Noda; Riichiro Abe; Kazuo Umezawa; Michitaka Ozaki
    ANTIOXIDANTS & REDOX SIGNALING, 21, 18, 2515, 2530, Dec. 2014, [Peer-reviewed]
    English, Scientific journal
  • "光"を利用した新たな細胞・臓器保存法の開発
    芳賀 早苗; 小澤 岳昌; 野田 なつみ; 尾崎 倫孝
    Organ Biology, 21, 3, 42, 42, (一社)日本臓器保存生物医学会, Oct. 2014
    Japanese
  • 高血糖および脂肪化状態が肝虚血/再灌流傷害に及ぼす影響
    芳賀 早苗; 小澤 岳昌; 森田 直樹; 野田 なつみ; 尾崎 倫孝
    日本生化学会大会プログラム・講演要旨集, 87回, [2P, 408], (公社)日本生化学会, Oct. 2014
    Japanese
  • 細胞・臓器移植における基礎的研究の最前線 光を応用した移植細胞機能・細胞環境のモニタリングと制御の試み
    尾崎 倫孝; 芳賀 早苗; 野田 なつみ; 森田 直樹; 山田 勇磨; 小澤 岳昌
    日本外科学会雑誌, 115, 臨増2, 168, 168, (一社)日本外科学会, Mar. 2014
    Japanese
  • 臓器保存 光学技術を応用した新たな臓器保存法、細胞・臓器移植法の開発
    尾崎 倫孝; 芳賀 早苗; 森田 直樹; 野田 なつみ; 山田 勇馬; 小澤 岳昌
    Organ Biology, 20, 3, 40, 40, (一社)日本臓器保存生物医学会, Oct. 2013
    Japanese
  • Contribution of Toll-Like Receptor 2 to the Innate Response against Staphylococcus aureus Infection in Mice
    Yimin; Masashi Kohanawa; Songji Zhao; Michitaka Ozaki; Sanae Haga; Guangxian Nan; Yuji Kuge; Nagara Tamaki
    PLoS ONE, 8, 9, e74287, 13 Sep. 2013, [Peer-reviewed]
    English, Scientific journal
  • 光応答性ルシフェラーゼによる生きた組織下でのpH時間変化モニタリング法の開発
    服部 満; 芳賀 早苗; 高倉 栄男; 尾崎 倫孝; 小澤 岳昌
    日本分析化学会講演要旨集, 62年会, 42, 42, (公社)日本分析化学会, Aug. 2013
    Japanese
  • Sustained accurate recording of intracellular acidification in living tissues with a photo-controllable bioluminescent protein
    Mitsuru Hattori; Sanae Haga; Hideo Takakura; Michitaka Ozaki; Takeaki Ozawa
    PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 110, 23, 9332, 9337, Jun. 2013, [Peer-reviewed]
    English, Scientific journal
  • A Method for Intravital Monitoring of Human Cells Using a Far-Red Luminescent Probe in Graft-Versus-Host Disease Model Mice
    Hongjiang Qiao; Riichiro Abe; Nao Saito; Yasuyuki Fujita; Inkin Hayashi-Ujiie; Gang Wang; Sanae Haga; Chun Wu; Yoshihiro Ohmiya; Michitaka Ozaki; Hiroshi Shimizu
    JOURNAL OF INVESTIGATIVE DERMATOLOGY, 133, 3, 841, 843, Mar. 2013, [Peer-reviewed]
    English
  • Immunosuppressive effects of DTCM-G, a novel inhibitor of the mTOR downstream signaling pathway
    Susumu Shibasaki; Kenichiro Yamashita; Ryoichi Goto; Kenji Wakayama; Yusuke Tsunetoshi; Masaaki Zaitsu; Rumi Igarashi; Sanae Haga; Michitaka Ozaki; Kazuo Umezawa; Satoru Todo
    Transplantation, 95, 4, 542, 550, 27 Feb. 2013, [Peer-reviewed]
    English, Scientific journal
  • Anoikis Induction and Inhibition of Peritoneal Metastasis of Pancreatic Cancer Cells by a Nuclear Factor-kappa B Inhibitor, (-)-DHMEQ
    Masanori Sato; Kazuaki Nakanishi; Sanae Haga; Masato Fujiyoshi; Motoi Baba; Kazuhiro Mino; Yimin; Haruki Niwa; Hideki Yokoo; Kazuo Umezawa; Yoshihiro Ohmiya; Toshiya Kamiyama; Satoru Todo; Akinobu Taketomi; Michitaka Ozaki
    ONCOLOGY RESEARCH, 21, 6, 333, 343, 2013, [Peer-reviewed]
    English, Scientific journal
  • Successful transplantation of rat hearts subjected to extended cold preservation with a novel preservation solution
    Kenji Wakayama; Moto Fukai; Kenichiro Yamashita; Taichi Kimura; Gentaro Hirokata; Susumu Shibasaki; Daisuke Fukumori; Sanae Haga; Mitsuru Sugawara; Tomomi Suzuki; Masahiko Taniguchi; Tsuyoshi Shimamura; Hiroyuki Furukawa; Michitaka Ozaki; Toshiya Kamiyama; Satoru Todo
    TRANSPLANT INTERNATIONAL, 25, 6, 696, 706, Jun. 2012, [Peer-reviewed]
    English, Scientific journal
  • Dendritic Cells Conditioned With NK026680 Prolong Cardiac Allograft Survival in Mice
    Susumu Shibasaki; Kenichiro Yamashita; Yoshiki Yanagawa; Ryoichi Goto; Kenji Wakayama; Gentaro Hirokata; Yusuke Tsunetoshi; Masaaki Zaitsu; Rumi Igarashi; Sanae Haga; Michitaka Ozaki; Satoru Todo
    TRANSPLANTATION, 93, 12, 1229, 1237, Jun. 2012, [Peer-reviewed]
    English, Scientific journal
  • Bio-imaging of surgical stress: Dynamic analysis of liver oxidative stress and damage
    Morita Naoki; Haga Sanae; Ozawa Takeaki; Remington S. James; Ozaki Michitaka
    LUMINESCENCE, 27, 2, 143, 145, Mar. 2012, [Peer-reviewed]
  • NK026680 inhibits T-cell function in an IL-2-dependent manner and prolongs cardiac allograft survival in rats
    Susumu Shibasaki; Kenichiro Yamashita; Ryoichi Goto; Tetsu Oura; Kenji Wakayama; Gentaro Hirokata; Tomohiro Shibata; Rumi Igarashi; Sanae Haga; Michitaka Ozaki; Satoru Todo
