研究者基本情報

• 獣医学博士, 北海道大学, 2012年06月

• https://researchmap.jp/ohnom

• https://jglobal.jst.go.jp/detail?JGLOBAL_ID=202001001725586313
• https://orcid.org/0000-0003-1086-8244

• 50794202

• https://orcid.org/0000-0003-1086-8244

• 202001001725586313

• 博士課程, 国際感染症学院

研究活動情報

• 2013年03月, 北海道大学, 大塚賞
• 2011年09月, 日本カロテノイド研究会, 第一回奨励賞
  44825116
• 2009年03月, 日本獣医師会, 日本獣医師会長賞

• A Case of Infection with Leptospires from Three Different Serovars During a Flood in the Philippines.
  Yasutake Yanagihara; Toshiyuki Masuzawa; Masashi Shingai; Marumi Ohno; Toshiki Sekiya; Naoki Nomura; Tomomi Kawakita; Chimuka Handabile; Yuichi Koshiishi; Richard Obeng-Kyeremeh; Toshihiro Ito; Mitsumasa Saito; Sharon Y A M Villanueva; Nina G Gloriani; Hiroshi Kida
  The American journal of tropical medicine and hygiene, 113, 3, 674, 677, 2025年09月03日, ［国際誌］
  英語, 研究論文（学術雑誌）, Leptospirosis a significant and life-threatening zoonosis with global reach. If diagnosis and treatment are delayed, the infection may lead to fatal Weil's disease. In the Philippines, a 21-year-old man was admitted to the hospital with leptospirosis-like symptoms, including fever, myalgia, headache, anuria, jaundice, hemorrhage, skin rash, and diarrhea. Although he was immediately treated with penicillin G, the patient died shortly after admission. The serological test result was negative for Leptospira; however, three leptospires were isolated from the patient through selective cultivation under varying conditions. Microscopic agglutination tests and a phylogenetic analysis of the flaB gene encoding the flagellin subunit protein revealed that the isolates belonged to three different serovars, suggesting that the patient was simultaneously infected with at least three distinct Leptospira serovars. In this case report, we highlight the potential risk of multiple infections with leptospires in humans, a critical consideration for diagnosis and treatment strategies.
• ARNAX is an ideal adjuvant for COVID-19 vaccines to enhance antigen-specific CD4 + and CD8 + T-cell responses and neutralizing antibody induction
  Tomomi Kawakita; Toshiki Sekiya; Yayoi Kameda; Naoki Nomura; Marumi Ohno; Chimuka Handabile; Akari Yamaya; Hideo Fukuhara; Yuki Anraku; Shunsuke Kita; Shinsuke Toba; Hirotake Tsukamoto; Tomohiro Sawa; Hiroyuki Oshiumi; Yasushi Itoh; Katsumi Maenaka; Akihiko Sato; Hirofumi Sawa; Yasuhiko Suzuki; Lorena E. Brown; David C. Jackson; Hiroshi Kida; Misako Matsumoto; Tsukasa Seya; Masashi Shingai
  Journal of Virology, 2025年05月20日
  研究論文（学術雑誌）
• Optimization of the preparation method of inactivated intact virus particle vaccine for COVID-19.
  Marumi Ohno; Toshiki Sekiya; Richard Obeng-Kyeremeh; Chimuka Handabile; Minori Haruta; Naoki Nomura; Tomomi Kawakita; Masashi Shingai; Hiroshi Kida
  Vaccine, 56, 127173, 127173, 2025年04月24日, ［査読有り］, ［筆頭著者］, ［国際誌］
  英語, 研究論文（学術雑誌）, It has been recognized that it is difficult to maintain the virus particle structure of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which may be associated with lower immunogenicity of inactivated vaccines against coronavirus disease 2019 (COVID-19). We have previously demonstrated that an intact structure of the virus particles is critical for influenza inactivated whole virus particle vaccine (WPV) to be immunogenically potent. Here, we tested 37, 35, 33, and 31 °C for the virus propagation temperatures and the timing of formaldehyde treatment of the virus before and after centrifugation-based purification to obtain virus particles with an intact structure. Virus particles cultured at 33 °C retained spike proteins on the surface the most abundantly. The pretreatment of the virus with formaldehyde prevented the dissociation of the spike proteins from the viral surface during the centrifugation-based purification. The immunogenicity of the prepared vaccines, intact WPV and non-intact WPV that had lost the spike proteins, was evaluated in a mouse model. A single dose of intact WPV effectively induced humoral immunity compared to non-intact WPV, as indicated by higher titers of neutralizing antibodies. After a virus challenge, the mice vaccinated with a single dose of inactivated intact WPV showed less severe weight loss and lower virus titers in the lungs compared to those vaccinated with non-intact WPV. These results demonstrate the importance of the structural integrity of WPV in inducing effective and protective immunity, and provide significant insight into the development of COVID-19 WPV for practical use.
