Updated on 2022/05/18

写真a

 
AKATSUKA, Shinya
 
Organization
Graduate School of Medicine Program in Integrated Medicine Pathology Lecturer
Graduate School
Graduate School of Medicine
Undergraduate School
School of Medicine
Title
Lecturer
Contact information
メールアドレス

Degree 2

  1. 工学修士 ( 1993.3   慶應義塾大学 ) 

  2. Ph.D. in Medicine ( 2007.3   Kyoto University ) 

Research Areas 2

  1. Life Science / Experimental pathology

  2. Life Science / Laboratory animal science

Current Research Project and SDGs 1

  1. Analysis of distribution dynamics of DNA damage and mutation in the genome during carcinogenesis

Research History 3

  1. 名古屋大学医学系研究科 分子病理診断学 講師

    2012.11

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    Country:Japan

  2. 名古屋大学医学系研究科 分子病理診断学 助教

    2008.7 - 2012.10

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    Country:Japan

  3. 日本電気株式会社(NEC)

    1993.4 - 2001.1

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    Country:Japan

Education 3

  1. Kyoto University   Graduate School, Division of Medicine

    2002.4 - 2006.3

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    Country: Japan

  2. Keio University   Graduate School, Division of Science and Engineering

    1991.4 - 1993.3

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    Country: Japan

  3. Keio University   Faculty of Science and Engineering

    1987.4 - 1991.3

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    Country: Japan

 

Papers 56

  1. Ferroptosis resistance determines high susceptibility of murine A/J strain to iron-induced renal carcinogenesis. Reviewed

    Cheng Z, Akatsuka S, Li GH, Mori K, Takahashi T, Toyokuni S

    Cancer science   Vol. 113 ( 1 ) page: 65 - 78   2022.1

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    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1111/cas.15175

    PubMed

  2. Augmented oxidative stress increases 8-oxoguanine preferentially in the transcriptionally active genomic regions.

    Akatsuka S, Li GH, Kawaguchi S, Takahashi T, Yoshihara M, Suyama M, Toyokuni S

    Free radical research   Vol. 54 ( 11-12 ) page: 872 - 882   2020.12

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    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1080/10715762.2020.1733548

    PubMed

  3. Prognostic significance of the MDM2/HMGA2 ratio and histological tumor grade in dedifferentiated liposarcoma.

    Yamashita K, Kohashi K, Yamada Y, Akatsuka S, Ikuta K, Nishida Y, Toyokuni S, Oda Y

    Genes, chromosomes & cancer   Vol. 60 ( 1 ) page: 26 - 37   2021.1

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    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1002/gcc.22899

    PubMed

  4. Defective biosynthesis of ascorbic acid in Sod1-deficient mice results in lethal damage to lung tissue.

    Homma T, Takeda Y, Nakano T, Akatsuka S, Kinoshita D, Kurahashi T, Saitoh S, Yamada KI, Miyata S, Asao H, Goto K, Watanabe T, Watanabe M, Toyokuni S, Fujii J

    Free radical biology & medicine   Vol. 162   page: 255 - 265   2021.1

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    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1016/j.freeradbiomed.2020.10.023

    PubMed

  5. Carcinogenesis as Side Effects of Iron and Oxygen Utilization: From the Unveiled Truth toward Ultimate Bioengineering.

    Toyokuni S, Kong Y, Cheng Z, Sato K, Hayashi S, Ito F, Jiang L, Yanatori I, Okazaki Y, Akatsuka S

    Cancers   Vol. 12 ( 11 )   2020.11

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    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.3390/cancers12113320

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  6. Novel ovarian endometriosis model causes infertility via iron-mediated oxidative stress in mice.

    Hayashi S, Nakamura T, Motooka Y, Ito F, Jiang L, Akatsuka S, Iwase A, Kajiyama H, Kikkawa F, Toyokuni S

    Redox biology   Vol. 37   page: 101726   2020.10

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    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1016/j.redox.2020.101726

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  7. Asbestos conceives Fe(II)-dependent mutagenic stromal milieu through ceaseless macrophage ferroptosis and β-catenin induction in mesothelium.

