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Affiliation |
Graduate School of Medicine Comprehensive Center for Infectious Disease Control |
ZHANG Tianli
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Research Interests 【 display / non-display 】
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Inflammatory responses
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Sulfur biology
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Micribiology
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redox
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Immune responses
Graduating School 【 display / non-display 】
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-2011.07
Jiujiang University Faculty of Medicine Graduated
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2015.04-2019.03
Kumamoto University Graduate School of Medical Sciences Department of Microbiology Graduated
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2013.04-2015.03
Kumamoto University Graduate School of Medical Sciences Department of Immunology Graduated
Graduate School 【 display / non-display 】
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2015.04-2019.03
Kumamoto University Graduate School, Division of Medicine Doctor's Course Completed
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2013.04-2015.03
Kumamoto University Graduate School, Division of Medicine Master's Course Completed
Campus Career 【 display / non-display 】
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2025.04-Now
Akita University Graduate School of Medicine Comprehensive Center for Infectious Disease Control Assistant Professor
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2024.06-2025.03
Akita University Center for Integrated Control, Epidemiology and Molecular Pathophysiology of Infectious Diseases Assistant Professor
External Career 【 display / non-display 】
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2024.06
Akita University Center for Integrated Control, Epidemiology and Molecular Pathophysiology of Infectious Diseases Assistant Professor
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2022.10-2024.05
Kumamoto University Faculty of Life Sciences
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2020.10-2022.09
Japan Society for the Promotion of Science
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2019.04-2020.09
Kumamoto University Faculty of Life Sciences
Research Areas 【 display / non-display 】
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Life Science / Medical biochemistry
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Life Science / Immunology
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Life Science / Immunology
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Life Science / Medical biochemistry
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Life Science / Bacteriology
Research Achievements 【 display / non-display 】
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Xiaoyan Li, Touya Toyomoto, Tianli Zhang, Chunyu Guo, Stephen Lindahl, Hiroyasu Tsutsuki, Ming Xian, Tomohiro Sawa
International immunology ( Oxford University Press (OUP) ) 36 ( 12 ) 641 - 652 2024.06
Research paper (journal)
Interferons (IFNs) are cytokines produced and secreted by immune cells when viruses, tumor cells, and so forth, invade the body. Their biological effects are diverse, including antiviral, cell growth-inhibiting, and antitumor effects. The main subclasses of interferons include type-I (e.g., IFN-α and IFN-β) and type-II (IFN-γ), which activate intracellular signals by binding to type-I and type-II IFN receptors, respectively. We have previously shown that when macrophages are treated with supersulfide donors, which have polysulfide structures in which three or more sulfur atoms are linked within the molecules, IFN-β-induced cellular responses, including signal transducer and activator of transcription 1 (STAT1) phosphorylation and inducible nitric oxide synthase (iNOS) expression, were strongly suppressed. However, the subfamily specificity of the suppression of IFN signals by supersulfides and the mechanism of this suppression are unknown. This study demonstrated that supersulfide donor N-acetyl-L-cysteine tetrasulfide (NAC-S2) can inhibit IFN signaling in macrophages stimulated not only with IFN-α/β but also with IFN-γ. Our data suggest that NAC-S2 blocks phosphorylation of Janus kinases (JAKs), thereby contributes to the inhibition of phosphorylation of STAT1. Under the current experimental conditions, hydrogen sulfide (H2S) donor NaHS failed to inhibit IFN signaling. Similar to NAC-S2, carbohydrate-based supersulfide donor thioglucose tetrasulfide (TGS4) was capable of strongly inhibiting tumor necrosis factor-αproduction, iNOS expression, and nitric oxide production from macrophages stimulated with lipopolysaccharide. Further understanding of molecular mechanisms how supersulfide donors exhibit their inhibitory actions towards JAK/STAT signaling is necessary basis for development of supersulfide-based therapeutic strategy against autoimmune disorders with dysregulated IFN signaling.
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Regulation of innate immune and inflammatory responses by supersulfides.
