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Organismal Biosystems Laboratories

Laboratory of Immunology and Cell Biology

Prof. ISHII Masaru Prof. ISHII Masaru

Keywords：

Imaging, Immunity, Bone tissue, Bone marrow, Blood cell

Living cells are constantly moving and working in our living bodies

The main theme of our laboratory is to reveal the cellular dynamics in various kinds of tissues and organs in vivo, by using advanced imaging techniques, especially focusing on the dynamic phenomenon in immune and inflammatory systems. By exploiting advanced multiphoton microscopy, we have originally developed original intravital imaging systems that enable the visualization of the movements of the diverse cell types resident in various immune tissues and organs in situ. We first established a live imaging system for visualizing living phenomena in intact bone marrow cavities. The dynamic nature of different cell types can be visualized in a time-dependent manner, in addition to the spatial and structural information generated by conventional histological analyses, resulting in a paradigm shift in research on immunology and cell biology.

Dynamic immune network wiring different tissues and organs and constituting integrity of biosystems

Members

Masaru Ishii (Professor) mishii[at]icb.med.osaka-u.ac.jp
Yasuhito Yahara (Associate Professor) yyahara[at]icb.med.osaka-u.ac.jp
Yutaka Uchida (Assistant Professor) uchida[at]icb.med.osaka-u.ac.jp
kentaro fujii (Assistant Professor, Graduate School of Medicine) key.fuji[at]icb.med.osaka-u.ac.jp

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Q＆A

What is your hot research topic?
Organisms, such as animals, are shaped by organizational dynamics, and the spatiotemporal control of dynamic cellular movement in the body is crucial for life activity. In our lab, we intend to comprehensively investigate dynamic behaviors and their molecular basis in vivo using combinatory cutting-edge technologies, such as intravital imaging and single-cell sequencing analyses that were originally developed by the proposer of this study. Drawing on novel cross-disciplinary approaches based on mathematics, and bioinformatics, we seek to understand the essence of life by identifying the invisible hand ruling cellular dynamics in vivo.
What is your recent breakthrough or research progress?
1. Osteoclasts have a unique bone-destroying capacity, playing key roles in steady-state bone remodeling and arthritic bone erosion. Whether the osteoclasts in these different tissue settings arise from the same precursor states of monocytoid cells is presently unknown. Here, we show that osteoclasts in pannus originate exclusively from circulating bone marrow-derived cells and not from locally resident macrophages. We identify murine CX3CR1hiLy6CintF4/80+I-A+/I-E+ macrophages (termed here arthritis-associated osteoclastogenic macrophages (AtoMs)) as the osteoclast precursor-containing population in the inflamed synovium, comprising a subset distinct from conventional osteoclast precursors in homeostatic bone remodeling. Tamoxifen-inducible Foxm1 deletion suppressed the capacity of AtoMs to differentiate into osteoclasts in vitro and in vivo. Furthermore, synovial samples from human patients with rheumatoid arthritis contained CX3CR1+HLA-DRhiCD11c+CD80-CD86+ cells that corresponded to mouse AtoMs, and human osteoclastogenesis was inhibited by the FoxM1 inhibitor thiostrepton, constituting a potential target for rheumatoid arthritis treatment.（Hasegawa et al., Nat Immunol, 2019）
2. Bone homeostasis is regulated by communication between bone-forming mature osteoblasts (mOBs) and bone-resorptive mature osteoclasts (mOCs). However, the spatial-temporal relationship and mode of interaction in vivo remain elusive. Here we show, by using an intravital imaging technique, that mOB and mOC functions are regulated via direct cell-cell contact between these cell types. The mOBs and mOCs mainly occupy discrete territories in the steady state, although direct cell-cell contact is detected in spatiotemporally limited areas. In addition, a pH-sensing fluorescence probe reveals that mOCs secrete protons for bone resorption when they are not in contact with mOBs, whereas mOCs contacting mOBs are non-resorptive, suggesting that mOBs can inhibit bone resorption by direct contact. Intermittent administration of parathyroid hormone causes bone anabolic effects, which lead to a mixed distribution of mOBs and mOCs, and increase cell-cell contact. This study reveals spatiotemporal intercellular interactions between mOBs and mOCs affecting bone homeostasis in vivo.（Furuya et al., Nat Commun, 2018）。
3. Metabolic reprogramming occurs in response to the cellular environment to mediate differentiation, but the fundamental mechanisms linking metabolic processes to differentiation programs remain to be elucidated. During osteoclast differentiation, a shift toward more oxidative metabolic processes occurs. In this study we identified the de novo DNA methyltransferase 3a (Dnmt3a) as a transcription factor that couples these metabolic changes to osteoclast differentiation. We also found that receptor activator of nuclear factor-κB ligand (RANKL), an essential cytokine for osteoclastogenesis, induces this metabolic shift towards oxidative metabolism, which is accompanied by an increase in S-adenosylmethionine (SAM) production. We found that SAM-mediated DNA methylation by Dnmt3a regulates osteoclastogenesis via epigenetic repression of anti-osteoclastogenic genes. The importance of Dnmt3a in bone homeostasis was underscored by the observations that Dnmt3a-deficient osteoclast precursor cells do not differentiate efficiently into osteoclasts and that mice with an osteoclast-specific deficiency in Dnmt3a have elevated bone mass due to a smaller number of osteoclasts. Furthermore, inhibition of DNA methylation by theaflavin-3,3'-digallate abrogated bone loss in models of osteoporosis. Thus, this study reveals the role of epigenetic processes in the regulation of cellular metabolism and differentiation, which may provide the molecular basis for a new therapeutic strategy for a variety of bone disorders.(Nishikawa et al., Nat Med, 2015)
What kind of background do your lab members have？
We have a variety of members, including graduates from the areas of science and medicine.
Do you collaborate with other institutions and universities?
We are in collaboration with the Graduate School of Information Science and Technology and the Graduate School of Engineering at Osaka University. We are also studying with a variety of research institutions, such as the University of Tokyo, Kyoto University, and RIKEN.
What kind of careers do your Lab's alumni go on to?
Academic positions (Osaka University), pharmaceutical companies, etc
How do you develop your research?
The ultimate aim of the proposed research is to expand the concept of morphology, which is based on the form of cells and tissue, and to establish a novel scientific field, which posits cellular movement as the universal principle of life.