    Ito F, Yanatori I, Maeda Y, Nimura K, Ito S, Hirayama T, Nagasawa H, Kohyama N, Okazaki Y, Akatsuka S, Toyokuni S

    Redox biology   Vol. 36   page: 101616   2020.9

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    DOI: 10.1016/j.redox.2020.101616

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  8. Overexpression of miR-199/214 is a distinctive feature of iron-induced and asbestos-induced sarcomatoid mesothelioma in rats.

    Okazaki Y, Chew SH, Nagai H, Yamashita Y, Ohara H, Jiang L, Akatsuka S, Takahashi T, Toyokuni S

    Cancer science   Vol. 111 ( 6 ) page: 2016 - 2027   2020.6

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    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1111/cas.14405

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  9. Frequent homozygous deletion of Cdkn2a/2b in tremolite-induced malignant mesothelioma in rats.

    Okazaki Y, Misawa N, Akatsuka S, Kohyama N, Sekido Y, Takahashi T, Toyokuni S

    Cancer science   Vol. 111 ( 4 ) page: 1180 - 1192   2020.4

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    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1111/cas.14358

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  10. <i>Mth1</i> deficiency provides longer survival upon intraperitoneal crocidolite injection in female mice.

    Funahashi S, Okazaki Y, Akatsuka S, Takahashi T, Sakumi K, Nakabeppu Y, Toyokuni S

    Free radical research   Vol. 54 ( 2-3 ) page: 195 - 205   2020.3

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    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1080/10715762.2020.1743285

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  11. Superiority of rat over murine model for studies on the evolution of cancer genome

    Akatsuka S, Li GH, Toyokuni S.

    Free Radic Res.   Vol. 52 ( 11-12 ) page: 1323 - 1327   2018.12

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    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1080/10715762.2018.1467562

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  12. Expression of P-REX2a is associated with poor prognosis in endometrial malignancies. Reviewed

    Takeshita S, Yamashita Y, Shiomi K, Suzuki N, Yoshida J, Naiki-Ito A, Suzuki S, Akatsuka S, Toyokuni S, Takahashi T, Mase S, Arakawa A, Sugiura-Ogasawara M, Takahashi S

    Oncotarget   Vol. 9 ( 37 ) page: 24778-24786   2018.5

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    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.18632/oncotarget.25349

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  13. Fenton reaction-induced renal carcinogenesis in Mutyh-deficient mice exhibits less chromosomal aberrations than the rat model.

    Li GH, Akatsuka S, Chew SH, Jiang L, Nishiyama T, Sakamoto A, Takahashi T, Futakuchi M, Suzuki H, Sakumi K, Nakabeppu Y, Toyokuni S.

    Pathol Int.   Vol. 67 ( 11 ) page: 564 - 574   2017.11

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    DOI: 10.1111/pin.12598

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  14. Iron and thiol redox signaling in cancer: An exquisite balance to escape ferroptosis.

    Toyokuni S, Ito F, Yamashita K, Okazaki Y, Akatsuka S.

    Free Radic Biol Med.   Vol. 108   page: 610 - 626   2017.7

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    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1016/j.freeradbiomed.2017.04.024

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  15. Rheostatic CD44 isoform expression and its association with oxidative stress in human malignant mesothelioma.

    Chew SH, Okazaki Y, Akatsuka S, Wang S, Jiang L, Ohara Y, Ito F, Saya H, Sekido Y, Toyokuni S

    Free radical biology & medicine   Vol. 106   page: 91 - 99   2017.5

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    DOI: 10.1016/j.freeradbiomed.2017.02.011

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  16. Rheostatic CD44 isoform expression and its association with oxidative stress in human malignant mesothelioma. Reviewed

    Chew SH, Okazaki Y, Akatsuka S, Wang S, Jiang L, Ohara Y, Ito F, Saya H, Sekido Y, Toyokuni S.