• Extraction of the CDRH3 sequence of the mouse antibody repertoire selected upon influenza virus infection by subtraction of the background antibody repertoire
  Masashi Shingai; Sayaka Iida; Naoko Kawai; Mamiko Kawahara; Toshiki Sekiya; Marumi Ohno; Naoki Nomura; Chimuka Handabile; Tomomi Kawakita; Ryosuke Omori; Junya Yamagishi; Kaori Sano; Akira Ainai; Tadaki Suzuki; Kazuo Ohnishi; Kimihito Ito; Hiroshi Kida
  Journal of Virology, 2024年03月19日
  研究論文（学術雑誌）
• Increased expression of CD38 on endothelial cells in SARS-CoV-2 infection in cynomolgus macaque
  Cong Thanh Nguyen; Misako Nakayama; Hirohito Ishigaki; Yoshinori Kitagawa; Akemi Kakino; Marumi Ohno; Masashi Shingai; Yasuhiko Suzuki; Tatsuya Sawamura; Hiroshi Kida; Yasushi Itoh
  Virology, 110052, 110052, Elsevier BV, 2024年03月
  研究論文（学術雑誌）
• Immunogenicity and protective efficacy of a co-formulated two-in-one inactivated whole virus particle COVID-19/influenza vaccine.
  Chimuka Handabile; Marumi Ohno; Toshiki Sekiya; Naoki Nomura; Tomomi Kawakita; Mamiko Kawahara; Masafumi Endo; Tomohiro Nishimura; Minako Okumura; Shinsuke Toba; Michihito Sasaki; Yasuko Orba; Brendon Y Chua; Louise C Rowntree; Thi H O Nguyen; Masashi Shingai; Akihiko Sato; Hirofumi Sawa; Kazumasa Ogasawara; Katherine Kedzierska; Hiroshi Kida
  Scientific reports, 14, 1, 4204, 4204, 2024年02月20日, ［国際誌］
  英語, 研究論文（学術雑誌）, Due to the synchronous circulation of seasonal influenza viruses and severe acute respiratory coronavirus 2 (SARS-CoV-2) which causes coronavirus disease 2019 (COVID-19), there is need for routine vaccination for both COVID-19 and influenza to reduce disease severity. Here, we prepared individual WPVs composed of formalin-inactivated SARS-CoV-2 WK 521 (Ancestral strain; Co WPV) or influenza virus [A/California/07/2009 (X-179A) (H1N1) pdm; Flu WPV] to produce a two-in-one Co/Flu WPV. Serum analysis from vaccinated mice revealed that a single dose of Co/Flu WPV induced antigen-specific neutralizing antibodies against both viruses, similar to those induced by either type of WPV alone. Following infection with either virus, mice vaccinated with Co/Flu WPV showed no weight loss, reduced pneumonia and viral titers in the lung, and lower gene expression of proinflammatory cytokines, as observed with individual WPV-vaccinated. Furthermore, a pentavalent vaccine (Co/qFlu WPV) comprising of Co WPV and quadrivalent influenza vaccine (qFlu WPV) was immunogenic and protected animals from severe COVID-19. These results suggest that a single dose of the two-in-one WPV provides efficient protection against SARS-CoV-2 and influenza virus infections with no evidence of vaccine interference in mice. We propose that concomitant vaccination with the two-in-one WPV can be useful for controlling both diseases.
• The elucidation of plasma lipidome profiles during severe influenza in a mouse model.
  Marumi Ohno; Siddabasave Gowda B Gowda; Toshiki Sekiya; Naoki Nomura; Masashi Shingai; Shu-Ping Hui; Hiroshi Kida
  Scientific reports, 13, 1, 14210, 14210, 2023年08月30日, ［査読有り］, ［筆頭著者］, ［国際誌］
  英語, 研究論文（学術雑誌）, Although influenza virus infection has been shown to affect lipid metabolism, details remain unknown. Therefore, we elucidated the kinetic lipid profiles of mice infected with different doses of influenza virus A/Puerto Rico/8/34 (H1N1) (PR8) by measuring multiple lipid molecular species using untargeted lipidomic analysis. C57BL/6 male mice were intranasally infected with PR8 virus at 50 or 500 plaque-forming units to cause sublethal or lethal influenza, respectively. Plasma and tissue samples were collected at 1, 3, and 6 days post-infection (dpi), and comprehensive lipidomic analysis was performed using high-performance liquid chromatography-linear trap quadrupole-Orbitrap mass spectrometry, as well as gene expression analyses. The most prominent feature of the lipid profile in lethally infected mice was the elevated plasma concentrations of phosphatidylethanolamines (PEs) containing polyunsaturated fatty acid (PUFA) at 3 dpi. Furthermore, the facilitation of PUFA-containing phospholipid production in the lungs, but not in the liver, was suggested by gene expression and lipidomic analysis of tissue samples. Given the increased plasma or serum levels of PUFA-containing PEs in patients with other viral infections, especially in severe cases, the elevation of these phospholipids in circulation could be a biomarker of infection and the severity of infectious diseases.
• Assessing the pyrogenicity of whole influenza virus particle vaccine in cynomolgus macaques.