    TRANSPLANT IMMUNOLOGY, 26, 1, 42, 49, Jan. 2012, [Peer-reviewed]
    English, Scientific journal
  • In Vivo Monitoring of Liver Damage Using Caspase-3 Probe
    Michitaka Ozaki; Sanae Haga; Takeaki Ozawa
    THERANOSTICS, 2, 2, 207, 214, 2012, [Peer-reviewed]
    English, Scientific journal
  • 'Collagen vitrigel sheet' as a novel drug delivery bio-material
    S. Haga; S. Haga; T. Takezawa; T. Ozawa; S. J. Remington; N. Morita; M. Ozaki
    IFMBE Proceedings, 37, 1354, 1357, 09 Nov. 2011
  • AGE-ASSOCIATED P66SHC INDUCED REDOX-DEPENDENT LIVER DAMAGE AND IMPAIRED REGENERATION AFTER HEPATECTOMY IN AGED MICE
    Ozaki Michitaka; Haga Sanae; Irani Kaikobad; Morita Naoki; Kaneshima Yoshimi; Ozawa Takeaki
    HEPATOLOGY, 54, 686A, 687A, Oct. 2011, [Peer-reviewed]
  • Inhibition of nuclear factor-kappaB suppresses peritoneal dissemination of gastric cancer by blocking cancer cell adhesion
    Kazuhiro Mino; Michitaka Ozaki; Kazuaki Nakanishi; Sanae Haga; Masanori Sato; Masaya Kina; Masato Takahashi; Norihiko Takahashi; Akihiko Kataoka; Kazuyoshi Yanagihara; Takahiro Ochiya; Toshiya Kamiyama; Kazuo Umezawa; Satoru Todo
    CANCER SCIENCE, 102, 5, 1052, 1058, May 2011, [Peer-reviewed]
    English, Scientific journal
  • Bio-imaging of surgical stresses - Dynamic analyses of liver oxidative stress and damage - Dynamic a
    M. Ozaki; S. Haga; T. Ozawa; N. Morita; Y. Kaneshima; J. Remington
    IFMBE Proceedings, 37, 1094, 1097, 2011
    English, International conference proceedings
  • p66(Shc) has a pivotal function in impaired liver regeneration in aged mice by a redox-dependent mechanism
    Sanae Haga; Naoki Morita; Kaikobad Irani; Masato Fujiyoshi; Tetsuya Ogino; Takeaki Ozawa; Michitaka Ozaki
    LABORATORY INVESTIGATION, 90, 12, 1718, 1726, Dec. 2010, [Peer-reviewed]
    English, Scientific journal
  • [Development of novel cell culture systems utilizing the advantages of collagen vitrigel membrane].
    Toshiaki Takezawa; Maya Fukuda; Winnette McIntosh-Ambrose; Ji-Ae Ko; Jennifer Elisseeff; Sanae Haga; Michitaka Ozaki; Kiyoko Kato; Pi-Chao Wang; Tadashi Uchino; Teruo Nishida
    Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan, 130, 4, 565, 74, Apr. 2010, [Peer-reviewed], [Domestic magazines]
    Japanese, Scientific journal, The white of an egg, rendered opaque by boiling, can be converted into a thin, transparent and rigid material like glass by evaporating the moisture. This phenomenon is known as the vitrification of heat-denatured proteins. We applied vitrification technology to a collagen gel and converted it into a rigid glass-like material. We attempted to rehydrate the glass-like material and succeeded in preparing a novel stable state of collagen gel that was a thin and transparent membrane with excellent gel strength and protein permeability. We called it "collagen vitrigel" because it was produced from the vitrification process of a traditional hydrogel. Further, a framework-embedded collagen vitrigel membrane that can be easily turned inside out with tweezers was prepared by inserting a nylon membrane ring in the collagen sol prior to the gelation, thereby allowing the membrane to function as a removable cell culture substratum. Different types of anchorage-dependent cells could be cultured on both surfaces of the substratum by the manipulation of two-dimensional cultures, and consequently a three-dimensional crosstalk model with paracrine effects from each cell type was reconstructed. Also, the collagen vitrigel membrane containing a bioactive molecule provided a drug delivery system (DDS) with sustainable release. In this review, we summarize the recent progress of applied studies using the collagen vitrigel membrane as follows: a corneal model for eye irritant and permeability tests, a skin model for sensitization test, a renal glomerular model for evaluating blood filtration, an endometrial model for developing a new treatment and a DDS of hepatocyte growth factor for improving liver disorder.
  • Immunosuppressive Effects of Regulatory Dendritic Cells Induced by NK026680.