    Free Radic Biol Med   Vol. 106   page: 91-99   2017.2

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  17. Urokinase-type plasminogen activator receptor promotes proliferation and invasion with reduced cisplatin sensitivity in malignant mesothelioma. Reviewed

    Wang S, Jiang L, Han Y, Chew SH, Ohara Y, Akatsuka S, Weng L, Kawaguchi K, Fukui T, Sekido Y, Yokoi K, Toyokuni S.

    Oncotarget   Vol. 7 ( 43 ) page: 69565-69578   2016.10

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  18. Dual preventive benefits of iron elimination by desferal in asbestos-induced mesothelial carcinogenesis. Reviewed

    Jiang L, Chew SH, Nakamura K, Ohara Y, Akatsuka S, Toyokuni S.

    Cancer Sci   Vol. 107 ( 7 ) page: 908-915   2016.7

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  19. Pain-reducing anesthesia prevents oxidative stress in human term placenta. Reviewed

    Tsuzuki Y, Yamashita Y, Hattori Y, Li GH, Akatsuka S, Kotani T, Kikkawa F, Naiki-Ito A, Takahashi S, Nishiwaki K, Toyokuni S.

    J Clin Biochem Nutr   Vol. 58 ( 2 ) page: 156-160   2016.3

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  20. Genome-wide Profiling of 8-Oxoguanine Reveals Its Association with Spatial Positioning in Nucleus. Reviewed

    Yoshihara M, Jiang L, Akatsuka S, Suyama M, Toyokuni S.

    DNA Res.   Vol. 21 ( 6 ) page: 603-612   2014.12

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  21. Connective tissue growth factor and β-catenin constitute an autocrine loop for activation in rat sarcomatoid mesothelioma. Reviewed

    Jiang L, Yamashita Y, Chew SH, Akatsuka S, Ukai S, Wang S, Nagai H, Okazaki Y, Takahashi T, Toyokuni S.

    J Pathol.   Vol. 233 ( 4 ) page: 402-414   2014.8

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  22. Expression of chromobox homolog 7 (CBX7) is associated with poor prognosis in ovarian clear cell adenocarcinoma via TRAIL-induced apoptotic pathway regulation. Reviewed

    Shinjo K, Yamashita Y, Yamamoto E, Akatsuka S, Uno N, Kamiya A, Niimi K, Sakaguchi Y, Nagasaka T, Takahashi T, Shibata K, Kajiyama H, Kikkawa F, Toyokuni S.

    Int J Cancer.   Vol. 135 ( 2 ) page: 308-218   2014.7

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  23. Cancer-promoting role of adipocytes in asbestos-induced mesothelial carcinogenesis through dysregulated adipocytokine production. Reviewed

    Chew SH, Okazaki Y, Nagai H, Misawa N, Akatsuka S, Yamashita K, Jiang L, Yamashita Y, Noguchi M, Hosoda K, Sekido Y, Takahashi T, Toyokuni S.

    Carcinogenesis   Vol. 35 ( 1 ) page: 164-172   2014.1

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  24. Met is the most frequently amplified gene in endometriosis-associated ovarian clear cell adenocarcinoma and correlates with worsened prognosis. Reviewed

    Yamashita Y, Akatsuka S, Shinjo K, Yatabe Y, Kobayashi H, Seko H, Kajiyama H, Kikkawa F, Takahashi T, Toyokuni S.

    PLoS One   Vol. 8 ( 3 ) page: e57724   2013.3

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  25. Metamorphosis of mesothelial cells with active horizontal motility in tissue culture. Reviewed

    Nagai H, Chew SH, Okazaki Y, Funahashi S, Namba T, Kato T, Enomoto A, Jiang L, Akatsuka S, Toyokuni S.

