News & Topics
- April 1, 2023
- October 20, 2022
- June 14, 2022
Two undergraduate students (Faculty of Radiological Technology) joined our group.
Prof. Roger A. Laine (Louisiana State University) is staying at our lab during his savatical leave.
Six undergraduate students (Faculty of Medical Technology) joined our group.
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.
・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
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.
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
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
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
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.
Research progress meeting & Journal club
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.
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.
- Suganuma Y, Imamura A, Ando H, Kiso M, Takematsu H, Tsubata T, Ishida H. Improved synthesis of CD22-binding sialosides and its application for further development of potent CD22 inhibitors. Glycoconj J. 2023 Apr;40(2):225-246.
- Takada M, Fukuhara D, Takiura T, Nishibori Y, Kotani M, Kiuchi Z, Kudo A, Beltcheva O, Ito-Nitta N, Nitta KR, Kimura T, Suehiro JI, Katada T, Takematsu H, Yan K. Involvement of GLCCI1 in mouse spermatogenesis. FASEB J. 2023 Jan;37(1):e22680.
- Hada I, Shimizu A, Takematsu H, Nishibori Y, Kimura T, Fukutomi T, Kudo A, Ito-Nitta N, Kiuchi Z, Patrakka J, Mikami N, Leclerc S, Akimoto Y, Hirayama Y, Mori S, Takano T, Yan K. A Novel Mouse Model of Idiopathic Nephrotic Syndrome Induced by Immunization with the Podocyte Protein Crb2. J Am Soc Nephrol. 2022 Nov;33(11):2008-2025.
- Doi H, Matsui T, Dijkstra JM, Ogasawara A, Higashimoto Y, Imamura S, Ohye T, Takematsu H, Katsuda I, Akiyama H. Andrographolide, isolated from Andrographis paniculata, induces apoptosis in monocytic leukemia and multiple myeloma cells via augmentation of reactive oxygen species production. F1000Res. 2021 Jul 6;10:542.
- Takahashi S, Fukuhara D, Kimura T, Fukutomi T, Tanaka E, Mikami N, Hada I, Takematsu H, Nishibori Y, Akimoto Y, Kiyonari H, Abe T, Huber O, Yan K. USP40 deubiquitinates HINT1 and stabilizes p53 in podocyte damage. Biochem Biophys Res Commun. 2022 Jul 23;614:198-206.
- Enterina JR, Sarkar S, Streith L, Jung J, Arlian BM, Meyer SJ, Takematsu H, Xiao C, Baldwin TA, Nitschke L, Shlomchick MJ, Paulson JC, Macauley MS. Coordinated changes in glycosylation regulate the germinal center through CD22. Cell Rep. 2022 Mar 15;38(11):110512.
- Akatsu C, Alborzian Deh Sheikh A, Matsubara N, Takematsu H, Schweizer A, Abdu-Allah HHM, Tedder TF, Nitschke L, Ishida H, Tsubata T. Chondroitin 6-sulphate is required for neuroplasticity and memory in ageing. Sci Signal. 2022 Mar;15(723):eabf9570.
- 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.
- Taishi Yuasa, Yuko Naito-Matsui, Hiromu Takematsu. スフィンゴ糖脂質CD77の発現によるCD19上のN型糖鎖の変化はB細胞抗原受容体シグナル伝達の抑制に関わる. 糖鎖科学中部拠点 18th “Wakate-no-chikara” forum (January, oral)
- Taishi Yuasa, 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糖脂質CD77はシグナル伝達分子CD19を制御する. The 95th Annual Meeting of the japanese Biochemical Society (November, oral and poster)
- Yuko Naito-Matsui, Hikari Asano, Kumiko Hamano-Takada, Takeshi Tsubata, Shogo Oka, Hiromu Takematsu. Modulation of B cell receptor signaling in germinal center B cells by PNA epitope. Sialoglyco2022 (September, oral)
- 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)
- Yuko Naito-Matsui. Sialoglycan-modified mice to evaluate evolutional effects. SEIKAGAKU. 2020; 92(2):263-267. (Japanese)
- Access to Fujita Health University ⇒ Fujita Health University Homepage
- Access to Molecular Cell Biology ⇒ Room 332, University Building 3