    Susumu Shibasaki; Kenichiro Yamashita; Ryoichi Goto; Kenji Wakayama; Gentaro Hirokata; Yusuke Tsunetoshi; Masaaki Zaitsu; Rumi Igarashi; Sanae Haga; Yoshiki Yanagawa; Michitaka Ozaki; Satoru Todo
    AMERICAN JOURNAL OF TRANSPLANTATION, 10, 560, 561, Apr. 2010, [Peer-reviewed]
    English
  • HEPATIC ISCHEMIA INDUCED IMMEDIATE OXIDATIVE STRESS AFTER REPERFUSION AND DETERMINED THE SEVERITY OF THE REPERFUSION-INDUCED DAMAGE. - IN VIVO DYNAMIC ANALYSIS OF LIVER OXIDATIVE STRESS AND DAMAGE
    Ozaki Michitaka; Haga Sanae; Remington S. James; Morita Naoki; Ozawa Takeaki
    HEPATOLOGY, 50, 4, 640A, Oct. 2009, [Peer-reviewed]
  • Hepatic Ischemia Induced Immediate Oxidative Stress after Reperfusion and Determined the Severity of the Reperfusion-Induced Damage
    Sanae Haga; S. James Remington; Naoki Morita; Keita Terui; Michitaka Ozaki
    ANTIOXIDANTS & REDOX SIGNALING, 11, 10, 2563, 2572, Oct. 2009, [Peer-reviewed]
    English, Scientific journal
  • マウスモデルにおける新規NF-kB阻害剤DHMEQの膵癌腹膜播種抑制効果(A novel NF-κB inhibitor DHMEQ suppressed pancreas cancer progression in a mouse model of peritoneal dissemination)
    佐藤 正法; 尾崎 倫孝; 中西 一彰; 渡邉 俊之; 三野 和宏; 芳賀 早苗; 横尾 英樹; 梅澤 一夫; 近江谷 克祐; 神山 俊哉; 藤堂 省
    日本癌学会総会記事, 68回, 481, 481, 日本癌学会, Aug. 2009
    English
  • The Survival Pathways Phosphatidylinositol-3 Kinase (PI3-K)/Phosphoinositide-Dependent Protein Kinase 1 (PDK1)/Akt Modulate Liver Regeneration Through Hepatocyte Size Rather Than Proliferation
    Sanae Haga; Michitaka Ozaki; Hiroshi Inone; Yasuo Okamoto; Wataru Ogawa; Kiyoshi Takeda; Shizuo Akira; Satoru Todo
    HEPATOLOGY, 49, 1, 204, 214, Jan. 2009, [Peer-reviewed]
    English, Scientific journal
  • Mutual modulation between interleukin-10 and interleukin-6 induced by Rhodococcus aurantiacus infection in mice
    Yimin; Masashi Kohanawa; Michitaka Ozaki; Sanae Haga; Keiko Fujikawa; Songji Zhao; Yuji Kuge; Nagara Tamaki
    MICROBES AND INFECTION, 10, 14-15, 1450, 1458, Nov. 2008, [Peer-reviewed]
    English, Scientific journal
  • マウス胃癌腹膜播種モデルにおける、新規NF-κB阻害剤DHMEQの腫瘍抑制効果の検討(A novel NF-κB inhibitor DHMEQ suppresses the expansion of gastric cancer in the mouse peritoneal dissemination model)
    三野 和宏; 中西 一彰; 喜納 政哉; 佐藤 正法; 芳賀 早苗; 横尾 英樹; 神山 俊哉; 梅澤 一夫; 尾崎 倫孝; 藤堂 省
    日本癌学会総会記事, 67回, 183, 183, 日本癌学会, Sep. 2008
    English
  • Identification of de novo STAT3 target gene in liver regeneration
    Hui-Qi Zhang; Sanae Haga; Moto Fukai; Yuko Oikawa; Hiroshi Inoue; Wataru Ogawa; Arihiko Kano; Atsushi Maruyama; Xin-Yuan Fu; Satoru Todo; Shin Enosawa; Michitaka Ozaki
    Hepatology Research, 38, 4, 374, 384, Apr. 2008, [Peer-reviewed]
    English, Scientific journal
  • Preventing hypoxia/reoxygenation damage to hepatocytes by p66(shc) ablation: Up-regulation of anti-oxidant and anti-apoptotic proteins
    Sanae Haga; Keita Terui; Moto Fukai; Yuko Oikawa; Kaikobad Irani; Hiroyuki Furukawa; Satoru Todo; Michitaka Ozaki
    JOURNAL OF HEPATOLOGY, 48, 3, 422, 432, Mar. 2008, [Peer-reviewed]
    English, Scientific journal
  • Mechanism of impaired regeneration of fatty liver in mouse partial hepatectomy model
    Hiroshi Murata; Takahito Yagi; Hiromi Iwagaki; Tetsuya Ogino; Hiroshi Sadamori; Hiroyoshi Matsukawa; Yuzoh Umeda; Sanae Haga; Noriaki Takaka; Michitaka Ozaki
    JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, 22, 12, 2173, 2180, Dec. 2007, [Peer-reviewed]
    English, Scientific journal
  • Control of allograft rejection by applying a novel nuclear factor-kappa B inhibitor, dehydroxymethylepoxyquinomicin
    Shinya Ueki; Kenichiro Yamashita; Takeshi Aoyagi; Sanae Haga; Tomomi Suzuki; Tomoo Itoh; Masahiko Taniguchi; Tsuyoshi Shimamura; Hiroyuki Furukawa; Michitaka Ozaki; Kazuo Umezawa; Satoru Todo
    TRANSPLANTATION, 82, 12, 1720, 1727, Dec. 2006, [Peer-reviewed]
    English, Scientific journal
  • Protective effects of nafamostat mesilate on liver injury induced by lipopolysaccharide in rats: Possible involvement of CD14 and TLR-4 downregulation on Kupffer cells
    Hideaki Miyaso; Yoshinori Morimoto; Michitaka Ozaki; Sanae Haga; Susumu Shinoura; Yasuhiro Choda; Hiroshi Murata; Goutaro Katsuno; Kamul Huda; Hideo Takahashi; Noriaki Tanaka; Hiromi Iwagaki
    DIGESTIVE DISEASES AND SCIENCES, 51, 11, 2007, 2012, Nov. 2006, [Peer-reviewed]
    English, Scientific journal
