東北大学大学院医学系研究科・医学部

STAFF

Professor

• Jingu, Keiichi Professor. 神宮 啓一 教授 (兼任)
  

Other Faculty / Staff

• Hashimoto, Takuma

  Lect. 橋本 拓磨 講師

• Hatabi, Khaled

  Assistant Prof. Hatabi, Khaled 助教

CONTACT

OUTLINE

1. Elucidation of the Mechanisms of Radioresistance Induced by Hypoxia and/or Nutrient Deprivation
In cancer tissues, insufficient angiogenesis results in hypoxic regions where cancer cells exhibit radioresistance. Since nutrient availability may also be limited in these regions, our laboratory investigates the molecular mechanisms by which hypoxia and nutrient deprivation induce radioresistance. We have previously reported that the expression and activity of AMP-activated protein kinase (AMPK), a sensor of cellular energy status, and ATM and DNA-PKcs, which play critical roles in the DNA damage response, are increased under hypoxic and/or nutrient-deprived conditions. We are currently investigating the signaling pathways involving these molecules.
2. Elucidation of the Relationship Between Stemness and Radioresistance
The concept of stem cells was originally established in the context of normal tissues, but it is now recognized that cancer stem cells with stem cell-like properties also exist in tumors. In addition, hypoxic and nutrient-deprived microenvironments are thought to influence the maintenance of stemness and radioresistance. Our laboratory investigates (1) the molecular mechanisms by which hypoxia and nutrient deprivation regulate the maintenance of stemness and (2) the relationship between stemness and radioresistance, using mesenchymal stem cells, cancer cells, and induced pluripotent stem cells (iPSCs).

1．低酸素・低栄養による放射線抵抗性誘導の機序解明
癌組織では、不十分な血管新生により低酸素状態にある領域が存在し、そこに位置する癌細胞が放射線抵抗性を示すことが知られています。また、低酸素領域では栄養供給も不足することがあるため、当研究室では低酸素・低栄養環境が放射線抵抗性を誘導する分子機序の解明に取り組んでいます。これまでに、細胞内のエネルギー状態を感知するAMPKや、DNA損傷応答に関与するATMおよびDNA-PKcsの発現・活性が、低酸素や低栄養条件下で亢進することを明らかにしてきました。現在は、これらの分子を介したシグナル伝達経路の解析を進めています。
2．幹細胞性と放射線抵抗性との関係の解明
幹細胞の概念は正常組織において確立されてきましたが、近年では癌組織にも幹細胞の性質をもつ癌幹細胞が存在することが知られています。また、低酸素・低栄養の微小環境は、幹細胞性の維持や放射線抵抗性に影響を及ぼすと考えられています。当研究室では、間葉系幹細胞、癌細胞およびiPS細胞を用いて、(1) 低酸素・低栄養環境が幹細胞性の維持に関与する分子機序、(2) 幹細胞性と放射線抵抗性との関係について、その解明に取り組んでいます。

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  Biosafety Level 2 (BSL-2) Laboratory
  P2レベル実験室

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  Laboratory and Cell Culture Equipment
  実験機器・細胞培養設備

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  X-ray irradiation device
  X線照射装置

ARTICLE

Hashimoto T, et al. Oxamate, an LDHA Inhibitor, Inhibits Stemness Including EMT and High DNA Repair Ability, Induces Senescence, and Exhibits Radiosensitizing Effects in Glioblastoma Cells. Int. J. Mol. Sci., 26(12), 5710, 2025.
URL： https://www.mdpi.com/1422-0067/26/12/5710

Hashimoto T, et al. FDX1 Regulates the Phosphorylation of ATM, DNA-PKcs Akt, and EGFR and Affects Radioresistance Under Severe Hypoxia in the Glioblastoma Cell Line T98G. Int. J. Mol. Sci., 26(7), 3378, 2025.
URL： https://www.mdpi.com/1422-0067/26/7/3378

Urushihara Y, et al. AMPK/FOXO3a Pathway Increases Activity and/or Expression of ATM, DNA-PKcs, Src, EGFR, PDK1, and SOD2 and Induces Radioresistance under Nutrient Starvation. Int. J. Mol. Sci. 24(16), 12828, 2023.
URL： https://www.mdpi.com/1422-0067/24/16/12828

Hashimoto T, et al. AMPK increases expression of ATM through transcriptional factor Sp1 and induces radioresistance under severe hypoxia in glioblastoma cell lines. Biochemical and Biophysical Research Communications 590:82-88, 2022.
URL： https://www.sciencedirect.com/science/article/pii/S0006291X21017174

Shiga S, et al. DNA-PKcs is activated under nutrient starvation and activates Akt, MST1, FoxO3a, and NDR1. Biochemical and Biophysical Research Communications 521(3):668-673, 2020.
URL： https://www.sciencedirect.com/science/article/pii/S0006291X19320352