Juntendo University, Tokyo, established in 1838.

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  4. Mitsuaki Yanagida PhD.

Institute for Environmental and Gender-Specific Medicine

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Mitsuaki Yanagida PhD.

Associate Professor, Institute for Environmental and Gender-Specific Medicine, Juntendo University Graduate School of Medicine

Research Speciality:

We apply proteomic strategies to investigate various biological phenomena and pathology of diseases affected by environmental factors and gender disparity.


Chihiro Kobayashi, M.S. Research Assistant

Research Description:

Proteomics is a powerful tool to explore and understand the molecular mechanisms of biological pathways and pathogenesis of diseases. We use this technology to elucidate various phenomena described below.

(1) Elucidation of pathogenesis of the diseases by proteomic analysis of clinical samples.
One of the research interests that we focus on is collagen diseases such as rheumatoid arthritis (RA), which show higher prevalence in women. The causes of collagen diseases are complex and affected by various host and environmental factors. For exploring the disease-related factors and understanding the mechanisms of pathogenesis of these multifactorial diseases, large scale analyses such as proteomic approaches are of high relevance. We analyze plasma/serum proteome changes in RA patients undergoing biological drug treatment and identify factors related to the pathology of RA in order to develop novel therapeutic strategies.

(2) Peptidomic analysis of clinical samples.
There are various kinds of native peptides in the human biofluids and the patterns of them reflect the state of the body. We focus on the native peptides in the serum of patients with hypertensive disorder of pregnancy (HDP) and examine the relationship between the profiles of these peptides and pathology of HDP.

(3) Functional proteomics by use of protein-protein interaction analysis.
Protein-protein interaction analysis is generally applied to clarify the function of targeted proteins. We explore the cellular roles of many proteins with unknown functions by identifying the protein components of the protein complexes copurified with the targeted proteins. Collaborations are in progress with internal and external research groups of our institute.

Publications (2006-2017)