    Sci Rep   Vol. 3   page: 1144   2013.1

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  26. Iron overload signature in chrysotile-induced malignant mesothelioma. Reviewed

    Jiang L, Akatsuka S, Nagai H, Chew SH, Ohara H, Okazaki Y, Yamashita Y, Yoshikawa Y, Yasui H, Ikuta K, Sasaki K, Kohgo Y, Hirano S, Shinohara Y, Kohyama N, Takahashi T, Toyokuni S.

    J Pathol   Vol. 228 ( 3 ) page: 366-377   2012.11

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  27. Fenton reaction induced cancer in wild type rats recapitulates genomic alterations observed in human cancer. Reviewed

    Akatsuka S, Yamashita Y, Ohara H, Liu YT, Izumiya M, Abe K, Ochiai M, Jiang L, Nagai H, Okazaki Y, Murakami H, Sekido Y, Arai E, Kanai Y, Hino O, Takahashi T, Nakagama H, Toyokuni S.

    PLoS One   Vol. 7 ( 8 ) page: e43403   2012.8

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  28. The ferroimmunomodulatory role of ectopic endometriotic stromal cells in ovarian endometriosis. Reviewed

    Kobayashi H, Yamashita Y, Iwase A, Yoshikawa Y, Yasui H, Kawai Y, Uchida K, Uno N, Akatsuka S, Takahashi T, Kikkawa F, Toyokuni S.

    Fertil Steril   Vol. 98 ( 2 ) page: 415-422   2012.8

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  29. Genome-wide assessment of oxidatively generated DNA damage. Invited Reviewed

    Akatsuka S, Toyokuni S.

    Free Radic Res   Vol. 46 ( 4 ) page: 523-530   2012.4

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  30. Diameter and rigidity of multiwalled carbon nanotubes are critical factors in mesothelial injury and carcinogenesis. Reviewed

    Nagai H, Okazaki Y, Chew SH, Misawa N, Yamashita Y, Akatsuka S, Ishihara T, Yamashita K, Yoshikawa Y, Yasui H, Jiang L, Ohara H, Takahashi T, Ichihara G, Kostarelos K, Miyata Y, Shinohara H, Toyokuni S.

    Proc Natl Acad Sci U S A.   Vol. 108 ( 49 ) page: E1330-E1338   2011.12

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  31. Free calvarial periosteum graft vascularized by an omental flap in a rat model. Reviewed

    Nakazato K, Toriyama K, Hishida M, Takanari K, Yagi S, Yamashita Y, Akatsuka S, Hayakawa A, Kamei Y.

    Ann Plast Surg   Vol. 67 ( 6 ) page: 649-654   2011.12

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  32. Age- and sun exposure-dependent differences in 8-hydroxy-2'-deoxyguanosine and N-(carboxymethyl)lysine in human epidermis. Reviewed

    Toyokuni S, Hirao A, Wada T, Nagai R, Date A, Yoshii T, Akatsuka S, Yamashita Y, Kawada A.

    J Clin Biochem Nutr   Vol. 49 ( 2 ) page: 121-124   2011.9

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  33. XCR1 expression and biased VH gene usage are distinct features of diffuse large B-cell lymphoma initially manifesting in the bone marrow. Reviewed

    Yamashita Y, Kajiura D, Tang L, Hasegawa Y, Kinoshita T, Nakamura S, Akatsuka S, Toyokuni S, Mori N.

    Am J Clin Pathol   Vol. 135 ( 4 ) page: 556-564   2011.4

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  34. LATS2 Is a Tumor Suppressor Gene of Malignant Mesothelioma Reviewed

    Murakami H, Mizuno T, Taniguchi T, Fujii M, Ishiguro F, Fukui T, Akatsuka S, Horio Y, Hida T, Kondo Y, Toyokuni S, Osada H, Sekido Y.

    Cancer Res.   Vol. 71 ( 3 ) page: 873-883   2011.2

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  35. Stage-specific roles of fibulin-5 during oxidative stress-induced renal carcinogenesis in rats Reviewed

    Ohara H, Akatsuka S, Nagai H, Liu YT, Jiang L, Okazaki Y, Yamashita Y, Nakamura T, Toyokuni S.