  • Ex vivo adenoviral gene transfer of constitutively activated STAT3 reduces post-transplant liver injury and promotes regeneration in a 20% rat partial liver transplant model
    KASM Huda; L Guo; S Haga; H Murata; T Ogino; M Fukai; T Yagi; H Iwagaki; N Tanaka; M Ozaki
    TRANSPLANT INTERNATIONAL, 19, 5, 415, 423, May 2006, [Peer-reviewed]
    English, Scientific journal
  • Obstructive jaundice increases sensitivity to lipopolysaccharide via TLR4 upregulation: Possible involvement in gut-derived hepatocyte growth factor-protection of hepatocytes
    H Miyaso; Y Morimoto; M Ozaki; S Haga; S Shinoura; Y Choda; H Iwagaki; N Tanaka
    JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, 20, 12, 1859, 1866, Dec. 2005, [Peer-reviewed]
    English, Scientific journal
  • Compensatory recovery of liver mass by Akt-mediated hepatocellular hypertrophy in liver-specific STAT3-deficient mice
    S Haga; W Ogawa; H Inoue; K Terui; T Ogino; R Igarashi; K Takeda; S Akira; S Enosawa; H Furukawa; S Todo; M Ozaki
    JOURNAL OF HEPATOLOGY, 43, 5, 799, 807, Nov. 2005, [Peer-reviewed]
    English, Scientific journal
  • Stat3 confers resistance against hypoxia/reoxygenation-induced oxidative injury in hepatocytes through upregulation of Mn-SOD
    K Terui; S Enosawa; S Haga; HQ Zhang; H Kuroda; K Kouchi; T Matsunaga; H Yoshida; JF Engelhardt; K Irani; N Ohnuma; M Ozaki
    JOURNAL OF HEPATOLOGY, 41, 6, 957, 965, Dec. 2004, [Peer-reviewed]
    English, Scientific journal
  • Improved hepatic regeneration with reduced injury by redox factor-1 in a rat small-sized liver transplant model
    L Guo; S Haga; S Enosawa; K Naruse; Y Harihara; Y Sugawara; K Irani; M Makuuchi; M Ozaki
    AMERICAN JOURNAL OF TRANSPLANTATION, 4, 6, 879, 887, Jun. 2004, [Peer-reviewed]
    English, Scientific journal
  • Hypoxia/re-oxygenation-induced, redox-dependent activation of STAT1 (signal transducer and activator of transcription 1) confers resistance to apoptotic cell death via hsp70 induction
    K Terui; S Haga; S Enosawa; N Ohnuma; M Ozaki
    BIOCHEMICAL JOURNAL, 380, Pt 1, 203, 209, May 2004, [Peer-reviewed]
    English, Scientific journal
  • Role of STAT-3 in regulation of hepatic gluconeogenic genes and carbohydrate metabolism in vivo
    H Inoue; W Ogawa; M Ozaki; S Haga; M Matsumoto; K Furukawa; N Hashimoto; Y Kido; T Mori; H Sakaue; K Teshigawara; SY Jin; H Iguchi; R Hiramatsu; D LeRoith; K Takeda; S Akira; M Kasuga
    NATURE MEDICINE, 10, 2, 168, 174, Feb. 2004, [Peer-reviewed]
    English, Scientific journal
  • Stat3 protects against Fas-induced liver injury by redox-dependent and -independent mechanisms
    S Haga; K Terui; HQ Zhang; S Enosawa; W Ogawa; H Inoue; T Okuyama; K Takeda; S Akira; T Ogino; K Irani; M Ozaki
    JOURNAL OF CLINICAL INVESTIGATION, 112, 7, 989, 998, Oct. 2003, [Peer-reviewed]
    English, Scientific journal
  • Inhibition of hypoxia/reoxygenation-induced oxidative stress in HGF-stimulated antiapoptotic siqnaling: role of P13-K and Akt kinase upon rac1
    M Ozaki; S Haga; HQ Zhang; K Irani; S Suzuki
    CELL DEATH AND DIFFERENTIATION, 10, 5, 508, 515, May 2003, [Peer-reviewed]
    English, Scientific journal
  • Overexpression of redox factor-1 protects against postischemic liver injury by reducing oxidative stress and NF-kappa B activity .
    M.Ozaki; S.Haga; K. Irani; H.Amemiya; S.Suzuki
    Transplantation Proceedings, 34, 2640, 2642, 2002, [Peer-reviewed]
■ Other Activities and Achievements
■ Lectures, oral presentations, etc.
  • 光プローブをもちいた肝の酸化ストレスと傷害（プログラム細胞死）の観察と評価
    尾崎 倫孝; 芳賀 早苗; 森田 直樹; 小澤 岳昌
    第28回肝細胞研究会, 10 Sep. 2021, Public symposium
    10 Sep. 2021 - 11 Sep. 2021
  • 肝虚血再灌流傷害進展における Poly（ADP-ribose）polymerase（PARP）依存性細胞死の解析
    尾崎 倫孝; 芳賀 早苗; 浅野 真未; 菅野 憲; 小澤 岳昌; 森田 直樹
    第27回肝細胞研究会, 15 Dec. 2020, Oral presentation
    16 Dec. 2020
  • 様々な様式の細胞死は、慢性脂肪肝における遷延化した組織傷害に関与する可能性がある
    芳賀 早苗; 森田 直樹; 小澤 岳昌; 尾崎 倫孝
    第93回日本生化学会大会, Poster presentation
    14 Sep. 2020 - 16 Sep. 2020
  • Analysis of programmed cell death in hepatocytes induced by Fas ligand and oxidative stress
    Haga S; Morita N; Ozaki M
    第92回日本生化学会総会, 20 Sep. 2019, Japanese, Poster presentation
    [Domestic Conference]
  • 脂肪肝における易傷害性メカニズム解析の基礎的研究
    芳賀早苗; 浅野真未; 森田直樹; 尾崎倫孝
    第26回肝細胞研究会, 24 May 2019, Japanese, Poster presentation
    [Domestic Conference]
  • Relevance of FXR-p62/SQSTM1 pathway for survival and protection of mouse hepatocytes and liver with steatosis.
