Department of Molecular Cell Biology, Research Promotion Unit,
School of Medical Sciences, Fujita Health University

News & Topics

  • April 1, 2022
  • One undergraduate student (Faculty of Radiological Technology) has joined our group.

  • June 14, 2021
  • Seven undergraduate students (Faculty of Medical Technology) have joined our group.

  • April 1, 2021
  • Two undergraduate students (Faculty of Radiological Technology) have joined our group.

  • April 1, 2021
  • Dr. Nurşah Ertunç has joined our group.

Introduction

We offer laboratory research opportunities of senior thesis to undergraduate/graduate students of School of Medical Sciences/Graduate School of Health Science, both in Faculties of Medical Technology and Radiological Technology. Research will be performed using a variety of principles in biochemistry, molecular biology, cell biology, immunology etc. Our goal in education is to develop human resources who can actively work in various research fields; not limited to hospital laboratory engineers or radiological technologists. Graduate students will be trained not only to design and conduct research but also to present/discuss their research as independent researchers.

Members

Faculty members

Medical Technology

Radiological Technology

Research Student

Taishi Yuasa

Graduate student

Motoki Igakura, Daichi Sato

Undergraduate course

Mika Kimpara

Research Theme

・Molecular functions of glycan-mediated cellular regulation

The cell surface is covered with glycans. Glycan structures are diverse depending on cell type, cellular differentiation, activation etc.; thus, glycans are often called as “the face of cells”. Glycans show various physiological functions by interacting with glycan-binding molecules (lectins) that recognize specific glycan structures.

1. Biological functions of sialic acids

Sialoglycans

The non-reducing terminus of cell surface glycans are often occupied with sialic acids, nine-carbon acidic sugars that have negative charge. Sialic acids play pivotal roles in various cellular recognition events because of their location and structural diversity by various modification. We are studying functional significance of sialic acid-mediated molecular recognition especially focusing on immune system.

Structure of sialic acids

Sialic acids exhibit very specific expression patterns in mammals. Humans specifically lack the activity of CMP-Neu5Ac hydroxylase that catalyzes the biosynthesis of Neu5Gc, one of the two major sialic acid species in mammals. However, human uptakes Neu5Gc by eating Neu5Gc-containing food, such as red meat. Then, non-self Neu5Gc is expressed on the cell surface as ”xeno- autoantigen”, a uniquely acquired self-antigen. Moreover, Neu5Gc is antigenic in human immune system, that is, human has anti-Neu5Gc antibodies. As a result, Neu5Gc is reported to be a target for chronic autoimmunity. To understand immunological impact of this human-specific reaction to xeno-autoantigen for inflammatory diseases, we are trying to establish human-model mice using Neu5Gc-lacking mice.

2. Physiological significance of germinal center-specific glycan expression

Germinal center

The germinal center is a microenvironment essential in acquired immune response to produce high-affinity antibodies. Neu5Gc is the major sialic acid species in mouse resting lymphocytes. We revealed that Neu5Gc expression is suppressed in B cells after the activation by antigens. This Neu5Gc suppression means the decrease in ligand for CD22 that negatively regulates B cell activation.
GL7 is a monoclonal antibody specifically staining the germinal centers, although its epitope was unknown. We found that GL7 recognizes the activation-dependent Neu5Ac induction (=decrease in Neu5Gc) in mouse lymphocyte (Neu5Gc is also suppressed in activated T cells). In addition to GL7, several antibodies or lectins recognizing specific glycan structures have been used as markers for the germinal centers. We are studying novel glycan functionalities in germinal centers as drastic changes in glycan structure occur in the site for immunological reasons.

・Molecular functions of sphingolipid-mediated signal transduction

Sphingolipids are one of the cellular membrane components. Sphingolipids have diverse molecular species and resultant cellular functionalities. We are trying to understand novel functionalities of sphingolipids to transmit cellular signaling.

