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E-brochureMolecular Pathology

Master's Program Human Sciences, Graduate School of Medicine
Doctor's Program Medical Science Division, Department of Medical Science, Graduate School of Medicine, Science and Technology

Staff List

Senior Assistant Professor KAWAKUBO Masatomo

Summary of Activity

Glycans are regarded as the third biological chains of fundamental biopolymers, followed by nucleic acids and proteins, that closely associated with the biological phenomena such as development, immunity, infection, and cancer. We investigate the participation of glycans in causes of various diseases using techniques such as morphology, molecular biology, biochemistry and genetic engineering. Recently, we demonstrated that αGlcNAc protects gastric mucosa against Helicobacter pylori (H. pylori) infection and serves as a tumor suppressor for differentiated-type gastric adenocarcinoma.

Research Subject

  • ・Functional analysis of glycans using genetically engineered mice.
  • ・Role of gastric gland mucin-specific O-glycans in preventing gastric cancer.
  • ・Investigation of various helicobacter species in gastric diseases.

Outlook for Research

It may be useful for novel molecular therapies and diagnoses of cancer and inflammation through elucidation of the biological functions of glycans expressed on cell surface or secreted from cells under pathological conditions. In addition, anti-microbial drug design exhibiting an anti-microbial effect on H. pylori can be provided. H. pylori resistant to antibiotics become the problem of eradication currently.

Major Publications

1. Kobayashi J, Kawakubo M, Fujii C, Arisaka N, Miyashita M, Sato Y, Komura H, Matoba H, Nakayama J: Cholestenone functions as an antibiotic against Helicobacter pylori by inhibiting biosynthesis of the cell wall component CGL. Proc Natl Acad Sci USA 118, e2016469118, 2021.

2. Matoba H, Takamoto M, Fujii C, Kawakubo M, Kasuga E, Matsumura T, Natori T, Misawa K, Taniguchi S, Nakayama J: Cecal tumorigenesis in aryl hydrocarbon receptor-deficient mice depends on cecum-specific mitogen-activated protein kinase pathway activation and inflammation. Am J Pathol 190, 453-468, 2020.

3. Kawakubo M, Komura H, Goso Y, Okumura M, Sato Y, Fujii C, Miyashita M, Arisaka N, Harumiya S, Yamanoi K, Yamada S, Kakuta S, Kawashima H, Fukuda MN, Fukuda M, Nakayama J: Analysis of A4gnt knockout mice reveals an essential role for gastric sulfomucins in preventing gastritis cystica profunda. J Histochem Cytochem 67, 759-770, 2019.

4. Ohya A, Yamanoi K, Shimojo H, Fujii C, Nakayama J: Gastric gland mucin-specific O-glycan expression decreases with tumor progression from precursor lesions to pancreatic cancer. Cancer Sci 108, 1897-1902, 2017.

5. Kawakubo M, Horiuchi K, Komura H, Sato Y, Kato M, Ikeyama M, Fukushima M, Yamada S, Ishizone S, Matsumoto T, Ota H, Sagara J, Nakayama J: Cloning of Helicobacter suis cholesterol -glucosyltransferase and production of an antibody capable of detecting it in formalin-fixed, paraffin-embedded gastric tissue sections. Histochem Cell Biol 148, 463-471, 2017.

6. Yamanoi K, Sekine S, Higuchi K, Kushima R, Nakayama J: Decreased expression of gastric gland mucin-specific glycan 1,4-linked N-acetylglucosamine on its scaffold mucin 6 is associated with malignant potential of pyloric gland adenoma of the stomach. Histopathology 67, 898-904, 2015.

7. Yamada S, Okamura T, Kobayashi S, Tanaka E, Nakayama J: Reduced gland mucin-specific O-glycan in gastric atrophy: A possible risk factor for differentiated-type adenocarcinoma of the stomach. J Gastroenterol Hepatol 30, 1478-1484, 2015.

8. Shiratsu K, Higuchi K, Nakayama J: Loss of gastric gland mucin-specific O-glycan is significantly associated with progression of differentiated-type adenocarcinoma of the stomach. Cancer Sci 105, 126-133, 2014.

9. Karasawa F, Shiota A, Goso Y, Kobayashi M, Sato Y, Masumoto J, Fujiwara M, Yokosawa S, Muraki T, Miyagawa S, Ueda M, Fukuda MN, Fukuda M, Ishihara K, Nakayama J: Essential role of gastric gland mucin in preventing gastric cancer in mice. J Clin Invest 122, 923-934, 2012.

10. Kawakubo M, Ito Y, Okimura Y, Kobayashi M, Sakura K, Kasama S, Fukuda MN, Fukuda M, Katsuyama T, Nakayama J: Natural antibiotic function of a human gastric mucin against Helicobacter pylori infection. Science 305, 1003-1006, 2004.

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