    Michitaka Ozaki; Sanae Haga; Yimi
    IBD and Liver: East Meets West, 2018
    Kyoto Hotel Okura, Kyoto
  • 「発光プローブによるプログラム細胞死（アポトーシス、ネクロプトーシス）動的解析の試み」
    芳賀 早苗; 菅野 憲; 小澤 岳昌; 森田 直樹; 浅野 真未; 伊 敏; 尾崎 倫孝
    第27回日本Cell Death学会, 2018
    京都府立医科大学 図書館ホール、京都
  • 「光による細胞生存能（Akt/PKB分子）制御に関する研究」
    芳賀 早苗; 小澤 岳昌; 森田 直樹; 伊 敏; 尾崎 倫孝
    第91回日本生化学会, 2018
    国立京都国際会館、京都
  • 「マウス脂肪肝モデルをもちいたビルベリーの予防効果に関する検討」
    芳賀 早苗; 伊 敏; 森田 直樹; 浅野 真未; 荘厳 哲哉; 尾崎 倫孝
    第39会日本肥満学会, 2018
    神戸国際会議場、神戸
  • 「レドックスが制御するネクローシス型細胞死（ネクロプトーシス）の光プローブによる動的解析」
    芳賀 早苗; 菅野 憲; 小澤 岳昌; 森田 直樹; 浅野 真未; 尾崎 倫孝
    第25回肝細胞研究会, 2018
    東京大学伊藤謝恩ホール、東京
  • 「光プローブをもちいたプログラム細胞死（アポトーシス、ネクロプトーシス）の動的解析」
    尾崎 倫孝; 芳賀 早苗
    第22回日本がん分子標的治療学会学術集会, 2018
    都市センターホテル、東京
  • Spatio-temporal imaging of cell/organ physio-pathology and its clinical application.
    Michitaka Ozaki; Sanae Haga; Toshiyuki Hamada; Takeaki Ozawa; Yuma Yamada
    CIS Workshop 2017 “Innovative Bio-imaging toward Diagnosis and Therapy”, 2017
    Hokkaido University, Sapporo
  • 脂肪化肝細胞・脂肪肝に対するビルベリーの効果とその機序の検討
    芳賀 早苗; 荘厳 哲哉; 伊 敏; 森田 直樹; 浅野 真未; 尾崎 倫孝
    第24回肝細胞研究会, 2017
    旭川市民文化会館、旭川
  • 肝核内受容体FXRはp62/SQSTM1およびSHPを経由して、それぞれ抗酸化・細胞保護効果、脂肪化抑制効果を示す
    尾崎 倫孝; 芳賀 早苗; 伊 敏
    第24回肝細胞研究会, 2017
    旭川市民文化会館、旭川
  • マウス脂肪化肝細胞・脂肪肝に対するビルベリーの抑制効果の検討
    芳賀 早苗; 荘厳 哲哉; 伊 敏; 森田 直樹; 浅野 真未; 尾崎 倫孝
    第38回日本肥満学会, 2017
    大阪国際会議場、大阪
  • 肝細胞におけるレドックス依存性ネクロプトーシスの動態解析
    芳賀 早苗; 菅野 憲; 小澤 岳昌; 森田 直樹; 浅野 真未; 伊 敏; 尾崎 倫孝
    ConBio2017, 2017
    神戸国際会議場、神戸
  • ビルベリー抽出物の糖尿病性網膜症発症・進行予防効果に関する基礎的研究
    浅野 真未; 芳賀 早苗; 柴崎 彩; 黒澤 和也; 荘厳 哲哉; 尾崎 倫孝
    ConBio2017, 2017
    神戸国際会議場、神戸
  • カスパーゼ3プローブ発現細胞を用いたクラミジア感染宿主細胞内のアポトーシス制御機構の探索
    松尾 淳司; 芳賀 早苗; 大久保 寅彦; 中村 眞二; 小澤 岳昌; 尾崎 倫孝; 山口 博之
    ConBio2017, 2017
    神戸国際会議場、神戸
  • Optical evaluation and monitoring of oxidative stress & damage in vivo.
    Sanae Haga; Takeaki Ozawa; Naoki Morita; Mami Asano; James Remington; Michitaka Ozaki
    19th International Symposium on Bioluminescence & Chemiluminescence(ISBC2016)., 2016
    Epochal Tsukuba
  • Long-term ex vivo and in vivo monitoring of tumor progression by using dual luciferases.
    Naoki Morita; Sanae Haga; Yoshihiro Ohmiya; Michitaka Ozaki
    19th International Symposium on Bioluminescence & Chemiluminescence (ISBC2016)., 2016
    Epochal Tsukuba
  • Function of Toll-like receptor 2 in the murine inflammatory response to Rhodococcus aurantiacus infection.