  Marumi Ohno; Masataka Sagata; Toshiki Sekiya; Naoki Nomura; Masashi Shingai; Masafumi Endo; Kazuhiko Kimachi; Saori Suzuki; Cong Thanh Nguyen; Misako Nakayama; Hirohito Ishigaki; Kazumasa Ogasawara; Yasushi Itoh; Yoichiro Kino; Hiroshi Kida
  Vaccine, 41, 3, 787, 794, 2023年01月16日, ［査読有り］, ［筆頭著者］, ［国際誌］
  英語, 研究論文（学術雑誌）, Among inactivated influenza vaccines, the whole virus particle vaccine (WPV) elicits superior priming responses to split virus vaccine (SV) in efficiently inducing humoral and cellular immunity. However, there is concern for undesired adverse events such as fever for WPV due to its potent immunogenicity. Therefore, this study investigated the febrile response induced by subcutaneous injection with quadrivalent inactivated influenza vaccines of good manufacturing grade for pharmaceutical or investigational products in cynomolgus macaques. Body temperature was increased by 1 °C-2 °C for 6-12 h after WPV administration at the first vaccination but not at the second shot, whereas SV did not affect body temperature at both points. Given the potent priming ability of WPV, WPV-induced fever may be attributed to immune responses that uniquely occur during priming. Since WPV-induced fever was blunted by pretreatment with indomethacin (a cyclooxygenase inhibitor), the febrile response by WPV is considered to depend on the increase in prostaglandins synthesized by cyclooxygenase. In addition, WPV, but not SV, induced the elevation of type I interferons and monocyte chemotactic protein 1 in the plasma; these factors may be responsible for pyrogenicity caused by WPV, as they can increase prostaglandins in the brain. Notably, sufficient antibody responses were acquired by half the amount of WPV without causing fever, suggesting that excessive immune responses to trigger the febrile response is not required for acquired immunity induction. Thus, we propose that WPV with a reduced antigen dose should be evaluated for potential clinical usage, especially in naïve populations.
• Immunization with inactivated whole virus particle influenza virus vaccines improves the humoral response landscape in cynomolgus macaques.
  Brendon Y Chua; Toshiki Sekiya; Marios Koutsakos; Naoki Nomura; Louise C Rowntree; Thi H O Nguyen; Hayley A McQuilten; Marumi Ohno; Yuki Ohara; Tomohiro Nishimura; Masafumi Endo; Yasushi Itoh; Jennifer R Habel; Kevin J Selva; Adam K Wheatley; Bruce D Wines; P Mark Hogarth; Stephen J Kent; Amy W Chung; David C Jackson; Lorena E Brown; Masashi Shingai; Katherine Kedzierska; Hiroshi Kida
  PLoS pathogens, 18, 10, e1010891, 2022年10月, ［国際誌］
  英語, 研究論文（学術雑誌）, Although antibody-inducing split virus vaccines (SV) are currently the most effective way to combat seasonal influenza, their efficacy can be modest, especially in immunologically-naïve individuals. We investigated immune responses towards inactivated whole influenza virus particle vaccine (WPV) formulations, predicated to be more immunogenic, in a non-human primate model, as an important step towards clinical testing in humans. Comprehensive analyses were used to capture 46 immune parameters to profile how WPV-induced responses differed to those elicited by antigenically-similar SV formulations. Naïve cynomolgus macaques vaccinated with either monovalent or quadrivalent WPV consistently induced stronger antibody responses and hemagglutination inhibition (HI) antibody titres against vaccine-matched viruses compared to SV formulations, while acute reactogenic effects were similar. Responses in WPV-primed animals were further increased by boosting with the same formulation, conversely to modest responses after priming and boosting with SV. 28-parameter multiplex bead array defined key antibody features and showed that while both WPV and SV induced elevated IgG responses against A/H1N1 nucleoprotein, only WPV increased IgG responses against A/H1N1 hemagglutinin (HA) and HA-Stem, and higher IgA responses to A/H1N1-HA after each vaccine dose. Antibodies to A/H1N1-HA and HA-Stem that could engage FcγR2a and FcγR3a were also present at higher levels after one dose of WPV compared to SV and remained elevated after the second dose. Furthermore, WPV-enhanced antibody responses were associated with higher frequencies of HA-specific B-cells and IFN-γ-producing CD4+ T-cell responses. Our data additionally demonstrate stronger boosting of HI titres by WPV following prior infection and support WPV administered as a priming dose irrespective of the follow up vaccine for the second dose. Our findings thus show that compared to SV vaccination, WPV-induced humoral responses are significantly increased in scope and magnitude, advocating WPV vaccination regimens for priming immunologically-naïve individuals and also in the event of a pandemic outbreak.
• Determination of short-chain fatty acids by N,N-dimethylethylenediamine derivatization combined with liquid chromatography/mass spectrometry and their implication in influenza virus infection.
  Divyavani Gowda; Yonghan Li; Siddabasave Gowda B Gowda; Marumi Ohno; Hitoshi Chiba; Shu-Ping Hui
  Analytical and bioanalytical chemistry, 414, 22, 6419, 6430, 2022年07月16日, ［国際誌］
  英語, 研究論文（学術雑誌）
• Inactivated whole influenza virus particle vaccines induce neutralizing antibodies with an increase in immunoglobulin gene subclones of B-lymphocytes in cynomolgus macaques.