  1. Hamamura K, Yanagida M, Ishikawa H, Banzai M, Yoshitake H, Nonaka D, Tanaka K, Sakuraba M, Miyakuni Y, Takamori K, Nojima M, Yoshida K, Fujiwara H, Takeda S, Araki Y: Quantitative measurement of a candidate serum biomarker peptide derived from α2-HS-glycoprotein, and a preliminary trial of multidimensional peptide analysis in females with pregnancy-induced hypertension. Ann Clin Biochem, 2017 Jan 1:4563217717748. doi: 10.1177/0004563217717748. [Epub ahead of print]
  2. Yoshitake H, Oda R, Yanagida M, Kawasaki Y, Sakuraba M, Takamori K, Hasegawa A, Fujiwara H, Araki Y: Identification of an anti-sperm auto-monoclonal antibody (Ts4)-recognized molecule in the mouse sperm acrosomal region and its inhibitory effect on fertilization in vitro. J Reprod Immunol, 2016;115: 6-13
  3. Misaki K, Takamura-Enya T, Ogawa H, Takamori K, Yanagida M: Tumour-promoting activity of polycyclic aromatic hydrocarbons and their oxygenated or nitrated derivatives. Mutagenesis, 2016; 31: 205-213.
  4. Hamamura K, Nonaka D, Ishikawa H, Banzai M, Yanagida M, Nojima M, Yoshida K, Lee LJ, Tanaka K, Takamori K, Takeda S, Araki Y: Simple quantitation for potential serum disease biomarker peptides, primarily identified by a peptidomics approach in the serum with hypertensive disorders of pregnancy. Ann Clin Biochem, 2016; 53: 85-96
  5. Iwabuchi K, Masuda H, Kaga N, Nakayama H, Matsumoto R, Iwahara C, Yoshizaki F, Tamaki Y, Kobayashi T, Hayakawa T, Ishii K, Yanagida M, Ogawa H, Takamori K: Properties and functions of lactosylceramide from mouse neutrophils. Glycobiology, 2015; 25: 655-668.
  6. Suzuki S, Morimoto S, Fujishiro M, Kawasaki M, Hayakawa K, Miyashita T, Ikeda K, Miyazawa K, Yanagida M, Takamori K, Ogawa H, Sekigawa I, Takasaki Y: Inhibition of the insulin-like growth factor system is a potential therapy for rheumatoid arthritis. Autoimmunity, 2015; 48: 251-258.
  7. Yanagida M, Kawasaki M, Fujishiro M, Miura M, Ikeda K, Nozawa K, Kaneko H, Morimoto S, Takasaki Y, Ogawa H, Takamori K, Sekigawa I: Serum proteome analysis in patients with rheumatoid arthritis receiving therapy with tocilizumab, an anti-interleukin-6 receptor antibody. Biomed Res Int, 2013; 2013: 607137.
  8. Nozawa K, Fujishiro M, Kawasaki M, Yamaguchi A, Ikeda K, Morimoto S, Iwabuchi K, Yanagida M, Ichinose S, Morioka M, Ogawa H, Takamori K, Takasaki Y, Sekigawa I: Inhibition of connective tissue growth factor ameliorates rheumatoid arthritis in a murine model. Arthritis Rheum, 2013; 65: 1477-1486.
  9. Fu L, Kitamura T, Iwabuchi K, Ichinose S, Yanagida M, Ogawa H, Watanabe S, Maruyama T, Suyama M, Takamori K: Interplay of neuropilin-1 and semaphorin 3A after partial hepatectomy in rats. World J Gastroenterol, 2012; 18: 5034-5041.
  10. Yanagida M, Jung G, Tanaka Y, Sone S, Fujishiro M, Ikeda K, Nozawa K, Kaneko H, Takasaki Y, Ogawa H, Takamori K, Sekigawa I: Serum proteome analysis in patients with rheumatoid arthritis receiving therapy with etanercept, a chimeric tumor necrosis factor-alpha receptor. Int J Rheumatic Dis, 2012; 15: 486-495.
  11. Okada M, Hozumi Y, Tanaka T, Suzuki Y, Yanagida M, Araki Y, Evangelisti C, Yagisawa H, Topham MK, Martelli AM, Goto K: DGKζ is degraded through the cytoplasmic ubiquitin-proteasome system under excitotoxic conditions, which causes neuronal apoptosis because of aberrant cell cycle reentry. Cell Signal, 2012; 24: 1573-1582.
  12. Okada M, Hozumi Y, Iwazaki K, Misaki K, Yanagida M, Araki Y, Watanabe T, Yagisawa H, Topham MK, Kaibuchi K, Goto K: DGKζ is involved in LPS-activated phagocytosis through IQGAP1/Rac1 pathway. Biochem Biophys Res Commun, 2012; 420: 479-484.
  13. Fujishiro M, Nozawa K, Kawasaki M, Yamaguchi A, Iwabuchi K, Yanagida M, Suzuki F, Miyazawa K, Fukui H, Kaneko K, Ogawa H, Takamori K, Takasaki Y, Sekigawa I: Regenerating gene (REG) 1 alpha promotes pannus progression in patients with rheumatoid arthritis. Mod Rheumatol, 2012; 22: 228-237.