    Yimin; Masashi Kohanawa; Sanae Haga; Michitaka Ozaki
    4th Annual Meeting of the International Cytokine and Interferon Society (ICIS) ．, 2016
    San Francisco
  • ビルベリーによる非アルコール性脂肪肝炎(NASH)の予防に向けた基礎的検討」（ポスター）
    芳賀 早苗; 荘厳 哲哉; 森田 直樹; 浅野 真未; 尾崎 倫孝
    第23回肝細胞研究会, 2016
    大阪大学中之島センター、大阪
  • ビルベリーの糖尿病性網膜症初期病変抑制効果の検討
    芳賀早苗; 荘厳哲哉; 森田直樹; 浅野真未; 尾崎倫孝
    第89回日本生化学会大会, 2016
    仙台国際センター、仙台
  • 光プローブをもちいた時空間的病態解析と積極的病態制御の試み
    尾崎 倫孝; 芳賀 早苗; 小澤 岳昌; 山田 勇磨
    第71回日本消化器外科学会総会 特別企画「光エネルギーの医療への展開」（, 2016
    あわぎんホール、徳島
  • FXRを起点とした脂肪肝傷害抑制と 脂肪化改善の機序
    尾崎 倫孝; 芳賀 早苗; 森田 直樹
    第25回日本肝臓医生物学研究会；LBSG-J（プロメテウスの会）, 2016
    ナスパニューオータニ、新潟
  • 「光技術を用いた臓器・細胞機能評価と制御の可能性」
    尾崎倫孝; 芳賀早苗; 小澤岳昌; 森田直樹; 浜田俊幸
    第43回日本臓器保存生物医学会学術集会, 2016
    東京薬科大学、東京
  • “光”を利用した肝細胞機能制御技術の開発
    芳賀 早苗; 小澤 岳昌; 森田 直樹; 野田 なつみ; 尾崎 倫孝
    第22回肝細胞研究会 ポスターセッション6「創薬・新しい実験系の開発」, 2015
    米子コンベンションセンター、鳥取
  • 統合的ストレス応答による脂肪肝再生障害の分子メカニズムの解明
    稲葉 有香; 芳賀 早苗; 尾崎 倫孝; 春日 雅人; 井上 啓
    第22回肝細胞研究会 一般口演5「肝再生」, 2015
    米子コンベンションセンター、鳥取
  • 脂肪肝における肝切除後肝傷害・肝再生不全の機序について
    尾崎 倫孝; 芳賀 早苗; 小澤 岳昌; 森田 直樹; 井上 啓; 稲葉 有香
    第22回肝細胞研究会, 2015
    米子コンベンションセンター、鳥取県
  • 光技術を応用した移植臓器（組織）のモニタリングと制御の試み
    尾崎 倫孝; 芳賀 早苗; 森田 直樹; 伊 敏; 菅野 憲; 小澤 岳昌
    第51回日本移植学会総会, 2015
    ホテル日航熊本、熊本県
  • Development of a novel in vivo optic imaging technology for biological diagnosis and therapy. (生物学的診断と治療のための新たな生体光イメージング技術の開発)
    Michitaka Ozaki; Sanae Haga; Naoki Morita; Min Yi; Yuma Yamada; Takeaki Ozawa
    第74回 日本癌学会学術総会, 2015
    名古屋国際会議場、名古屋
  • p62/SQSTM1 を基軸とした新たな肝臓・肝細胞保護・機能維持法の探索
    尾崎 倫孝; 芳賀 早苗; 森田 直樹; 伊 敏
    第42回日本臓器保存生物医学会学術集会、シンポジウム, 2015
    いわて県民情報交流センター、岩手
  • p62/SQSTM1が制御する肝細胞障害機序の解析
    芳賀 早苗; 小澤 岳昌; 山田 勇磨; 森田 直樹; 野田 なつみ; 尾崎 倫孝
    第21回肝細胞研究会, 2014
    東京医科歯科大学、東京
  • 高血糖および脂肪化状態が肝虚血/再灌流傷害に及ぼす影響 Impact of high glucose and steatosis upon ischemia/reperfusion-induced liver injury in mouse.
    芳賀 早苗; 小澤 岳昌; 森田 直樹; 野田 なつみ; 尾崎 倫孝
    第87回日本生化学会, 2014
    京都国際会議場、京都
  • 光イメージング技術を用いた肝病態の解析
    尾崎 倫孝; 芳賀 早苗; 野田 なつみ; 森田 直樹; 小澤 岳昌
    第21回肝細胞研究会 シンポジウム1「肝疾患の病態を制御するメカニズム」, 2014
    東京医科歯科大学、東京
  • “ 光” を利用した新たな細胞・臓器保存法の開発
    芳賀 早苗; 小澤 岳昌; 森田 直樹; 野田 なつみ; 尾崎 倫孝
    第41回日本臓器保存生物医学会学術集会 平成25 年度日本臓器保存生物医学会奨励賞 受賞記念講演, 2014
    千里ライフサイエンスセンター、大阪
■ Research Themes
  • Development of a breakthrough molecular targeted therapy against deep cancer using near-infrared light with longer wavelength (NIR-II).
    Grants-in-Aid for Scientific Research
    30 Jun. 2022 - 31 Mar. 2025
    森田 直樹; 佐原 健彦; 芳賀 早苗; 尾崎 倫孝
    短波赤外光領域の波長900（1000）-1400nmの光（NIR-II）は、生体内深部まで到達可能で細胞傷害性も低いことが知られているが、NIR-IIを直接利用した生体内 分子の光操作の研究は進んでいない。本研究では、NIR-IIに直接応答する新たな遺伝子の探索を行い、光操作にて生体内深部がん治療に応用可能かどうかを研究 する。具体的には、出芽酵母（Saccharomyces cerevisiae）及び微細緑藻クラミドモナス（Chlamydomonas reinhardii）を用いて、NIR-IIに応答する遺伝子プロモーターの探索、同プロモーターを利用した細胞死誘導タンパク質の誘導発現とその腫瘍細胞への効果を細胞レベル及び動物レベルで検証することを目的とする。
    まず、RNA-seq解析に必要な出芽酵母およびクラミドモナスのゲノム情報、転写産物情報、各種アノテーション情報をデータベースより取得し、RNA-seq解析に必要なデータ解析環境を整備した。経時的（1h、4h、8h、24h）に細胞をサンプリングし、RNA-seq解析を行う予定であったが、先ずは、NIR-II照射によって、遺伝子発現に差が出るか否かを確認するために、NIR-II照射前（0 h）と照射後（6 h）の細胞からRNA抽出を行い、RNA-seq解析を行うこととした。出芽酵母は30℃でOD600が1.0になるまで、クラミドモナスは25℃でOD680が1.0まで培養した後、近赤外照射用のインキュベーターにフラスコごと移し、NIR-IIを照射し各々培養した。NIR-II照射前（0 h）と照射後（6 h）の細胞からRNA抽出を行い、RNA-seq解析を行ったがうまくデータが得られなかった。現在、改めてNIR-II照射実験から行い、RNAの調製を行っている。