  Masanori Shiohara; Saori Suzuki; Shintaro Shichinohe; Hirohito Ishigaki; Misako Nakayama; Naoki Nomura; Masashi Shingai; Toshiki Sekiya; Marumi Ohno; Sayaka Iida; Naoko Kawai; Mamiko Kawahara; Junya Yamagishi; Kimihito Ito; Ryotarou Mitsumata; Tomio Ikeda; Kenji Motokawa; Tomoyoshi Sobue; Hiroshi Kida; Kazumasa Ogasawara; Yasushi Itoh
  Vaccine, 40, 30, 4026, 4037, 2022年06月26日, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）
• Inactivated Whole Virus Particle Influenza Vaccine Induces Anti-Neuraminidase Antibodies That May Contribute to Cross-Protection against Heterologous Virus Infection.
  Chimuka Handabile; Toshiki Sekiya; Naoki Nomura; Marumi Ohno; Tomomi Kawakita; Masashi Shingai; Hiroshi Kida
  Vaccines, 10, 5, 2022年05月19日, ［国際誌］
  英語, 研究論文（学術雑誌）, Despite the use of vaccines, seasonal influenza remains a risk to public health. We previously proposed the inactivated whole virus particle vaccine (WPV) as an alternative to the widely used split vaccine (SV) for the control of seasonal and pandemic influenza based on the superior priming potency of WPV to that of SV. In this study, we further examined and compared the immunological potency of monovalent WPV and SV of A/California/7/2009 (X-179A) (H1N1) pdm09 (CA/09) to generate immune responses against heterologous viruses, A/Singapore/GP1908/2015 (IVR-180) (H1N1) pdm09 (SG/15), and A/duck/Hokkaido/Vac-3/2007 (H5N1) (DH/07) in mice. Following challenge with a lethal dose of heterologous SG/15, lower virus titer in the lungs and milder weight loss were observed in WPV-vaccinated mice than in SV-vaccinated ones. To investigate the factors responsible for the differences in the protective effect against SG/15, the sera of vaccinated mice were analyzed by hemagglutination-inhibition (HI) and neuraminidase-inhibition (NI) assays to evaluate the antibodies induced against viral hemagglutinin (HA) and neuraminidase (NA), respectively. While the two vaccines induced similar levels of HI antibodies against SG/15 after the second vaccination, only WPV-vaccinated mice induced significantly higher titers of NI antibodies against the strain. Furthermore, given the significant elevation of NI antibody titers against DH/07, an H5N1 avian influenza virus, WPV was also demonstrated to induce NA-inhibiting antibodies that recognize NA of divergent strains. This could be explained by the higher conservation of epitopes of NA among strains than for HA. Taking these findings together, NA-specific antibodies induced by WPV may have contributed to better protection from infection with heterologous influenza virus SG/15, compared with SV. The present results indicate that WPV is an effective vaccine for inducing antibodies against both HA and NA of heterologous viruses and may be a useful vaccine to conquer vaccine strain mismatch.
• Leptospira Is an Environmental Bacterium That Grows in Waterlogged Soil.
  Yasutake Yanagihara; Sharon Y A M Villanueva; Naoki Nomura; Marumi Ohno; Toshiki Sekiya; Chimuka Handabile; Masashi Shingai; Hideaki Higashi; Shin-Ichi Yoshida; Toshiyuki Masuzawa; Nina G Gloriani; Mitsumasa Saito; Hiroshi Kida
  Microbiology spectrum, 10, 2, e0215721, American Society for Microbiology, 2022年03月15日, ［国際誌］
  英語, 研究論文（学術雑誌）, Leptospirosis is a zoonotic disease caused by infection with pathogenic leptospires. Consistent with recent studies by other groups, leptospires were isolated from 89 out of 110 (80.9%) soil or water samples from varied locations in the Philippines in our surveillance study, indicating that leptospires might have a life cycle that does not involve animal hosts. However, despite previous work, it has not been confirmed whether leptospires multiply in the soil environment under various experimental conditions. Given the fact that the case number of leptospirosis is increased after flood, we hypothesized that waterlogged soil, which mimics the postflooding environment, could be a suitable condition for growing leptospires. To verify this hypothesis, pathogenic and saprophytic leptospires were seeded in the bottles containing 2.5 times as much water as soil, and bacterial counts in the bottles were measured over time. Pathogenic and saprophytic leptospires were found to increase their number in waterlogged soil but not in water or soil alone. In addition, leptospires were reisolated from soil in closed tubes for as long as 379 days. These results indicate that leptospires are in a resting state in the soil and are able to proliferate with increased water content in the environment. This notion is strongly supported by observations that the case number of leptospirosis is significantly higher in rainy seasons and increased after flood. Therefore, we reached the following conclusion: environmental soil is a potential reservoir of leptospires. IMPORTANCE Since research on Leptospira has focused on pathogenic leptospires, which are supposed to multiply only in animal hosts, the life cycle of saprophytic leptospires has long been a mystery. This study demonstrates that both pathogenic and saprophytic leptospires multiply in the waterlogged soil, which mimics the postflooding environment. The present results potentially explain why leptospirosis frequently occurs after floods. Therefore, environmental soil is a potential reservoir of leptospires and leptospirosis is considered an environment-borne as well as a zoonotic disease. This is a significant report to reveal that leptospires multiply under environmental conditions, and this finding leads us to reconsider the ecology of leptospires.