Research Highlights

Publications (Research Articles, Reviews, Books)

2021

Akito Morimoto, Junichi Kikuta, Keizo Nishikawa, Takao Sudo, Maki Uenaka, Masayuki Furuya, Tetsuo Hasegawa, Kunihiko Hashimoto, Hiroyuki Tsukazaki, Shigeto Seno, Akira Nakamura, Daisuke Okuzaki, Fuminori Sugihara, Akinori Ninomiya, Takeshi Yoshimura, Ryoko Takao-Kawabata, Hideo Matsuda, Masaru Ishii

SLPI is a critical mediator that controls PTH-induced bone formation

Nature Communications 12(1):2136  2021 （PMID：33837198 DOI：10.1038/s41467-021-22402-x）

Takao Sudo, Yasutaka Motomura, Daisuke Okuzaki, Tetsuo Hasegawa, Takafumi Yokota, Junichi Kikuta, Tomoka Ao, Hiroki Mizuno, Takahiro Matsui, Daisuke Motooka, Ryosuke Yoshizawa, Takashi Nagasawa, Yuzuru Kanakura, Kazuyo Moro, Masaru Ishii

Group 2 innate lymphoid cells support hematopoietic recovery under stress conditions

Journal of Experimental Medicine 218(5):e20200817  2021 （PMID：33666647 DOI：10.1084/jem.20200817）

2020

Hashimoto K, Kaito T, Furuya M, Seno S, Okuzaki D, Kikuta J, Tsukazaki H, Matsuda H, Yoshikawa H, Ishii M

In vivo dynamic analysis of BMP-2-induced ectopic bone formation

Sci Rep 10(1):4751  2020 （PMID：32179857 DOI：10.1038/s41598-020-61825-2）

Morimoto A, Kikuta J, Ishii M

Intravital multiphoton microscopy as a novel tool in the field of immunopharmacology.