1. Novel mechanism to selectively degrade sphingolipid-mediated protein kinase

Ypk1 degradation

ISP-1/myriocin is a new type of immunosuppressant isolated from the entomopathogenic fungus Isalia sinclairii. The structure of ISP-1 resembles to that of sphingosine and ISP-1 was revealed to inhibit the biosynthesis of sphingolipids. We identified YPK1, encoding an AGC family serine/threonine-protein kinase to control protein translation, as one of the components of sphingolipid signaling genes in yeast. This sphingolipid-regulating protein kinase expression is controlled by the nutrient status of cells. Ypk1 is selectively degraded under nitrogen starvation. This seemed to be the case that nutrient-spending Ypk1 is degraded in advance to the bulk protein degradation of autophagy. Ypk1 degradation required specific transportation to vacuoles. We are currently analyzing the molecular mechanism in such intracellular transport system.

2. Molecular mechanism to modulate endomitosis via lyso-glycosphingolipids

Endomitosis

Lyso-sphingolipids are sphingolipids with sphingosine (not conventional ceramide) and hydrophilic head group. Psychosine is a lyso-galactosylceramide, consists of a galactose and a sphingosine. We found that psychosine has an activity to convert otherwise mitotic cells to get into “endomitotic” cell cycle, which skips cytokinesis of M-phase of cell division. Endomitosis is utilized for production of big multiploid cells such as megakaryocytes, precursor cells to platelets. We are currently trying to identify cellular components, which we call “endomitosis module”, required for psychosine-triggered endomitosis, to ultimately understand molecular mechanism of this giant-cell producing cell division.

Annual Events

Research progress meeting & Journal club

Lab Meeting

We have lab meeting once a week. Lab staffs and graduate students present their progress in research project. In journal club, we discuss recently published articles.

Presentation at academic conferences

Lab staffs and graduate students present their research results at domestic and international conferences.

Recreation

We have seasonable events such as welcome party, farewell party, after exam party, year-end party, laboratory trip etc., although these events are currently cancelled because of COVID-19.

Photo Gallery

  • 2020 Graduation Celebration

  • 2021 Graduation ceremony (1)

  • 2021 Graduation ceremony (2)

  • 2022 Graduation ceremony (1)

  • 2022 Graduation ceremony (2)

Academic Activities

Manuscripts

2021

  • Yang S, Gigout S, Molinaro A, Naito-Matsui Y, Hilton S, Foscarin S, Nieuwenhuis B, Tan CL, Verhaagen J, Pizzorusso T, Saksida LM, Bussey TM, Kitagawa H, Kwok JCF, Fawcett JW. Chondroitin 6-sulphate is required for neuroplasticity and memory in ageing. Mol Psychiatry. 2021 Oct;26(10):5658-5668.
  • Alborzian Deh Sheikh A, Akatsu C, Abdu-Allah HHM, Suganuma Y, Imamura A, Ando H, Takematsu H, Ishida H, Tsubata T. The Protein Tyrosine Phosphatase SHP-1 (PTPN6) but Not CD45 (PTPRC) Is Essential for the Ligand-Mediated Regulation of CD22 in BCR-Ligated B Cells. J Immunol. 2021 Jun 1;206(11):2544-2551.
  • Spruit CM, Nemanichvili N, Okamatsu M, Takematsu H, Boons GJ, de Vries RP. N-Glycolylneuraminic Acid in Animal Models for Human Influenza A Virus. Viruses. 2021 May 1;13(5):815.
  • Alborzian Deh Sheikh A, Gomaa S, Li X, Routledge M, Saigoh K, Numoto N, Angata T, Hitomi Y, Takematsu H, Tsuiji M, Ito N, Kusunoki S, Tsubata T. A Guillain-Barré syndrome-associated SIGLEC10 rare variant impairs its recognition of gangliosides. J Autoimmun. 2021 Jan;116:102571.

2020

  • Ertunc N, Sato C, Kitajima K. Sialic acid sulfation is induced by the antibiotic treatment in mammalian cells. Biosci Biotechnol Biochem. 2020 Nov;84(11):2311-2318.
  • Morise J, Yamamoto S, Midorikawa R, Takamiya K, Nonaka M, Takematsu H, Oka S. Distinct Cell Surface Expression Patterns of N-Glycosylation Site Mutants of AMPA-Type Glutamate Receptor under the Homo-Oligomeric Expression Conditions. Int J Mol Sci. 2020 Jul 19;21(14):5101