Hiroyasu Tsutsuki, Tianli Zhang, Takaaki Akaike, Tomohiro Sawa
International immunology ( Oxford University Press (OUP) ) 36 ( 4 ) 143 - 154 2024.01 [Refereed]
Research paper (journal)
Innate immunity plays an important role in host defense against microbial infections. It also participates in activation of acquired immunity through cytokine production and antigen presentation. Pattern recognition receptors such as Toll-like receptors and nucleotide oligomerization domain-like receptors sense invading pathogens and associated tissue injury, after which inflammatory mediators such as pro-inflammatory cytokines and nitric oxide are induced. Supersulfides are molecular species possessing catenated sulfur atoms such as persulfide and polysulfide moieties. They have recently been recognized as important regulators in cellular redox homeostasis by acting as potent antioxidants and nucleophiles. In addition, recent studies suggested that supersulfides are critically involved in the regulation of innate immune and inflammatory responses. In this review, we summarize current knowledge of the chemistry and biology of supersulfides, with particular attention to their roles in regulation of innate immune and inflammatory responses. Studies with animal models of infection and inflammation demonstrated the potent anti-inflammatory functions of supersulfides such as blocking pro-inflammatory signaling cascades, reducing oxidative stresses, and inhibiting replication of microbial pathogens including severe acute respiratory syndrome coronavirus 2. Precise understanding of how supersulfides regulate innate immune responses is the necessary requirement for developing supersulfide-based diagnostic as well as therapeutic strategies against inflammatory disorders.
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Thioglucose-derived tetrasulfide, a unique polysulfide model compound.
Stephen Lindahl, Meg Shieh, Tianli Zhang, Chunyu Guo, Jerome R Robinson, Tomohiro Sawa, Ming Xian
Redox biology 70 103045 - 103045 2024.01 [Refereed]
Research paper (journal)
Polysulfides have received increased interest in redox biology due to their role as the precursors of H2S and persulfides. However, the compounds that are suitable for biological investigations are limited to cysteine- and glutathione-derived polysulfides. In this work, we report the preparation and evaluation of a novel polysulfide derived from thioglucose, which represents the first carbohydrate-based polysulfide. This compound, thioglucose tetrasulfide (TGS4), showed excellent stability and water solubility. H2S and persulfide production from TGS4, as well as its associated antioxidative property were also demonstrated. Additionally, TGS4 was demonstrated to significantly induce cellular sulfane sulfur level increase, in particular for the formation of hydropersulfides/trisulfides. These results suggest that TGS4 is a useful tool for polysulfide research.
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Redox Biology Involved in the Toxicity of Enterohemorrhagic <i>Escherichia coli</i> Toxin SubAB
Tsutsuki Hiroyasu, Zhang Tianli, Sawa Tomohiro
YAKUGAKU ZASSHI ( The Pharmaceutical Society of Japan ) 144 ( 1 ) 57 - 60 2024.01
Research paper (journal)
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Redox Regulation of Xenobiotics by Reactive Sulfur and Supersulfide Species.
Tianli Zhang, Takaaki Akaike, Tomohiro Sawa
Antioxidants & redox signaling ( Mary Ann Liebert Inc ) 40 ( 10-12 ) 679 - 690 2023.09 [Refereed]
Research paper (journal)
Significance: Routine exposure to xenobiotics is unavoidable during our lifetimes. Certain xenobiotics are hazardous to human health, and are metabolized in the body to render them less toxic. During this process, several detoxification enzymes cooperatively metabolize xenobiotics. Glutathione (GSH) conjugation plays an important role in the metabolism of electrophilic xenobiotics. Recent Advances: Recent advances in reactive sulfur and supersulfide (RSS) analyses showed that persulfides and polysulfides bound to low-molecular-weight thiols, such as GSH, and to protein thiols are abundant in both eukaryotes and prokaryotes. The highly nucleophilic nature of hydropersulfides and hydropolysulfides contributes to cell protection against oxidative stress and electrophilic stress. Critical Issues: In contrast to GSH conjugation to electrophiles that is aided by glutathione S-transferase (GST), persulfides and polysulfides can directly form conjugates with electrophiles without the catalytic actions of GST. The polysulfur bonds in the conjugates are further reduced by perthioanions and polythioanions derived from RSS to form sulfhydrated metabolites that are no longer electrophilic but rather nucleophilic, and differ from metabolites that are formed via GSH conjugation. Future Directions: In view of the abundance of RSS in cells and tissues, metabolism of xenobiotics that is mediated by RSS warrants additional investigations, such as studies of the impact of microbiota-derived RSS on xenobiotic metabolism. Metabolites formed from reactions between electrophiles and RSS may be potential biomarkers for monitoring exposure to electrophiles and for studying their metabolism by RSS.
