Research Institute
Department of Molecular Pathogenesis
Member
Director | Koichi Kokame |
---|---|
Laboratory Chief | Masashi Akiyama |
Staff Scientist | Yuka Eura Keiko Maruyama |
Research Assistant | Sheng Ye |
Research
Blood is required to have opposing functions; continuous fluidity and rapid clotting. Altered balance between fluidity and clotting can lead to bleeding or thrombogenesis. In order to overcome cardiovascular diseases related to hemorrhage and thrombosis, we are conducting research on plasma proteins, platelets, vascular endothelial cells with a wide variety of approaches from the molecular to the physiological level. We are also focusing on putting the results of basic research into clinical medicine, such as the development of new diagnostic methods.
Features:
・One of the few laboratories in Japan that studies blood coagulation from the perspective of basic biology
・Genetic analysis of patients with abnormal blood coagulation and functional analysis of genetic abnormalities
・Development of new assay methods that lead to practical use in clinical settings
・Analysis of mice lacking proteins involved in endoplasmic reticulum-associated degradation
Recent Publication
Alpha-HIT assay: A new assay for heparin-induced thrombocytopenia antibody detection using FcγRIIa-coated beads and Alpha technology
Keiko Maruyama, Shigeki Miyata, Koichi Kokame
Res. Pract. Thromb. Haemost. 6, e12818 (2022)
https://doi.org/10.1002/rth2.12818
Siglec-5 and Siglec-14 mediate the endocytosis of ADAMTS13
Masashi Akiyama, Yuka Eura, Koichi Kokame
Thromb. Res. 219, 49-59 (2022)
https://doi.org/10.1016/j.thromres.2022.09.005
Three cases of unprovoked venous thromboembolism with prothrombin p.Arg596Gln variant and literature review of antithrombin resistance
Akihiro Tsuji, Toshiyuki Miyata, Akihiro Sekine, Reiko Neki, Koichi Kokame, Tsutomu Tomita, Yumi Kashima, Ryotaro Asano, Jin Ueda, Tatsuo Aoki, Takeshi Ogo
Intern. Med. (2022)
https://doi.org/10.2169/internalmedicine.9718-22
P2Y12 reaction units and clinical outcomes in acute large artery atherosclerotic stroke: a multicenter prospective study
Kazuki Fukuma, Hiroshi Yamagami, Masafumi Ihara, Tomotaka Tanaka, Toshiyuki Miyata, Shigeki Miyata, Koichi Kokame, Kunihiro Nishimura, Yuriko Nakaoku, Haruko Yamamoto, Mikito Hayakawa, Kenji Kamiyama, Yukiko Enomoto, Ryo Itabashi, Eisuke Furui, Yasuhiro Manabe, Masayuki Ezura, Kenichi Todo, Kazuo Hashikawa, Shinichiro Uchiyama, Kazunori Toyoda, Kazuyuki Nagatsuka
J. Atheroscler. Thromb. 30, 39-55 (2023)
https://doi.org/10.5551/jat.63369
First report of inherited protein S deficiency caused by paternal PROS1 mosaicism
Satomi Nagaya*, Keiko Maruyama*, Atsushi Watanabe, Makiko Meguro-Horike, Yuta Imai, Yuki Hiroshima, Shin-Ichi Horike, Koichi Kokame, Eriko Morishita
Haematologica 107, 330-333 (2022)
https://doi.org/10.3324/haematol.2021.278527
Congenital thrombotic thrombocytopenic purpura: genetics and emerging therapies