    Japan Society for the Promotion of Science, Grant-in-Aid for Challenging Research (Exploratory), National Institute of Advanced Industrial Science and Technology, 22K19576
  • 異なる特性をもつ二種類の光を利用した生体内深部組織の修復・再生法の開発
    科学研究費助成事業
    01 Apr. 2021 - 31 Mar. 2024
    尾崎 倫孝; 小澤 岳昌; 森田 直樹; 芳賀 早苗
    日本学術振興会, 基盤研究(B), 北海道大学, 21H02983
  • 薬理的神経制御を用いた新たな脳卒中運動療法の開発に対する生体脳イメージングの応用
    科学研究費助成事業
    01 Apr. 2020 - 31 Mar. 2024
    前島 洋; 真先 敏弘; 榊間 春利; 高松 泰行; 芳賀 早苗; 尾崎 倫孝
    昨年度までに得られた所見として、トレッドミル運動、或いはα5サブユニットを含むGABA受容体の特異的阻害薬L-655,708投与の単独介入による脳出血後の運動機能回復は限定的であるが、両者を組み合わせた介入により相乗的な回復効果が確認されていた。本年度は、これらの個体から採取した脳・脊髄サンプルの解析を進め、併用介入群に生じた可塑性修飾について検証を行った。L-655,708投与により大脳皮質運動野BDNF発現の増強が認められた。加えて、併用介入群の脊髄においては、 シナプスや軸索の可塑性に関与する分子マーカーの発現増強が認められた。このことから、併用介入群の効果的な機能回復には、脳内だけでなく脊髄における可塑性修飾も重要であることが示唆された。
    脳におけるBDNF発現の生体イメージング計測を目的に、BDNFのプロモーター域に蛍発光酵素Luciferase遺伝子を挿入したBDNF-Luc Tgマウスを繁殖、飼育した。このTgマウスを対象に脳深部の発光の検知を可能とする発光基質AkaLumine-HCl (TokeOni)を腹腔内投与後、脳領域の発光を運動介入後に経時的に定量する一連の手法を開発した。この生体脳イメージングの手法を用いて、トレッドミル運動がBDNF発現に与える効果について検証を行った。単回のトレッドミル運動後４-8時間内において脳領域における発光、即ちBDNF発現が増強され、更に２週間のトレッドミル運動の継続することで運動後のより早いタイミングにBDNF発現増強が生じることを確認した。
    一方、この生体脳イメージングを脳出血モデルに対して応用する際に、これまでのステレオタキシックシステムを用いた微量コラゲナーゼ注入によるモデル作成において、計測脳領域の皮膚処理が発光に影響を与える問題が生じ、術時における頭部の皮膚切開、縫合部位について検討を要することが示唆された。
    日本学術振興会, 基盤研究(B), 北海道大学, 20H04048
  • 細胞内Ca2+と活性酸素が誘導するプログラム細胞死による肝虚血再灌流傷害の新展開
    Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)
    Apr. 2020 - Mar. 2024
    芳賀 早苗; 森田 直樹; 尾崎 倫孝
    本研究は、虚血および再灌流時に肝細胞内で引き起こされる『活性酸素』, 『細胞内カルシウムイオン』, そして『（ネクローシス様）プログラム細胞死』に着目し、これまでの概念では説明しきれない肝傷害誘導機序の存在を明らかにすることを目的とする。この研究は、特に肝傷害の維持・拡大におおきく関わる、再灌流後中～後期の持続的な肝傷害をターゲットとし、新たな肝虚血再灌流傷害機構の解明に挑み、新たな標的分子・機序を導き出す意義を持つ。
    本研究では、「ネクロプトーシス」、「パータナトス」など種々のネクローシス様プログラム細胞死等と、低酸素/再酸素化時に肝細胞内で引き起こされる様々なイベント、環境変化(①酸化ストレス、②細胞内カルシウムイオン(Ca2+)濃度―CaMKⅡ）の機序を段階的に進める計画である。
    本年度は昨年度の研究成果を取りまとめるとともに、引き続き上記計画に則り研究を進めた。昨年度から着手している低酸素/再酸素化時の細胞内カルシウムイオン―CaMKⅡを介したネクロプトーシスの分子機序の解析を進め、この細胞死の機序や意義を解析した。これに関連して、ネクロプトーシスと他のプログラム細胞死との相互関係や相違についての解析も進めた。また、昨年度から取り掛かっている肝虚血/再灌流モデルにおける肝細胞死解析に関しては、ターゲットを抑制した条件での検討段階まで解析を進めた。また、各プログラム細胞死の重要性・機能性を検討するためのツールの開発に関して、事調査及び構想を固めることができた。
    以上のように、本年度も肝細胞および生体肝で引き起こされる細胞死の機能性とその誘導機序について、基盤から応用までの検討を進めることができた。
    Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (C), Hokkaido University, Principal investigator, 20K08299
  • ランタニド・ナノ粒子（LNP）を利用した癌細胞特異的光治療法の開発
    挑戦的研究（開拓）
    Apr. 2019 - Mar. 2023
    尾崎 倫孝
    文部科学省, Competitive research funding
  • 肝虚血・再灌流傷害における多段階多元的傷害進展のメカニズム解析
    基盤研究(B)
    Apr. 2019 - Mar. 2023
    森田 直樹
    文部科学省, Competitive research funding
  • 生体細胞内分子の時空間的ダイナミズム解析のためのイメージング技術開発
    「医学系研究奨励（がん領域・基礎）」
    2016 - 2019
    芳賀早苗
    公益財団法人 武田科学振興財団, Principal investigator, Competitive research funding
  • 分子標的治療薬の非侵襲的・時空間的モニタリングに向けた革新的イメージング技術開発
    科学研究費 若手研究（Ａ）
    2015 - 2019
    芳賀早苗
    文部科学省, Principal investigator, Competitive research funding
  • 分子イメージングを基軸とする生細胞内分子計測・光操作法の開発
    科学研究費 基盤研究（Ｓ）
    2014 - 2019
    小澤岳昌
    文部科学省, Competitive research funding
  • 新規マーカーによるNASH予防・診断・治療のための食品・薬剤探索システムの構築
    科学研究費 基盤研究（Ｂ）
    2015 - 2018
    森田直樹
    文部科学省, Competitive research funding
  • 膵癌の機能的診断を目標とした新規バイオマーカーの開発
    科学研究費 挑戦的萌芽研究
    2015 - 2018
    増井俊彦
    文部科学省, Competitive research funding
  • 膵癌における新たな細胞内分子ターゲットによる生物学的診断・治療法の開発