Pharmacol. Ther. 206:107429  2020 （PMID：31689449 DOI：10.1016/j.pharmthera.2019.107429）

Nishizawa S, Kikuta J, Seno S, Kajiki M, Tsujita R, Mizuno H, Sudo T, Ao T, Matsuda H, Ishii M

Thrombomodulin induces anti-inflammatory effects by inhibiting the rolling adhesion of leukocytes in vivo.

Pharmacol. Sci. 143(1):17-22  2020 （PMID：32122774 DOI：10.1016/j.jphs.2020.01.001）

2019

Hasegawa T, Kikuta J, Sudo T, Matsuura Y, Matsui T, Simmons S, Ebina K, Hirao M, Okuzaki D, Yoshida Y, Hirao A, Kalinichenko VV, Yamaoka K, Takeuchi T, Ishii M

Identification of a novel arthritis-associated osteoclast precursor macrophage regulated by FoxM1

Nat. Immunol. 20(12):1631-1643  2019 （PMID：31740799 DOI：10.1038/s41590-019-0526-7）

Kojima Y, Tsuchiya A, Ogawa M, Nojiri S, Takeuchi S, Watanabe T, Nakajima K, Hara Y, Yamashita J, Kikuta J, Takamura M, Ishii M, Terai S

Mesenchymal stem cells cultured under hypoxic conditions had a greater therapeutic effect on mice with liver cirrhosis compared to those cultured under normal oxygen conditions.

Regen. Ther. 11:269-281  2019 （PMID：31667206 DOI：10.1016/j.reth.2019.08.005）

Osato N, Shigeta H, Seno S, Uchida Y, Kikuta J, Ishii M, Matsuda H

Single-cell Transcriptome Analysis of Mouse Leukocytes in Inflammatory Stimulation

2019 IEEE International Conference on Bioinformatics and Biomedicine (BIBM)   2019 （ DOI：10.1109/BIBM47256.2019.8983394）

Shigeta H, Seno S, Nishizawa S, Uchida Y, Kikuta J, Ishii M, H Matsuda

Analyzing Leukocyte Migration Trajectories by Deformable Image Matching

2019 IEEE 19th International Conference on Bioinformatics and Bioengineering (BIBE)   2019 （ DOI：10.1109/BIBE.2019.00025）

Minoshima M, Kikuta J, Omori Y, Seno S, Suehara R, Maeda H, Matsuda H, Ishii M, Kikuchi K

In Vivo Multicolor Imaging with Fluorescent Probes Revealed the Dynamics and Function of Osteoclast Proton Pumps.

ACS Central Sci. 5(6):1059-1066  2019 （PMID：31263765 DOI：10.1021/acscentsci.9b00220）

Morita N, Umemoto E, Fujita S, Hayashi A, Kikuta J, Kimura I, Haneda T, Imai T, Inoue A, Mimuro H, Maeda Y, Kayama H, Okumura R, Aoki J, Okada N, Kida T, Ishii M, Nabeshima R, Takeda K

GPR31-dependent dendrite protrusion of intestinal CX3CR1+ cells by bacterial metabolites

Nature 566(7742):110-114  2019 （PMID：30675063 DOI：10.1038/s41586-019-0884-1）

Simmons S, Sasaki N, Umemoto E, Uchida Y, Fukuhara S, Kitazawa Y, Okudaira M, Inoue A, Tohya K, Aoi K, Aoki J, Mochizuki N, Matsuno K, Takeda K, Miyasaka M, Ishii M

High-endothelial cell-derived S1P regulates dendritic cell localization and vascular integrity in the lymph node.

eLife 8:e41239  2019 （PMID：31570118 DOI：10.7554/eLife.41239）

Watanabe Y, Tsuchiya A, Seino S, Kawata Y, Kojima Y, Ikarashi S, Lewis PJS, Lu W-Y, Kikuta J, Kawai H, Yamagiwa S, Forbes SJ, Ishii M, Terai S

Mesenchymal stem cells and induced bone marrow-derived macrophages synergistically improve liver fibrosis in mice.

Stem Cells Transl. Med. 8(3):271-284  2019 （PMID：30394698 DOI：10.1002/sctm.18-0105）

Hasegawa T, Kikuta J, Ishii M

Imaging the Bone-Immune Cell Interaction in Bone Destruction.