Kazuya Sakai, Eriko Hamada, Koichi Kokame, Masanori Matsumoto
Ann. Blood (2022)
https://doi.org/10.21037/aob-22-17
V-ATPase V0a1 promotes Weibel-Palade body biogenesis through the regulation of membrane fission
Yasuo Yamazaki, Yuka Eura, Koichi Kokame
eLife 10, e71526 (2021)
https://doi.org/10.7554/eLife.71526
Commonly used anti-von Willebrand factor antibody for multimer analysis cross-reacts with fibronectin, which is difficult to distinguish from VWF
Yuka Eura, Koichi Kokame
Res. Pract. Thromb. Haemost. 5, e12598 (2021)
https://doi.org/10.1002/rth2.12598
Arf GTPase-Activating proteins SMAP1 and AGFG2 regulate the size of Weibel-Palade bodies and exocytosis of von Willebrand factor
Asano Watanabe, Hikari Hataida, Naoya Inoue, Kosuke Kamon, Keigo Baba, Kuniaki Sasaki, Rika Kimura, Honoka Sasaki, Yuka Eura, Wei-Fen Ni, Yuji Shibasaki, Satoshi Waguri, Koichi Kokame, Yoko Shiba
Biol. Open 10, bio058789 (2021)
https://doi.org/10.1242/bio.058789
A novel homozygous variant of the thrombomodulin gene causes a hereditary bleeding disorder
Makoto Osada*, Keiko Maruyama*, Koichi Kokame, Ryunosuke Denda, Kohei Yamazaki, Hisako Kunieda, Maki Hirao, Seiji Madoiwa, Nobuo Okumura, Mitsuru Murata, Yasuo Ikeda, Kentaro Watanabe, Yuiko Tsukada, Takahide Kikuchi
Blood Adv. 5, 3830-3838 (2021)
https://doi.org/10.1182/bloodadvances.2020003814
Current prophylactic plasma infusion protocols do not adequately reduce long-term microvascular events in Japanese patients with congenital TTP
Kazuya Sakai, Yoshihiro Fujimura, Toshiyuki Miyata, Ayami Isonishi, Koichi Kokame, Masanori Matsumoto
Br. J. Haematol. 194, 444-452 (2021)
https://doi.org/10.1111/bjh.17560
Carrier frequencies of antithrombin, protein C, and protein S deficiency variants estimated using a public database and expression experiments
Keiko Maruyama, Koichi Kokame
Res. Pract. Thromb. Haemost. 5, 179-186 (2021)
https://doi.org/10.1002/rth2.12456
Derlin-3 is required for changes in ERAD complex formation under ER stress
Yuka Eura, Toshiyuki Miyata, Koichi Kokame
Int. J. Mol. Sci. 21, 6146 (2020)
https://doi.org/10.3390/ijms21176146
Success and limitations of plasma treatment in pregnant women with congenital thrombotic thrombocytopenic purpura
Kazuya Sakai, Yoshihiro Fujimura, Yasuyuki Nagata, Satoshi Higasa, Masato Moriyama, Ayami Isonishi, Mutsuko Konno, Michiko Kajiwara, Yoshiyuki Ogawa, Shigehiko Kaburaki, Tomoko Hara, Koichi Kokame, Toshiyuki Miyata, Kinta Hatakeyama, Masanori Matsumoto
Thromb. Haemost. 18, 2929-2941 (2020)
https://doi.org/10.1111/jth.15064
Low-dose activated protein C suppresses the development of cerebral infarction and neurological deficits in mice
Keiko Yamato, Yukako Nakajo, Hitomi Yamamoto-Imoto, Koichi Kokame, Toshiyuki Miyata, Jun C Takahashi, Hiroharu Kataoka, Hiroji Yanamoto
Neurosurg. Open 1, okaa014 (2020)
https://doi.org/10.1093/neuopn/okaa014
Knock-in mice bearing constitutively active αIIb(R990W) mutation develop macrothrombocytopenia with severe platelet dysfunction