  14. Araki Y, Nonaka D, Tajima A, Maruyama M, Nitto T, Ishikawa H, Yoshitake H, Yoshida E, Kuronaka N, Asada K, Yanagida M, Nojima M, Yoshida K, Takamori K, Hashiguchi T, Maruyama I, Lee L, Tanaka K: Quantitative peptidomic analysis by a newly developed one-step direct transfer technology without depletion of major blood proteins: Its potential utility for monitoring of pathophysiological status in pregnancy-induced hypertension. Proteomics, 2011; 11: 2727-2737.
  15. Yoshitake H, Yanagida M, Maruyama M, Takamori K, Hasegawa A, Araki Y: Molecular characterization and expression of dipeptidase 3, a testis-specific membrane-bound dipeptidase: complex formation with TEX101, a germ-cell-specific antigen in the mouse testis. J Reprod Immunol, 2011; 90: 202-213.
  16. Nozawa K, Fujishiro M, Kawasaki M, Kaneko H, Iwabuchi K, Yanagida M, Suzuki F, Miyazawa K, Takasaki Y, Ogawa H, Takamori K, Sekigawa I: Connective tissue growth factor promotes articular damage by increased osteoclastogenesis in patients with rheumatoid arthritis. Arthritis Res Ther, 2009;11:R174.
  17. Yamatoya K, Yoshida K, Ito C, Maekawa M, Yanagida M, Takamori K, Ogawa H, Araki Y, Miyado K, Toyama Y, Toshimori K: Equatorin: Identification and characterization of the epitope of the MN9 antibody in the mouse. Biol Reprod, 2009; 81: 889-897.
  18. Fujiyama-Nakamura S, Yoshikawa H, Homma K, Hayano T, Tsujimura-Takahashi T, Izumikawa K, Ishikawa H, Miyazawa N, Yanagida M, Miura Y, Shinkawa T, Yamauchi Y, Isobe T, Takahashi N: Parvulin (Par14), a peptidyl prolyl cis-trans isomerase, is a novel rRNA-processing factor evolved in the metazoan lineage. Mol Cell Proteomics, 2009; 8: 1552-1565.
  19. Izumikawa K, Yanagida M, Hayano T, Tachikawa H, Komatsu W, Shimamoto A, Futami K, Furuichi Y, Shinkawa T, Yamauchi Y, Isobe T, Takahashi N: Association of human DNA helicase RecQ5b with RNA polymerase II and its possible role in transcription. Biochem J, 2008; 413: 505-516.
  20. Sekigawa I*, Yanagida M*, Iwabuchi K, Kaneda K, Kaneko H, Takasaki Y, Jung G, Sone S, Tanaka Y, Ogawa H, Takamori K: Protein biomarker analysis by mass spectrometry in patients with rheumatoid arthritis receiving anti-tumor necrosis factor- antibody therapy. Clin Exp Rheumatol, 2008; 26: 261-267. *: equal contribution
  21. Hayashi C*, Ono Y*, Doi N, Kitamura F, Tagami M, Mineki R, Arai T, Taguchi H, Yanagida M, Hirner S, Labeit D, Labeit S, Sorimachi H: Multiple molecular interactions implicate Connectin/Titin N2A region as a modulating scaffold for p94/Calpain 3 activity in skeletal muscle. J Biol Chem, 2008; 283: 14801-14814. *: equal contribution
  22. Morigasaki S, Shimada K, Ikner A, Yanagida M, Shiozaki K: Glycolytic enzyme GAPDH promotes peroxide stress signaling through multistep phosphorelay to a MAPK cascade. Mol Cell, 2008; 30: 108-113.
  23. Yanagida M, Iwabuchi K: Proteomic analysis of lactosylceramide-enriched membrane microdomains. Trends Glycosci Glycotech, 2008; 20: 1-15.
  24. Ono Y, Hayashi C, Doi N, Kitamura F, Shindo M, Kudo K, Tsubata T, Yanagida M, Sorimachi H: Comprehensive survey of p94/calpain 3 substrates by comparative proteomics - Possible regulation of protein synthesis by p94. Biotechnol J, 2007; 2: 565-576.
  25. Yanagida M, Nakayama H, Yoshizaki F, Fujimura T, Takamori K, Ogawa K, Iwabuchi K: Proteomic analysis of plasma-membrane lipid rafts of HL-60 cells. Proteomics, 2007; 7: 2398-2409.
  26. Tsukamoto H, Yoshitake H, Mori M, Yanagida M, Takamori K, Ogawa H, Takizawa T, Araki Y: Testicular proteins associated with the germ cell-marker, TEX101: Involvement of cellubrevin in TEX101-trafficking to the cell surface during spermatogenesis. Biochem Biophys Res Commun, 2006; 345: 229-238.
  27. Sekiguchi T, Hayano T, Yanagida M, Takahashi N, Nishimoto T: NOP132 is required for proper nucleolus localization of DEAD-box RNA helicase DDX47. Nucleic Acids Res, 2006; 34: 4593-4608.
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