TOP PAGE

Hiroto Kawashima

Research Interest

This laboratory focuses on the functional roles of glycans in lymphocyte homing and immune responses.
Lymphocyte homing is mediated by a specific interaction between the lymphocyte homing receptor L-selectin and its sulfated glycoprotein ligands expressed on high endothelial venules in the lymph nodes. We previously found that the sulfation of L-selectin ligands plays a major role in lymphocyte homing using gene-targeted mice deficient in two sulfotransferases, GlcNAc6ST-1 and GlcNAc6ST-2. We are currently investigating the roles of glycans in allergy and immune-related diseases using gene-targeted mice.  

CV

Name: Hiroto Kawashima, Ph.D.
Position title: Professor
Office Address: Laboratory of Microbiology and Immunology, 
Graduate School of Pharmaceutical Sciences, Chiba Univerisity 
1-8-1 Inohana, Chuo-ku, Chiba 260-0856, Japan
Phone: +81-43-226-2926
FAX: +81-43-226-2927
E-mail: h-kawashima@chiba-u.jp

EDUCATIONAL HISTORY
1988 B.S., Faculty of Pharmaceutical Sciences, The University of Tokyo
1990 M.S., Graduate School of Pharmaceutical Sciences, The University of Tokyo
1993 Ph.D., Graduate School of Pharmaceutical Sciences, The University of Tokyo

PROFESSIONAL EXPERIENCE
1993-1994: Research fellow, Department of Immunology, Tokyo Metropolitan Institute of Medical Science
1994-2001: Assistant Professor, Department of Bioregulation, Osaka University Graduate School of Medicine
2001-2005: Postdoctoral research associate, The Burnham Institute, La Jolla, CA
2005-2014: Associate Professor, School of Pharmaceutical Sciences, University of Shizuoka
2014-2015: Professor, School of Pharmacy and Pharmaceutical Sciences, Hoshi University
2015-present: Professor, Graduate School of Pharmaceutical Sciences, Chiba University

MEMBERSHIPS
American Society for Biochemistry and Molecular Biology (ASBMB)
Federation of American Societies for Experimental Biology (FASEB)
American Association of Immunologists (AAI)
Society for Glycobiology
The Pharmaceutical Society of Japan
The Japanese Society for Immunology
The Japanese Biochemical Society
The Japanese Cancer Association

AWARDS AND HONORS
2001 The Japanese Society of Inflammation and Regeneration Young Investigator Award

MAJOR RESEARCH INTERESTS
1. Molecular mechanisms underlying lymphocyte homing.
2. Roles of complex carbohydrates in immunity.

SELECTED PUBLICATIONS
【Original Papers】
Ohishi K, Ishikura A, Nishida S, Abo H, Nakatsukasa H, and Kawashima H. Sialyl Lewis X defines an activated and functional regulatory T cell subpopulation in mice.
J. Immunol., 212:1627-1638, 2024.
 
Liu Q, Xiong W, Obara S, Abo H, Nakatsukasa H, and Kawashima H. Prevention of experimental autoimmune encephalomyelitis by targeting 6-sulfo sialyl Lewis X glycans involved in lymphocyte homing.
Int. Immunol., 36:303-316, 2024.
  
Liu W, Xiong W, Liu W, Hirakawa J, Kawashima H. A novel monoclonal antibody against 6-sulfo sialyl Lewis x glycans attenuates murine allergic rhinitis by suppressing Th2 immune responses.
Sci. Rep., 13:15740, 2023. 
 
Abo H, Muraki A, Harusato A, Imura T, Suzuki M, Takahashi K, Denning TL, Kawashima H. N-acetylglucosamine-6-O-sulfation on intestinal mucins prevents obesity and intestinal inflammation by regulating gut microbiota.
JCI Insight, e165944, 2023.
 
Sultana MF, Suzuki M, Yamasaki F, Kubota W, Takahashi K, Abo H and Kawashima H. Identification of crucial amino acid residues for antimicrobial activity of angiogenin 4 and its modulation of gut microbiota in mice.
Front. Microbiol., 13:900948, 2022.
 
Tsuboi K, Nishitani M, Takakura A, Imai Y, Komatsu M and Kawashima H. Autophagy protects against colitis by the maintenance of normal gut microflora and secretion of mucus.
J.Biol.Chem., 290:20511-20526, 2015.