Keigo Akuta, Kazunobu Kiyomizu, Hirokazu Kashiwagi, Shinji Kunishima, Nobuko Nishiura, Fumiaki Banno, Koichi Kokame, Hisashi Kato, Yuzuru Kanakura, Toshiyuki Miyata, Yoshiaki Tomiyama
Thromb. Haemost. 18, 497-509 (2020)
https://doi.org/10.1111/jth.14678
Predictive value of protein S-specific activity and ELISA testing in patients with the protein S K196E mutation
Takekazu Miyoshi, Keiko Maruyama, Hisato Oku, Saiko Asahara, Hironori Hanada, Reiko Neki, Jun Yoshimatsu, Koichi Kokame, Toshiyuki Miyata
Thromb. Res. 185, 1-4 (2020)
https://doi.org/10.1016/j.thromres.2019.10.026
Cerebral venous sinus thrombosis associated with protein S deficiency during pregnancy: a case report
Miyu Usui, Tadashi Ozawa, Younhee Kim, Takafumi Mashiko, Kosuke Matsuzono, Keiko Maruyama, Koichi Kokame, Rie Usui, Reiji Koide, Shigeru Fujimoto
Obstet. Gynaecol. 40, 135-136 (2020)
https://doi.org/10.1080/01443615.2019.1606789
Patent ductus arteriosus generates neonatal hemolytic jaundice with thrombocytopenia in Upshaw-Schulman syndrome
Yoshihiro Fujimura, Bernhard Lämmle, Saori Tanabe, Kazuya Sakai, Toshiyuki Kimura, Koichi Kokame, Toshiyuki Miyata, Yukihiro Takahashi, Shigeki Taniguchi, Masanori Matsumoto
Blood Adv. 3, 3191-3195 (2019)
https://doi.org/10.1182/bloodadvances.2019000601
Novel CFHR2-CFHR1 hybrid in C3 glomerulopathy identified by genomic structural variation analysis
Yuka Sugawara, Hideki Kato, Yoko Yoshida, Madoka Fujisawa, Koichi Kokame, Toshiyuki Miyata, Yuko Akioka, Kenichiro Miura, Motoshi Hattori, Masaomi Nangaku
Kidney Int. Rep. 4, 1759-1762 (2019)
https://doi.org/10.1016/j.ekir.2019.09.008
Experience of the use of octreotide for refractory gastrointestinal bleeding in a patient with Jarvik2000 left ventricular assist device
Seiko Nakajima-Doi, Osamu Seguchi, Yasuhiro Shintani, Tomoyuki Fujita, Satsuki Fukushima, Yorihiko Matsumoto, Yuka Eura, Koichi Kokame, Shigeki Miyata, Sachi Matsuda, Hiroki Mochizuki, Keiichiro Iwasaki, Yuki Kimura, Koichi Toda, Yuto Kumai, Kensuke Kuroda, Takuya Watanabe, Masanobu Yanase, Junjiro Kobayashi, Norihide Fukushima
Artif. Organs 22, 334-337 (2019)
https://doi.org/10.1007/s10047-019-01121-7
Effects of low-dose combined oral contraceptives and protein S K196E mutation on anticoagulation factors: a prospective observational study
Takekazu Miyoshi, Hisato Oku, Saiko Asahara, Akira Okamoto, Koichi Kokame, Michikazu Nakai, Kunihiro Nishimura, Fumiyuki Otsuka, Aya Higashiyama, Jun Yoshimatsu, Toshiyuki Miyata
Int. J. Hematol. 109, 641-649 (2019)
https://doi.org/10.1007/s12185-019-02633-x
The international hereditary thrombotic thrombocytopenic purpura (TTP) registry: Key findings at enrolment until 2017
Anette van Dorland, Magnus Mansouri Taleghani, Kazuya Sakai, Kenneth D. Friedman, James N. George, Ingrid Hrachovinova, Paul N. Knöbl, Anne Sophie von Krogh, Reinhard Schneppenheim, Isabella Aebi-Huber, Lukas Bütikofer, Carlo R. Largiadèr, Zuzana Cermakova, Koichi Kokame, Toshiyuki Miyata, Hideo Yagi, Deirdra R. Terrell, Sara K. Veseley, Masanori Matsumoto, Bernhard Lämmle, Yoshihiro Fujimura, Johanna A. Kremer Hovinga; Hereditary TTP Registry