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Identification of endogenous methylation products of cysteine, homocysteine, and glutathione persulfides in bacteria, plants, and mammalian cells
SAWA Tomohiro, TOYOMOTO Touya, ZHANG Tianli
Annual Meeting of the Japanese Society of Toxicology ( The Japanese Society of Toxicology ) 52.1 ( 0 ) O-30 2025
<p>Biological methylation of thiol containing molecules occurs in various processes including biosynthesis of methionine via homocysteine methylation. Occurrence of methylation products of cysteine and glutathione have been determined in procaryotes and eukaryotes. We have reported that low-molecular weight thiols including cysteine, homocysteine, and glutathione are existent in cells as persulfides and polysulfides. It is noteworthy that per/polysulfidation make thiol molecules more nucleophilic, antioxidative, and anti-inflammatory. Methylation products of cysteine-based per/polysulfides are not determined yet, however.In this study, we developed analytical method that enabled us to quantitate methylation products of cysteine-based persulfides in various biological samples. S-Methylated persulfide derivatives of cysteine (S-MeS-Cys), homocysteine (S-MeS-HCys), and glutathione (S-MeS-SG) were prepared as standards. Precise identification and quantification of those species can be achieved by means of tandem-mass spectrometry. By using this method, we could successfully identify S-MeS-SG in bacteria, cultured cells, and mouse tissues. In garlic clove, levels of S-MeS-SG was greatly higher than native glutathione. S-MeS-SG was resistance against oxidation by hydrogen peroxide and reduction by glutathione reductase. It is thus speculated that metabolic regulation of S-MeS-SG differ from those of glutathione and its oxidized form (GSSG). Our study warrants further investigations on the biological functions and the mechanisms of productions of methylated persulfide products.</p>
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カルバペネム耐性菌に対抗するキレート剤をベースとした新規MBL阻害剤の開発(Development of chelator based novel MBL inhibitors to combat carbapenem resistance bacteria)
豊元 柊弥, 張 田力, 上釜 綾夏, 津々木 博康, 澤 智裕
日本細菌学雑誌 ( 日本細菌学会 ) 79 ( 2 ) 119 - 119 2024.06
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肺炎球菌感染症はマウス腎臓において硫黄代謝物の特異的欠乏を引き起こす(Streptococcus pneumonia infection induced kidney specific depletion of sulfur metabolites in mice)
Azizur Rahman, 張 田力, 津々木 博康, 豊元 柊弥, 澤 智裕
日本細菌学雑誌 ( 日本細菌学会 ) 79 ( 2 ) 153 - 153 2024.06
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Breathomics for respiratory viral infection.
松永哲郎, ZHANG Tianli, 赤池孝章, 赤池孝章
月刊臨床免疫・アレルギー科 82 ( 3 ) 2024
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Anti-inflammatory effects of supersulfides
Tsutsuki Hiroyasu, Zhang Tianli, Sawa Tomohiro
93 ( 5 ) 666 - 673 2021.10
◆Original paper【 display / non-display 】
◆Other【 display / non-display 】
Grant-in-Aid for Scientific Research 【 display / non-display 】
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Molecular mechanisms of glutathione transport-dependent regulation of NLRP3 inflammasome
Grant-in-Aid for JSPS Fellows
Project Year： 2020.11 - 2023.03
Presentations 【 display / non-display 】
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Supersulfides regulate NLRP3 inflammasome activation through sensing homeostasis
Tianli Zhang
The 11th Biennial Meeting of Society for Free Radical Research-Asia 2024.10 - 2024.10
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Potentiation of antibacterial effect of macrophages by polysulfide donor treatement
Tianli Zhang
2018.09 - 2018.09