• Abnormal blood coagulation and kidney damage in aged hamsters infected with severe acute respiratory syndrome coronavirus 2
  Marumi Ohno; Michihito Sasaki; Yasuko Orba; Toshiki Sekiya; Md Abdul Masum; Osamu Ichii; Tatsuya Sawamura; Akemi Kakino; Yasuhiko Suzuki; Hiroshi Kida; Hirofumi Sawa; Masashi Shingai
  Viruses, 13, 11, 2021年11月, ［査読有り］, ［筆頭著者］, ［国際誌］
  英語, 研究論文（学術雑誌）
• Defining the kinetic effects of infection with influenza virus A/PR8/34 (H1N1) on sphingosine-1-phosphate signaling in mice by targeted LC/MS.
  Divyavani Gowda; Marumi Ohno; Siddabasave Gowda B Gowda; Hitoshi Chiba; Masashi Shingai; Hiroshi Kida; Shu-Ping Hui
  Scientific reports, 11, 1, 20161, 20161, 2021年10月11日, ［査読有り］, ［筆頭著者］, ［国際誌］
  英語, 研究論文（学術雑誌）
• Critical role of oxidized LDL receptor-1 in intravascular thrombosis in a severe influenza mouse model.
  Marumi Ohno; Akemi Kakino; Toshiki Sekiya; Naoki Nomura; Masashi Shingai; Tatsuya Sawamura; Hiroshi Kida
  Scientific reports, 11, 1, 15675, 15675, Springer Science and Business Media LLC, 2021年08月03日, ［査読有り］, ［筆頭著者］, ［国際誌］
  英語, 研究論文（学術雑誌）
• Detection and Structural Characterization of SFAHFA Homologous Series in Mouse Colon Contents by LTQ-Orbitrap-MS and Their Implication in Influenza Virus Infection.
  Siddabasave Gowda B Gowda; Divyavani Gowda; Marumi Ohno; Chongsheng Liang; Hitoshi Chiba; Shu-Ping Hui
  Journal of the American Society for Mass Spectrometry, 32, 8, 2196, 2205, 2021年06月25日, ［国際誌］
  英語, 研究論文（学術雑誌）
• Potent priming by inactivated whole influenza virus particle vaccines is linked to viral RNA uptake into antigen presenting cells
  Masashi Shingai; Naoki Nomura; Toshiki Sekiya; Marumi Ohno; Daisuke Fujikura; Chimuka Handabile; Ryosuke Omori; Yuki Ohara; Tomohiro Nishimura; Masafumi Endo; Kazuhiko Kimachi; Ryotarou Mitsumata; Tomio Ikeda; Hiroki Kitayama; Hironori Hatanaka; Tomoyoshi Sobue; Fumihito Muro; Saori Suzuki; Cong Thanh Nguyen; Hirohito Ishigaki; Misako Nakayama; Yuya Mori; Yasushi Itoh; Marios Koutsakos; Brendon Y Chua; Katherine Kedzierska; Lorena E Brown; David C Jackson; Kazumasa Ogasawara; Yoichiro Kino; Hiroshi Kida
  Vaccine, 39, 29, 3940, 3951, Elsevier BV, 2021年06月, ［査読有り］, ［筆頭著者］, ［国際誌］
  英語, 研究論文（学術雑誌）
• Updating the influenza virus library at Hokkaido University -It's potential for the use of pandemic vaccine strain candidates and diagnosis
  Naoki Nomura; Keita Matsuno; Masashi Shingai; Marumi Ohno; Toshiki Sekiya; Ryosuke Omori; Yoshihiro Sakoda; Robert G. Webster; Hiroshi Kida
  Virology, 557, 55, 61, Elsevier BV, 2021年05月, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）
• Immune profiling of influenza‐specific B‐ and T‐cell responses in macaques using flow cytometry‐based assays
  Marios Koutsakos; Toshiki Sekiya; Brendon Y Chua; Thi Hoang Oanh Nguyen; Adam K Wheatley; Jennifer A Juno; Marumi Ohno; Naoki Nomura; Yuki Ohara; Tomohiro Nishimura; Masafumi Endo; Saori Suzuki; Hirohito Ishigaki; Misako Nakayama; Cong T Nguyen; Yasushi Itoh; Masashi Shingai; Kazumasa Ogasawara; Yoichiro Kino; Stephen J Kent; David C Jackson; Lorena E Brown; Hiroshi Kida; Katherine Kedzierska