    科学研究費 挑戦的萌芽研究
    2015 - 2018
    森田直樹
    文部科学省, Competitive research funding
  • 光による細胞機能制御による新規細胞療法の開発
    科学研究費 挑戦的萌芽研究
    2014 - 2017
    芳賀早苗
    文部科学省, Principal investigator, Competitive research funding
  • 原始クラミジアが共生するアメーバは何故レジオネラの感染から回避できるのか
    科学研究費 挑戦的萌芽研究
    2014 - 2016
    山口博之
    文部科学省, Competitive research funding
  • 細胞死による積極的な肝機能維持・再生制御機構の解明と臨床応用に向けた研究
    科学研究費 挑戦的萌芽研究
    2014 - 2016
    伊 敏
    文部科学省, Competitive research funding
  • 多重ストレス時における精神活動変化の可視化とストレスマネジメント方略
    科学研究費 挑戦的萌芽研究
    2013 - 2016
    溝部佳代
    文部科学省, Competitive research funding
  • 定量的生体分子イメージング・操作法の開発
    科学研究費 基盤研究（Ａ）
    2014 - 2015
    小澤岳昌
    文部科学省, Competitive research funding
  • NAFLDに伴う肝再生障害に対する抗GADD34作用の有用性の検討
    科学研究費 若手研究（Ｂ）
    2013 - 2015
    稲葉有香
    文部科学省, Competitive research funding
  • 肝ストレスの動的解析による肝機能障害・予備能の評価
    科学研究費 挑戦的萌芽研究
    2012 - 2014
    佐藤直樹
    文部科学省, Competitive research funding
  • 生きた細胞内でのオートファジー発光定量法の開発
    科学研究費 若手研究（Ｂ）
    2012 - 2014
    服部満
    文部科学省, Competitive research funding
  • 光プローブを応用した生体イメージング法による画期的術中ライブ診断法の開発
    科学研究費 基盤研究（Ａ）
    2011 - 2014
    尾崎倫孝
    文部科学省, Competitive research funding
  • ヒスチジン誘導体の糖代謝における役割
    科学研究費 基盤研究（Ｂ）
    2011 - 2014
    井上啓
    文部科学省, Competitive research funding
  • 腹腔内転移のバイオイメージングと抑制物質の分子デザイン
    科学研究費 基盤研究（Ｂ）
    2011 - 2014
    梅澤一夫
    文部科学省, Competitive research funding
  • 細胞情報伝達に関わる蛋白質活性を可視化する発光プローブ分子の開発
    科学研究費 基盤研究（Ｂ）
    2011 - 2014
    森田直樹
    文部科学省, Competitive research funding
  • 心停止下肝移植への臨床応用をめざした肝グラフト灌流保存法の開発
    科学研究費 挑戦的萌芽研究
    2011 - 2012
    古川博之
    文部科学省, Competitive research funding
  • 新規分泌型発光デュアルプローブを用いたｉｎ ｖｉｖｏ での癌細胞上皮間葉移行解析
    科学研究費 挑戦的萌芽研究
    2011 - 2012
    片岡昭彦
    文部科学省, Competitive research funding
  • 細胞死(オートファジー・アポトーシス)による肝再生制御メカニズムの解析
    科学研究費 挑戦的萌芽研究
    2011 - 2012
    尾崎倫孝
    文部科学省, Competitive research funding
  • 生体分子機能イメージングによる種々の肝病態におけるストレス応答の解析
    科学研究費 特別研究員奨励費
    2010 - 2012
    芳賀早苗
    文部科学省, Principal investigator, Competitive research funding
  • 臓器ストレス測定法の開発と外科領域への応用
    科学研究費 挑戦的萌芽研究
    2010 - 2011
    藤堂省
    文部科学省, Competitive research funding
  • 分泌型光プローブによる生体内リポーターシステムの開発と腫瘍診断・治療法への応用
    科学研究費 挑戦的萌芽研究
    2009 - 2010
    尾崎倫孝
    文部科学省, Competitive research funding
  • 光プローブをもちいたバイオイメージングによる多角的診断・治療法の開発
    科学研究費 基盤研究（Ａ）
    2008 - 2010
    尾崎倫孝
    文部科学省, Competitive research funding
  • 分子機能プローブ導入による生体内臓器機能イメージングに関する研究
    科学研究費 特別研究員奨励費
    2008 - 2009
    芳賀早苗
    文部科学省, Principal investigator, Competitive research funding
  • 生体材料(コラーゲンビトリゲル)をもちいた新しい治療材料の開発
    科学研究費 挑戦的萌芽研究
    2008 - 2009
    古川博之
    文部科学省, Competitive research funding
  • CHIP-chip法/Oligofish法によるヒトがん組織の網羅的転写機能解析
    科学研究費 基盤研究（Ｃ）
    2007 - 2008
    中西一彰
    文部科学省, Competitive research funding
  • 新規分子機能プローブ開発による生体・臓器内分子機能診断への応用
    科学研究費 萌芽研究
    2007 - 2008
    尾崎倫孝
    文部科学省, Competitive research funding
  • 生活関連化学物質の皮膚感作性等のインビトロ評価法に関する研究
    科学研究費 基盤研究（Ｃ）
    2006 - 2008
    内野正国
    文部科学省, Competitive research funding
  • 消化器外科領域における分子標的治療に向けた包括的基盤研究
    科学研究費 基盤研究（Ｂ）
    2005 - 2007
    尾崎倫孝
    文部科学省, Competitive research funding
  • 肝移植代替治療をめざした胎児肝内への同種・異種細胞移植の生着・増殖条件の検討
    科学研究費 基盤研究（Ｃ）
    2001 - 2002
    絵野沢伸
    文部科学省, Competitive research funding