    Free Radic Res   Vol. 45 ( 2 ) page: 211-220   2011.2

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  36. Genome-scale approaches to investigate oxidative DNA damage Reviewed

    Akatsuka S, Toyokuni S.

    J Clin Biochem Nutr   Vol. 47 ( 2 ) page: 91-97   2010.9

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  37. Suppression of SLC11A2 expression is essential to maintain duodenal integrity during dietary iron overload Reviewed

    Shirase T, Mori K, Okazaki Y, Itoh K, Yamamoto M, Tabuchi M, Kishi F, Jiang L, Akatsuka S, Nakao K, Toyokuni S.

    Am J Pathol   Vol. 177 ( 2 ) page: 677-685   2010.8

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  38. Homozygous deletion of CDKN2A/2B is a hallmark of iron-induced high-grade rat mesothelioma. Reviewed

    Hu Q, Akatsuka S, Yamashita Y, Ohara H, Nagai H, Okazaki Y, Takahashi T, Toyokuni S.

    Lab Invest   Vol. 90 ( 3 ) page: 360-373   2010.3

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  39. *A quantitative trait locus responsible for inducing B‐cell lymphoblastic lymphoma is a hotspot for microsatellite instability Reviewed

    Kaszynski RH, Akatsuka S, Hiratsuka T, Jin G, Ozeki M, Okuno T, Nakamura T, Manabe T, Takakuwa T, Hiai H, Toyokuni S, Tamaki K, Tsuruyama T.

    Cancer Sci   Vol. 101 ( 3 ) page: 800-805   2010.3

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  40. Genome-wide analysis identifies a tumor suppressor role for aminoacylase 1 in iron-induced rat renal cell carcinoma. Reviewed

    Zhong Y, Onuki J, Yamasaki T, Ogawa O, Akatsuka S, Toyokuni S.

    Carcinogenesis   Vol. 30 ( 1 ) page: 158-164   2009.1

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  41. Characteristics and modifying factors of asbestos-induced oxidative DNA damage Reviewed

    Jiang L, Nagai H, Ohara H, Hara S, Tachibana M, Hirano S, Shinohara Y, Kohyama N, Akatsuka S, Toyokuni S

    Cancer Sci   Vol. 99 ( 11 ) page: 2142-2151   2008.11

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  42. *Chronic oxidative stress causes amplification and overexpression of ptprz1 protein tyrosine phosphatase to activate beta-catenin pathway Reviewed

    Liu YT, Shang D, Akatsuka S, Ohara H, Dutta KK, Mizushima K, Naito Y, Yoshikawa T, Izumiya M, Abe K, Nakagama H, Noguchi N, Toyokuni S

    Am J Pathol   Vol. 171 ( 6 ) page: 1978-1988   2007.12

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  43. Pathological investigation of oxidative stress in the post-genomic era Reviewed

    Toyokuni S, Akatsuka S.

    Pathol Int   Vol. 57 ( 8 ) page: 461-473   2007.12

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  44. Association of microRNA-34a overexpression with proliferation is cell type-dependent Reviewed

    Dutta KK, Zhong Y, Liu YT, Yamada T, Akatsuka S, Hu Q, Yoshihara M, Ohara H, Takehashi M, Shinohara T, Masutani H, Onuki J, Toyokuni S

    Cancer Sci   Vol. 98 ( 12 ) page: 1845-1852   2007.12

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  45. Novel screening method for ultraviolet protection: combination of a human skin-equivalent model and 8-hydroxy-2'-deoxyguanosine Reviewed

    Toyokuni S, Yasui H, Date A, Hakozaki T, Akatsuka S, Kohda H, Yoshii T, Sakurai H

    Pathol Int   Vol. 56 ( 12 ) page: 760-762   2006.12

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  46. Deletion and single nucleotide substitution at G:C in the kidney of gpt delta transgenic mice after ferric nitrilotriacetate treatment Reviewed