  Immunology & Cell Biology, 99, 1, 97, 106, Wiley, 2020年09月07日, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）
• Influenza virus infection affects insulin signaling, fatty acid-metabolizing enzyme expressions, and the tricarboxylic acid cycle in mice
  Marumi Ohno; Toshiki Sekiya; Naoki Nomura; Taku ji Daito; Masashi Shingai; Hiroshi Kida
  Scientific Reports, 10, 1, 10879, 10879, Springer Science and Business Media LLC, 2020年06月, ［査読有り］, ［筆頭著者］, ［国際誌］
  英語, 研究論文（学術雑誌）
• Inactivated whole virus particle vaccine with potent immunogenicity and limited IL-6 induction is ideal for influenza
  Toshiki Sekiya; Edin J Mifsud; Marumi Ohno; Naoki Nomura; Mayumi Sasada; Daisuke Fujikura; Takuji Daito; Masashi Shingai; Yuki Ohara; Tomohiro Nishimura; Masafumi Endo; Ryotarou Mitsumata; Tomio Ikeda; Hironori Hatanaka; Hiroki Kitayama; Kenji Motokawa; Tomoyoshi Sobue; Saori Suzuki; Yasushi Itoh; Lorena E Brown; Kazumasa Ogasawara; Yoichiro Kino; Hiroshi Kida
  Vaccine, 37, 15, 2158, 2166, Elsevier BV, 2019年04月, ［査読有り］, ［筆頭著者］, ［国際誌］
  英語, 研究論文（学術雑誌）
• Co-Chaperone-Mediated Suppression of LPS-Induced Cardiac Toxicity Through NFκB Signaling
  Marumi Ohno; Rick Moore; Page Myers; Masahiko Negishi
  SHOCK, 50, 2, 248, 254, Ovid Technologies (Wolters Kluwer Health), 2018年08月, ［査読有り］, ［筆頭著者］, ［国際誌］
  英語, 研究論文（学術雑誌）
• GR Utilizes a Co-Chaperone Cytoplasmic CAR Retention Protein to Form an N/C Interaction
  Marumi Ohno; Masahiko Negishi
  Nuclear Receptor Signaling, 15, 155076291880107, 155076291880107, SAGE Publications, 2018年01月, ［査読有り］, ［筆頭著者］, ［国際誌］
  英語, 研究論文（学術雑誌）
• Strain differences in cytochrome P450 mRNA and protein expression, and enzymatic activity among Sprague Dawley, Wistar, Brown Norway and Dark Agouti rats
  Yoshihiro NISHIYAMA; Shouta M.M. NAKAYAMA; Kensuke P. WATANABE; Yusuke K. KAWAI; Marumi OHNO; Yoshinori IKENAKA; Mayumi ISHIZUKA
  Journal of Veterinary Medical Science, 78, 4, 675, 680, Japanese Society of Veterinary Science, 2016年, ［査読有り］, ［国内誌］
  英語, 研究論文（学術雑誌）
• Metabolic Activation of Heterocyclic Amines and Expression of Xenobiotic-Metabolizing Enzymes in the Gastrointestinal Tract of Rats
  Wageh S. Darwish; Shouta M. M. Nakayama; Yuumi Itotani; Marumi Ohno; Yoshinori Ikenaka; Mayumi Ishizuka
  Journal of Food Science, 80, 7, T1627, T1632, Wiley, 2015年07月, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）
• Nuclear receptor-mediated regulation of cytochrome P450 genes
  Saki Gotoh; Marumi Ohno; Kouichi Yoshinari; Masahiko Negishi; Kaname Kawajiri
  Cytochrome P450: Structure, Mechanism, and Biochemistry, Fourth Edition, 787, 812, 2015年01月01日
  論文集(書籍)内論文
• The Roles of Co-Chaperone CCRP/DNAJC7 in Cyp2b10 Gene Activation and Steatosis Development in Mouse Livers
  Marumi Ohno; Tomohiko Kanayama; Rick Moore; Manas Ray; Masahiko Negishi
  PLoS ONE, 9, 12, e115663, e115663, Public Library of Science (PLoS), 2014年12月26日, ［査読有り］, ［筆頭著者］, ［国際誌］
  英語, 研究論文（学術雑誌）
• Astaxanthin rich crude extract of Haematococcus pluvialis induces cytochrome P450 1A1 mRNA by activating aryl hydrocarbon receptor in rat hepatoma H4IIE cells