Haematologica 104, 2107-2115 (2019)
https://doi.org/10.3324/haematol.2019.216796
Functional regulation of von Willebrand factor ameliorates acute ischemia-reperfusion kidney injury in mice
Shiro Ono, Hideto Matsui, Masashi Noda, Shogo Kasuda, Noritaka Yada, Kiyomi Yoshimoto, Masashi Akiyama, Toshiyuki Miyata, Mitsuhiko Sugimoto, Kenji Nishio
Sci. Rep. 9, 14453 (2019)
https://doi.org/10.1038/s41598-019-51013-2
Acquired von Willebrand syndrome associated with cardiovascular diseases
Hisanori Horiuchi, Tsuyoshi Doman, Koichi Kokame, Yoshikatsu Saiki, Masanori Matsumoto
Atheroscler. Thromb. 26, 303-314 (2019)
https://doi.org/10.5551/jat.RV17031
Upshaw-Schulman syndrome diagnosed during pregnancy complicated by reversible cerebral vasoconstriction syndrome
Mariko Tsuda, Motoaki Shiratsuchi, Motohiko Ikeda, Masanori Matsumoto, Yoshihiro Fujimura, Koichi Kokame, Takamitsu Matsushima, Yasuhiro Nakashima, Yoshihiro Ogawa
Transfus. Apher. Sci. 57, 790-792 (2018)
https://doi.org/10.1016/j.transci.2018.10.023
Protein S K196E mutation reduces its cofactor activity for APC but not for TFPI
Keiko Maruyama, Masashi Akiyama, Toshiyuki Miyata, Koichi Kokame
Res. Pract. Thromb. Haemost. 2, 751-756 (2018)
https://doi.org/10.1002/rth2.12152
Clinical characteristics and genetic backgrounds of Japanese patients with atypical hemolytic uremic syndrome
Madoka Fujisawa, Hideki Kato, Yoko Yoshida, Tomoko Usui, Munenori Takata, Mika Fujimoto, Hideo Wada, Yumiko Uchida, Koichi Kokame, Masanori Matsumoto, Yoshihiro Fujimura, Toshiyuki Miyata, Masaomi Nangaku
Clin. Exp. Nephrol. 22, 1088-1099 (2018)
https://doi.org/10.1007/s10157-018-1549-3
Herpud1 impacts insulin-dependent glucose uptake in skeletal muscle cells by controlling the Ca2+-calcineurin-Akt axis
Mario Navarro-Marquez, Natalia Torrealba, Rodrigo Troncoso, Cesar Vasquez-Trincado, Marcelo Rodriguez, Pablo E Morales, Elisa Villalobos, Yuka Eura, Lorena Garcia, Mario Chiong, Amira Klip, Enrique Jaimovich, Koichi Kokame, Sergio Lavandero
Biochim. Biophys. Acta Mol. Basis Dis. 1864, 1653-1662 (2018)
https://doi.org/10.1016/j.bbadis.2018.02.018
Congenital coagulation factor X deficiency: Genetic analysis of five patients and functional characterization of mutant factor X proteins
Satomi Nagaya, Masashi Akiyama, Morika Murakami, Akiko Sekiya, Hidesaku Asakura, Eriko Morishita
Hemophilia 24, 774-785 (2018)
https://doi.org/10.1111/hae.13606
von Willebrand factor aggravates hepatic ischemia-reperfusion injury by promoting neutrophil recruitment in mice
Yasuyuki Urisono, Asuka Sakata, Hideto Matsui, Shogo Kasuda, Shiro Ono, Kiyomi Yoshimoto, Kenji Nishio, Masayuki Sho, Masashi Akiyama, Toshiyuki Miyata, Kazuo Okuchi, Satoshi Nishimura, Mitsuhiko Sugimoto
Thromb Haemost 118, 700-708 (2018)
https://doi.org/10.1055/s-0038-1636529
last updated : 2024/04/09