    Jiang L, Zhong Y, Akatsuka S, Liu Y-T, Dutta KK, Lee W-H, Onuki J, Masymura K, Nohmi T, Toyokuni S

    Cancer Sci   Vol. 97 ( 11 ) page: 1159-1167   2006.11

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  47. *Contrasting genome-wide distribution of 8-hydroxyguanine and acrolein-modified adenine during oxidative stress-induced renal carcinogenesis. Reviewed

    Akatsuka S, Aung TT, Dutta KK, Jiang L, Lee W-H, Liu Y-T, Onuki J, Shirase T, Yamasaki K, Ochi H, Naito Y, Yoshikawa T, Kasai H, Tominaga Y, Sakumi K, Nakabeppu Y, Kawai Y, Uchida K, Yamasaki A, Tsuruyama T, Yamada Y, Toyokuni S

    Am J Pathol   Vol. 169 ( 4 ) page: 1328-1342   2006.10

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  48. Alpha-tocopherol induces calnexin in renal tubular cells: another protective mechanism against free radical-induced cellular damage Reviewed

    Lee W-H, Akatsuka S, Shirase T, Dutta KK, Jiang L, Liu Y-T, Onuki J, Yamada Y, Okawa K, Wada Y, Watanabe A, Kohro T, Noguchi N, Toyokuni S

    Arch Biochem Biophys   Vol. 453 ( 2 ) page: 168-178   2006.9

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  49. What has been learned from the studies of oxidative stress-induced carcinogenesis: proposal of the concept of oxygenomics Reviewed

    Toyokuni S, Akatsuka S.

    J Clin Biochem Nutr   Vol. 39 ( 1 ) page: 3-10   2006.7

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  50. Susceptibility of actin to modification by 4-hydroxy-2-nonenal Reviewed

    Ozeki M, Miyagawa-Hayashino A, Akatsuka S, Shirase T, Lee W-H, Uchida K, Toyokuni S

    J Chromatogr B Analyt Technol Biomed Life Sci   Vol. 827 ( 1 ) page: 119-126   2005.11

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  51. Two distinct mechanisms for loss of thioredoxin-binding protein-2 in oxidative stress-induced renal carcinogenesis Reviewed

    Dutta KK, Nishinaka Y, Masutani H, Akatsuka S, Aung TT, Shirase T, Lee W-H, Yamada Y, Hiai H, Yodoi J, Toyokuni S

    Lab Invest   Vol. 85 ( 6 ) page: 798-807   2005.6

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  52. Redox regulation of annexin 2 and its implications for oxidative stress-induced renal carcinogenesis and metastasis Reviewed

    Tanaka T, Akatsuka S, Ozeki M, Shirase T, Hiai H, Toyokuni S

    Oncogene   Vol. 23 ( 22 ) page: 3980-3989   2004.5

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  53. Detection of glyceraldehyde 3-phosphate dehydrogenase messenger RNA using a peptide nucleic acid probe in paraffin-embedded archival specimens Reviewed

    Hiroyasu M, Akatsuka S, Shirase T, Toda Y, Hiai H, Toyokuni S

    Pathol Int   Vol. 54 ( 4 ) page: 251-255   2004.4

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  54. Effects of phenolic contents of Mauritian endemic plant extracts on promoter activities of antioxidant enzymes Reviewed

    Toyokuni S, Tanaka T, Kawaguchi W, Fang NRL, Ozeki M, Akatsuka S, Hiai H, Aruoma OI, Bahorun T

    Free Radic Res   Vol. 37 ( 11 ) page: 1215-1224   2003.11

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  55. Intermittent microwave irradiation facilitates antigen-antibody reaction in Western blot analysis Reviewed

    Toyokuni S, Kawaguchi W, Akatsuka S, Hiroysu M, Hiai H

    Pathol Int   Vol. 53 ( 4 ) page: 259-261   2003.4

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  56. Temperature dependencies of spreading coefficients of hydrocarbons on water Reviewed