  Marumi Ohno; Wageh Sobhy Darwish; Yoshinori Ikenaka; Wataru Miki; Shoichi Fujita; Mayumi Ishizuka
  Food Chemistry, 130, 2, 356, 361, Elsevier BV, 2012年01月, ［査読有り］, ［筆頭著者］
  研究論文（学術雑誌）
• Sudan III dye strongly induces CYP1A1 mRNA expression in HepG2 cells
  Marumi Ohno; Yoshinori Ikenaka; Mayumi Ishizuka
  Journal of Biochemical and Molecular Toxicology, 26, 1, 16, 22, Wiley, 2012年01月, ［査読有り］, ［筆頭著者］, ［国際誌］
  英語, 研究論文（学術雑誌）
• All-trans retinoic acid inhibits the recruitment of ARNT to DNA, resulting in the decrease of CYP1A1 mRNA expression in HepG2 cells
  Marumi Ohno; Yoshinori Ikenaka; Mayumi Ishizuka
  Biochemical and Biophysical Research Communications, 417, 1, 484, 489, Elsevier BV, 2012年01月, ［査読有り］, ［筆頭著者］
  研究論文（学術雑誌）
• Astaxanthin can alter CYP1A-dependent activities via two different mechanisms: Induction of protein expression and inhibition of NADPH P450 reductase dependent electron transfer
  Marumi Ohno; Wageh S. Darwish; Yoshinori Ikenaka; Wataru Miki; Mayumi Ishizuka
  Food and Chemical Toxicology, 49, 6, 1285, 1291, Elsevier BV, 2011年06月, ［査読有り］, ［筆頭著者］
  研究論文（学術雑誌）
• Carotenoids as regulators for inter-species difference in cytochrome P450 1A expression and activity in ungulates and rats
  Wageh S. Darwish; Yoshinori Ikenaka; Marumi Ohno; Elsaid A. Eldaly; Mayumi Ishizuka
  Food and Chemical Toxicology, 48, 11, 3201, 3208, Elsevier BV, 2010年11月, ［査読有り］
  研究論文（学術雑誌）
• Metabolic Activation of Heterocyclic Amines and Expression of CYP1A1 in the Tongue
  Mami Takiguchi; Wageh S. Darwish; Yoshinori Ikenaka; Marumi Ohno; Mayumi Ishizuka
  Toxicological Sciences, 116, 1, 79, 91, Oxford University Press (OUP), 2010年07月, ［査読有り］
  研究論文（学術雑誌）
• Cytochrome P450 1A-Dependent Activities in Deer, Cattle and Horses
  Wageh Sobhy DARWISH; Yoshinori IKENAKA; Elsaid Abozeid ELDALY; Marumi OHNO; Kentaro Q. SAKAMOTO; Shoichi FUJITA; Mayumi ISHIZUKA
  Journal of Veterinary Medical Science, 72, 5, 561, 566, Japanese Society of Veterinary Science, 2010年, ［査読有り］
  研究論文（学術雑誌）
• Crude cacaotheobroma cacaoextract reduces mutagenicity induced by benzo[a]pyrene through inhibition of CYP1A activityin vitro
  Marumi Ohno; Kentaro Q Sakamoto; Mayumi Ishizuka; Shoichi Fujita
  Phytotherapy Research, 23, 8, 1134, 1139, Wiley, 2009年08月, ［査読有り］, ［筆頭著者］
  研究論文（学術雑誌）

• Selecting and using the appropriate influenza vaccine for each individual
  Toshiki Sekiya; Marumi Ohno; Naoki Nomura; Chimuka Handabile; Masashi Shingai; David C. Jackson; Lorena E. Brown; Hiroshi Kida, Viruses, 13, 6, 2021年06月, ［国際誌］
  英語
• インフルエンザウイルスライブラリーを活用したパンデミックインフルエンザ対策
  野村直樹; 新開大史; 松野啓太; 関屋俊輝; 関屋俊輝; 大野円実; 磯田典和; 迫田義博; 喜田宏; 喜田宏, 日本獣医学会学術集会講演要旨集, 164th (CD-ROM), 2021年
• 不活化インフルエンザウイルス全粒子ワクチンの非臨床試験
  新開大史; 新開大史; 野村直樹; 関屋俊輝; 関屋俊輝; 大野円実; 笹田万友美; 大東卓史; 鈴木紗織; 石垣宏仁; 伊藤靖; 小笠原一誠; 小笠原一誠; 喜田宏; 喜田宏; 喜田宏, 日本ワクチン学会学術集会プログラム・抄録集, 22nd, 2018年
• 鳥類における薬物代謝の特徴:ピレンをモデル化合物として
  河田みなみ; 池中良徳; 渡邉研右; AKSORN Saengtienchai; 大野円実; 石塚真由美, 日本獣医学会学術集会講演要旨集, 154th, 2012年
• 鳥類におけるI相およびII相反応の特徴と種差
  河田みなみ; 池中良徳; 渡邉研右; 大野円実; 上田春樹; 西山義広; 石塚真由美, 日本獣医学会学術集会講演要旨集, 153rd, 2012年
• ラットにおけるシトクロムP450の系統差