Matsumura R, Hirakawa J, Sato K, Ikeda T, Nagai M, Fukuda M, Imai Y and Kawashima H. Novel antibodies reactive with sialyl Lewis X in both humans and mice define its critical role in leukocyte trafficking and contact hypersensitivity responses.
J.Biol.Chem., 290:15313-15326, 2015.

Tsuboi K., Hirakawa J., Seki E., Imai Y., Yamaguchi Y., Fukuda M., and Kawashima H. Role of high　endothelial venule-expressed heparan sulfate in chemokine presentation and lymphocyte homing.
J.Immunol., 191:448-455, 2013.

Ohmichi Y., Hirakawa J., Imai Y., Fukuda M., and Kawashima H. Essential role of peripheral node addressin in lymphocyte homing to nasal-associated lymphoid tissues and allergic immune responses.
J.Exp.Med., 208:1015-1025, 2011.

Hirakawa J., Tsuboi K., Sato K., Kobayashi M., Watanabe S., Takakura A., Imai Y., Ito Y., Fukuda M., and Kawashima H. Novel anti-carbohydrate antibodies reveal the cooperative function of sulfated N- and O-glycans in lymphocyte homing.
J.Biol.Chem., 285:40864-40878, 2010.

Tobisawa Y., Imai Y., Fukuda M., and Kawashima H. Sulfation of colonic mucins by N-acetylglucosamine-6-O-sulfotransferase-2 and its protective function in experimental colitis in mice.
J.Biol.Chem., 285:6750-6760, 2010.

Kawashima H., Hirakawa J., Tobisawa Y., Fukuda M., and Saga Y.. Conditional gene targeting in mouse high endothelial venules.
J.Immunol., 182:5461-5468, 2009.

Mitoma J., Bao X., Petryanik B., Schaerli P., Gauguet J.M., Yu S.Y., Kawashima H., Saito H., Ohtsubo K., Marth J.D., Khoo K.H., von Andrian U.H., Lowe J.B., and Fukuda M. Critical functions of N-glycans in L-selectin-mediated lymphocyte homing and recruitment.
Nature Immunology, 8:409-418, 2007.

Kawashima H., Petryniak B., Hiraoka N., Mitoma J., Huckaby V., Nakayama J., Uchimura K., Kadomatsu K., Muramatsu T., Lowe J.B., and Fukuda M. N-Acetylglucosamine-6-O-sulfotransferases 1 and 2 cooperatively control lymphocyte homing through L-selectin ligand biosynthesis in high endothelial venules.
Nature Immunology, 6:1096-1104, 2005.

Kawashima H., Watanabe N., Hirose M., Sun X., Atarashi K., Kimura T., Shikata K., Matsuda M., Ogawa D., Heljasvaara R., Rehn M., Pihlajaniemi T., and Miyasaka M. Collagen XVIII, a basement membrane heparan sulfate proteoglycan, interacts with L-selectin and monocyte chemoattractant protein-1.
J.Biol.Chem., 278:13069-13076, 2003.

Kawashima H., Atarashi K., Hirose M., Hirose J., Yamada S., Sugahara K., and Miyasaka M. Oversulfated chondroitin/dermatan sulfates containing GlcAβ1/IdoAα1-3GalNAc(4,6-O-disulfate) interact with L- and P-selectin and chemokines.
J.Biol.Chem., 277:12921-12930, 2002.

Kawashima H., Hirose M., Hirose J., Nagakubo D., Plaas H.K.A., and Miyasaka M. Binding of a large chondroitin sulfate/dermatan sulfate proteoglycan, versican, to L-selectin, P-selectin, and CD44.
J.Biol.Chem., 275:35448-35456, 2000.

【Book Chapters】
Kawashima H. Analysis of L-selectin-mediated cellular interactions under flow conditions.
Methods in Molecular Biology, Lectins (Hirabayashi J, ed.), Humana Press. 1200:401-412, 2014.

Kawashima H. Generation of anti-sulfated glycan antibodies using sulfotransferase-deficient mice.
Methods in Molecular Biology, 1022:51-60, 2013.

Kawashima H. Roles of GlcNAc-6-O-sulfotransferases in lymphoid and nonlymphoid tissues.
Methods in Enzymology, 479:243-256, 2010.

Kawashima H. Determination of chemokine-glycosaminoglycan interaction specificity.
Methods in Enzymology, 416:254-263, 2006.

Kawashima H. Functions of glycans revealed by gene inactivation of L-selectin ligand sulfotransferases in mice.
Methods in Enzymology, 416:279-290, 2006.