    Akatsuka S, Yoshigiwa H, Mori YH

    J Colloid Interf Sci   Vol. 172 ( 2 ) page: 335-340   1995.6

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Books 7

  1. 第5章 第1節 酸化ストレス

    赤塚慎也,豊國伸哉( Role: Joint author)

    エヌ・ティー・エス(生命金属ダイナミクス,207-214頁)  2021.1 

  2. 酸化ストレスによる発がんとゲノム変化

    赤塚慎也、豊國伸哉( Role: Joint author)

    別冊・医学のあゆみ「レドックスUPDATE」 162-167頁  2015.7 

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    Language:Japanese

  3. 発がんと酸化ストレス

    赤塚慎也,豊國伸哉( Role: Joint author)

    診断と治療社 (酸化ストレスの医学 改訂第2版 169-175頁)  2014.9 

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    Language:Japanese

  4. 酸化ストレスによるゲノム変化と発がん

    赤塚慎也,豊國伸哉( Role: Joint author)

    羊土社(実験医学 30巻 17号 2779-2785頁)  2012.11 

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    Language:Japanese

  5. 鉄・酸化ストレスによる発癌の分子機構を探る

    赤塚慎也,豊國伸哉( Role: Joint author)

    先端医学社(分子消化器病 5巻 1号 39-48頁)  2008.3 

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    Language:Japanese

  6. 生体金属と活性酸素・フリーラジカル

    赤塚慎也,豊國伸哉( Role: Joint author)

    アグネ技術センター(金属 77巻 3号 305-310頁)  2007.3 

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    Language:Japanese

  7. オキシゲノミクス-酸化ストレス発癌とゲノム

    赤塚慎也,豊國伸哉( Role: Joint author)

    医歯薬出版株式会社(別冊・医学のあゆみ「酸化ストレス Ver.2」 16-19頁)  2006.10 

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    Language:Japanese

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KAKENHI (Grants-in-Aid for Scientific Research) 4

  1. 発がんにおけるDNA損傷・修復ダイナミクスの実像解明

    Grant number:20K07588  2020.4 - 2023.3

    科学研究費助成事業  基盤研究(C)

    赤塚 慎也, 豊國 伸哉

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    Authorship:Principal investigator 

    Grant amount:\4290000 ( Direct Cost: \3300000 、 Indirect Cost:\990000 )