  西山義広; 池中良徳; 大野円実; 渡邊研右; 川合佑典; 中山翔太; 田中和之; 石塚真由美, 日本獣医学会学術集会講演要旨集, 152nd, 2011年
• ラットの消化管における異物代謝酵素の発現パターン
  糸谷悠美; 池中良徳; 大野円実; 中山翔太; WAGEH Sobhy; 石塚真由美, 日本獣医学会学術集会講演要旨集, 151st, 2011年
• Rattus属における薬物代謝能とシトクロムP450の種差・系統差
  西山義広; 田中和之; 大野円実; 渡邊研右; 川合佑典; 中山翔太; 谷川力; 春成常仁; 池中良徳; 石塚真由美, 日本獣医学会学術集会講演要旨集, 151st, 2011年
• ラットの消化管における異物代謝酵素の比較
  糸谷悠美; 池中良徳; 大野円実; 中山翔太; SOBHY Wageh; 石塚真由美, 日本獣医学会学術集会講演要旨集, 152nd, 2011年
• 舌に発現するシトクロムP450
  滝口真美; 安東志麻; 大野円実; 坂本健太郎; 石塚真由美, 日本獣医学会学術集会講演要旨集, 147th, 2009年
• カカオマス製品の粗抽出液の抗変異原作用
  大野円実; 坂本健太郎; 石塚真由美; 藤田正一, 日本獣医学会学術集会講演要旨集, 145th, 2008年
• アスタキサンチンの経口投与による薬物代謝酵素活性の誘導機構についての検討
  大野円実; 坂本健太郎; 南大介; 石塚真由美; 藤田正一, 日本獣医学会学術集会講演要旨集, 146th, 2008年

• Lipid Metabolism and Infectious Diseases
  Marumi Ohno
  Sakura Science Program Inauguration and IJSSTE (Hokkaido) Science Seminar, 2024年12月10日, 英語
  45249595;45085772, ［招待講演］
• 異物と生体応答 〜化学物質から病原体まで〜
  大野 円実
  第6回バイオメディカルリサーチ寄附講座セミナー, 2024年10月25日
  45249595;45085772, ［招待講演］

• 宿主因子の制御による重症インフルエンザの新規治療法の研究開発
  科学研究費助成事業
  2021年04月01日 - 2024年03月31日
  大野 円実
  インフルエンザウイルスPR8株を用いた重症インフルエンザマウスモデルにおいて、感染3日目に血管及び肺でLectin-like oxidized LDL receptor-1 (LOX-1)遺伝子発現量が有意に上昇することを見出した。LOX-1は動脈硬化症における病的血液凝固の促進因子であることから、重症インフルエンザによる血液凝固異常においてもLOX-1が関与すると予想された。そこで、野生型マウスとLOX-1ノックアウト（KO）マウスを用いて感染実験を行ったところ、野生型マウスでは感染6日目においてプロトロンビン時間の延長、血中プロトロンビンフラグメント1+2の増加、肺血管内フィブリン析出が観察されたが、KOマウスではこれらの所見が見られなかった。さらに、COVID-19ハムスターモデルおいても肺や血管においてLOX-1の発現量上昇が見られたことから、LOX-1が多様なウイルス感染症において血液凝固異常を引き起こす可能性が示唆された。野生型マウスとKOマウスにPR8株を感染させ、血漿メタボローム解析を行ったところ、KOマウスでは梗塞ダメージマーカー（xanthine及びhypoxanthine濃度）、アミノ酸代謝異常マーカー（フェニルアラニン/チロシン比）、酸化ストレスマーカー（2-aminobutyric acid）の改善が見られた。
  また、PR8株を重症及び非重症条件でマウスに感染させ、感染1、3、6日目に回収した血漿を用いてリピドーム解析を行い、重症インフルエンザに特徴的な脂質代謝変化パターンを明らかにした。重症条件に特徴的な変化として、sn-2位にアラキドン酸を含むホスホジエタノールアミンなどのリン脂質が感染3日目に血中で増加することがわかった。これらの結果は、脂質及びその過酸化代謝物がインフルエンザの重症化に関与している可能性を示唆するものである。
  日本学術振興会, 基盤研究(B), 北海道大学, 21H02376
• インフルエンザ重症化に関与する宿主因子の探索
  科学研究費助成事業
  2017年04月01日 - 2020年03月31日
  大野 円実
  インフルエンザウイルスをマウスに実験感染させエネルギー代謝への影響を調べた。インスリン投与によるAktリン酸化を指標にしたインスリン感受性を評価したところ、感染マウスの肝臓はインスリン感受性の低下を示した。また、グルコース負荷試験により、感染マウスは糖利用能が低下していることが示唆された。これらの結果はインフルエンザウイルス感染によりエネルギー代謝障害が引き起こされることを示している。
  日本学術振興会, 若手研究(B), 北海道大学, 17K15367
• 宿主因子を標的とする新規インフルエンザ治療薬の研究開発
  イノベーション創出研究支援事業（スタートアップ補助金）
  2018年08月 - 2019年03月
  ノーステック財団
• Ah受容体による遺伝子転写調節と慨日リズムの新たな相互作用の解明
  科学研究費助成事業
  2010年 - 2012年
  大野 円実
  転写調節因子アリルハイドロカーボン受容体(AHR)は、パートナータンパク質であるAHR nuclear translocator (ARNT)と2量体を形成し、異物代謝酵素であるシトクロムP450(CYP)1A1などの転写調節を行う。私はこれまでに、オールトランスレチノイン酸がAHR/ARNTの転写調節を抑制することを明らかにしてきた。さらに、今年度はAHR自身の転写調節を行う因子としてRetinoic acid receptor-related orphan receptor α(RORα)を初めて見出した。
  過去の報告から、AHRの発現量は発育段階や組織ごとに異なることや概日リズムを示すことが知られてきた。しかしながらAHR自身の転写調節機構についての研究は少なく、詳細は明らかになっていなかった。私は、ヒトAHRの転写開始点から約500bp上流にROR反応領域(RORE)が存在することを見出した。さらにsiRNAによりRORαをノックダウンすることでAHRのmRNA発現量が3。6倍に増加した。またAHR上流の配列を用いたレポーターアッセイを行ったところ、ROREの欠損または変異によってレポーター活性が増大した。これらのことから、RORαはROREを介してAHRの転写を抑制する因子であることが示唆された。
  RORαは、AHRの示すさまざまな発現パターンを制御する因子の候補となりうると考えられる。本研究は、いまだ不明なAHRの生理的作用についてさらなる理解を深めるのに大きく貢献すると考える。
  日本学術振興会, 特別研究員奨励費, 北海道大学, 10J05187
• カロテノイドによる薬物代謝酵素シトクロムP450誘導における分子基盤の解明
  大学院博士課程＜後期＞奨学金
  2009年04月 - 2010年03月
  三島海雲記念財団