2019

  • Morise J, Suzuki KGN, Kitagawa A, Wakazono Y, Takamiya K, Tsunoyama TA, Nemoto YL, Takematsu H, Kusumi A, Oka S. AMPA receptors in the synapse turnover by monomer diffusion. Nat Commun. 2019 Nov 20;10(1):5245.
  • Kiuchi Z, Nishibori Y, Kutsuna S, Kotani M, Hada I, Kimura T, Fukutomi T, Fukuhara D, Ito-Nitta N, Kudo A, Takata T, Ishigaki Y, Tomosugi N, Tanaka H, Matsushima S, Ogasawara S, Hirayama Y, Takematsu H, Yan K. GLCCI1 is a novel protector against glucocorticoid-induced apoptosis in T cells. FASEB J. 2019 Jun;33(6):7387-7402.
  • Nakamura A, Morise J, Yabuno-Nakagawa K, Hashimoto Y, Takematsu H, Oka S. Site-specific HNK-1 epitope on alternatively spliced fibronectin type-III repeats in tenascin-C promotes neurite outgrowth of hippocampal neurons through contactin-1. PLoS One. 2019 Jan 10;14(1):e0210193.

Conferences

2021

  • Taishi Yuasa, Kumiko Hamano, Ryosuke Seki, Syogo Oka, Yuko Naito-Matsui, Hiromu Takematsu. ヒト胚中心B細胞マーカーであるスフィンゴ脂質CD77はCD19のN型糖鎖付加を亢進させると共にB細胞抗原受容体シグナル伝達を抑制する. 63rd The Japanese Conference on the Biochemistry of Lipids (June, oral)
  • Taishi Yuasa, Kumiko Hamano, Ryosuke Seki, Syogo Oka, Nurşah Ertunç, Yuko Naito-Matsui, Hiromu Takematsu. ヒト胚中心B細胞マーカーCD77はB細胞抗原受容体シグナル伝達を抑制する. The 85th Annual Meeting of The Japanese Biochemical Society, Chubu Branch (May, oral)
  • Taishi Yuasa, Kumiko Hamano, Ryosuke Seki, Yuko Naito-Matsui, Syogo Oka, Hiromu Takematsu. スフィンゴ糖脂質CD77によるB細胞抗原受容体シグナル伝達の制御機構の解析. 糖鎖科学中部拠点 16th “Wakate-no-chikara” forum (January, oral)

2020

  • Nurşah Ertunç, Chihiro Sato, Ken Kitajima. Induction of sialic acid sulfation by the antibiotic G418 treatment in mammalian cells. The 39th Annual Meeting of The Japanese Society of Carbohydrate Research (November, magazine)

2019

  • Shiori Ueno, Azumi Sato, Syogo Oka, Yuko Naito-Matsui, Hiromu Takematsu. 窒素源飢餓時におけるプロテインキナーゼの選択的オートファジー分解の基質. The 92nd Annual Meeting of The Japanese Biochemical Society (September, oral&poster)
  • Taishi Yuasa, Kumiko Hamano, Ryosuke Seki, Syogo Oka, Yuko Naito-Matsui, Hiromu Takematsu. Analysis of the mechanism controlling B cell receptor signaling by glycosphingolipid CD77. The 38th Annual Meeting of The Japanese Society of Carbohydrate Research (August, oral)
  • Hikari Asano, Kumiko Hamano, Syogo Oka, Yuko Naito-Matsui, Hiromu Takematsu. Development and analysis of model B cells to study regulatory role(s) of PNA-binding glycan in B cell receptor signaling. The 38th Annual Meeting of The Japanese Society of Carbohydrate Research (August, oral)
  • Nurşah Ertunç, Thanyaluck Phitak, Hiroshi Fujita, Chihiro Sato, Ken Kitajima. Occurrence, biosynthesis, and biological significance of sulfated sialic acids in vertebrates. The 38th Annual Meeting of The Japanese Society of Carbohydrate Research (August, oral)
  • Yuko Naito-Matsui. Change in sensitivity to bacterial toxin by lack of N-glycolylneuraminic acid. The 92nd Annual Meeting of Japanese Society for Bacteriology (April, invited)

Review

  • Yuko Naito-Matsui. Sialoglycan-modified mice to evaluate evolutional effects. SEIKAGAKU. 2020; 92(2):263-267. (Japanese)

Access

  • Access to Molecular Cell Biology ⇒ Room101, University Building 10