    本研究は、DNA損傷のゲノム内分布動態を確定するための方法として次世代シークエンサーを用いた新たな解析法を確立し、発がん刺激によるDNA損傷分布の変化とその意義を明らかにすることを目的とする。DNA損傷は遺伝子変異の原因となるため、そのゲノム内での分布動態を知ることは、がんの発生経路を確定し、予防の方策を講ずるうえで重要となる。本研究では、損傷DNAに対する免疫沈降産物の網羅的解析を次世代シークエンサーの新たな応用技術として確立し、発がん過程におけるDNA損傷のゲノム分布動態を解明する。さらに、その際の変異の発生頻度を評価することにより、DNA損傷分布変化の発がんにおける意義を明らかにする。
    酸化ストレス等によるゲノムDNAの損傷は、発がんの原因になると考えられている。したがって、がんの発生経路を詳細に解析するためには、発がんの過程にある細胞のゲノム内におけるDNA損傷の分布動態を知ることが重要となる。近年、DNAのメチル化やヒストン修飾などのエピゲノム情報のプロファイリングについては、次世代シークエンサーを用いた方法によりハイスループット化、高解像度化が図られている。しかしながら、ゲノム部位間での損傷頻度の違いを網羅的に評価するための技術は未だ十分に確立されていない。本研究では、損傷DNAに対する免疫沈降産物の網羅的解析を次世代シークエンサーの新たなアプリケーションとして確立し、発がん過程におけるDNA損傷のゲノム分布動態を解明する。さらに、その際の変異の発生頻度を評価することにより、DNA損傷分布変化の発がんにおける意義を明らかにする。
    本研究課題では、鉄ニトリロ三酢酸誘発げっ歯類発がんモデルを用い、その標的臓器となる腎臓の組織細胞より抽出したゲノムDNAについて抗8-オキソグアニン抗体を用いて免疫沈降を実施し、酸化的DNA損傷のゲノム内分布解析を行う。
    正常時および鉄ニトリロ三酢酸腹腔内投与後3時間(酸化ストレス亢進時)のマウス腎組織を採取し、ゲノムDNAを抽出した。8-オキソグアニンに対する抗体を使用してDNA免疫沈降を施行した。次世代シークエンサーによる分布解析を実施する前に、得られた免疫沈降産物を、リアルタイムPCRを用いて評価した。リアルタイムPCRによる結果を以前のアレイCGHによる結果と比較し、それぞれの方法でのバイアスの評価を行った。
    全体として、当年度の新型コロナ感染症流行への対応により、教育その他の業務量が増えてしまい、研究に割ける時間が当初より少なくなってしまったため、多少なりとも課題の推進に影響した。次年度以降はその他業務の効率化とともに時間配分を抑えることにより、進捗状況を回復する予定。
    また、研究内容に関連しては、関連研究の新しい報告に対応して実験原理の再評価と見直しを行ったため、次世代シークエンサー解析の前にその工程に当てる時間が必要となった。しかし、実験結果の品質向上のために価値のある工程であった。
    実験原理の再評価の成果を踏まえて、次世代シークエンサーによる解析方法を確立する。これまでのCGH用マイクロアレイを用いた解析の結果と比較検討しつつ、次世代シークエンサー解析による実験プロトコルおよびデータ解析パイプラインの最適化を行う。次世代シークエンシングのプラットフォームとしては、米国illumina社のHiSeqシステムを採用する。本研究においては、1サンプルあたりのシークエンスリード数は2,000万リードを目途としてシークエンスを実施する。方法について十分な妥当性を得たうえで、着実に当初の計画を遂行し、生物学的・医学的価値の高い結果を収集する。

  2. Analyses based on iron dynamics and multiomics to overcome oxidative stress-induced carcinogenesis

    Grant number:17H04064  2017.4 - 2020.3

    Toyokuni Shinya

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    Authorship:Coinvestigator(s) 

    This project was planned to establish a basis for novel cancer prevention by evaluating iron dynamics multidimensionally. We established the concept of ferroptosis, as catalytic Fe(II)-dependent regulated necrosis, based on our experience of iron-induced carcinogenesis. We used phlebotomy to remove excess iron in crocidolite-induced mesothelial carcinogenesis, which significantly prolonged survival and reduced tumor burden. We used knockout (KO) mice of 3 repair genes for 8-oxoguanine (Ogg1, Mutyh and Mth1) and found that Mutyh KO showed a tendency to increase iron-induced renal carcinogenesis whereas Mth1 KO significantly reduced crocidolite-induced malignant mesothelioma (MM) in females. MM induction by crocidolite was delayed in Dmt1 transgenic mice. We also found that carbonic anhydrase 9 (CA9) confers ferroptosis-resistance to MM cells in hypoxia. Thus, CA9 can be another target for cancer therapy. In conclusion, iron metabolism regulates not only carcinogenesis but tumor biology.

  3. 発がん過程におけるDNA損傷・修復のゲノム内分布動態の解明

    2010 - 2012

    科学研究費補助金  基盤研究(C),課題番号:22500997

    赤塚慎也

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    Authorship:Principal investigator 

  4. 酸化ストレス誘発動物発癌モデルにおける染色体変化の解析

    2007 - 2008

    科学研究費補助金  基盤研究(C),課題番号:19500361

    赤塚 慎也

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    Authorship:Principal investigator 

 

Teaching Experience (On-campus) 2

  1. 基礎医学セミナー

    2017

  2. 基礎セミナー

    2017