Front. Immunol. 0.830555556  2019 （PMID：30972080 DOI：10.3389/fimmu.2019.00596）

2018

Baba M, Endoh M, Ma W, Toyama H, Hirayama A, Nishikawa K, Takubo K, Hano H, Hasumi H, Umemoto T, Hashimoto M, Irie N, Esumi C, Kataoka M, Nakagata N, Soga T, Yao M, Kamba T, Minami T, Ishii M, Suda T

Folliculin Regulates Osteoclastogenesis Through Metabolic Regulation.

J. Bone Miner. Res. 33(10):1785-98  2018 （PMID：29893999 DOI：10.1002/jbmr.3477）

Tanaka Y, Sabharwal L, Ota M, Nakagawa I, Jiang JJ, Arima Y, Ogura H, Okochi M, Ishii M, Kamimura D, Murakami M

Presenilin 1 regulates NF-κB activation via association with breakpoint cluster region and casein kinase II.

J. Immunol. 201(8):2256-2263  2018 （PMID：30201812 DOI：10.4049/jimmunol.1701446）

Matsuura R, Miyagawa S, Fukushima S, Goto T, Harada A, Shimozaki Y, Yamaki K, Sanami S, Kikuta J, Ishii M, Sawa Y

Intravital imaging with two-photon microscopy reveals cellular dynamics in the ischeamia-reperfused rat heart.

Sci Rep 8(1):15991  2018 （PMID：30375442 DOI：10.1038/s41598-018-34295-w）

Kikuta J, Shirazaki M, Sudo T, Mizuno H, Morimoto A, Suehara R, Minoshima M, Kikuchi K, Ishii M

Dynamic analyses of the short-term effects of different bisphosphonates using intravital two-photon microscopy.

JBMR Plus. 2(6):362-366  2018 （PMID：30460339 DOI：10.1002/jbm4.10057）

Sakaguchi Y, Nishikawa K, Seno S, Matsuda H, Takayanagi H, Ishii M

Roles of Enhancer RNAs in RANKL-induced Osteoclast Differentiation Identified by Genome-wide Cap-analysis of Gene Expression using CRISPR/Cas9.

Sci Rep 14(1):7504  2018 （PMID：29760402 DOI：10.1038/s41598-018-25748-3）

Das P, Veazey KJ, Van HT, Kaushik S, Lin K, Lu Y, Ishii M, Kikuta J, Ge K, Nussenzweig A, Santos MA

Histone methylation regulator PTIP is required to maintain normal and leukemic bone marrow niches.

Proc. Natl. Acad. Sci. U. S. A. 115(43):E10137-E10146  2018 （PMID：30297393 DOI：10.1073/pnas.1806019115）

Matsuura Y, Kikuta J, Kishi Y, Hasegawa T, Okuzaki D, Hirano T, Minoshima M, Kikuchi K, Kumanogoh A, Ishii M

In vivo visualisation of different modes of action of biological DMARDs inhibiting osteoclastic bone resorption.

Ann. Rheum. Dis. 77(8):1219-1225  2018 （PMID：29705743 DOI：10.1136/annrheumdis-2017-212880）

Inaki M, Hatori R, Nakazawa N, Okumura T, Ishibashi T, Kikuta J, Ishii M, Matsuno K, Honda H

Chiral cell sliding drives left-right asymmetric organ twisting.

eLife 7:e32506  2018 （PMID：29891026 DOI：10.7554/eLife.32506）

Doi Y, Yokota T, Satoh Y, Okuzaki D, Tokunaga M, Ishibashi T, Sudo T, Ueda T, Shingai Y, Ichii M, Tanimura A, Ezoe S, Shibayama H, Kohwi-Shigematsu T, Takeda　J, Oritani K, Kanakura Y

Variable SATB1 Levels Regulate Hematopoietic Stem Cell Heterogeneity with Distinct Lineage Fate.

Cell Reports 23(11):3223-3235  2018 （PMID：29898394 DOI：10.1016/j.celrep.2018.05.042）

Ueda Y, Ishiwata T, Shinji S, Arai T, Matsuda Y, Aida J, Sugimoto N, Okazaki T, Kikuta J, Ishii M, Sato M

In vivo imaging of T cell lymphoma infiltration process at the colon.

Sci Rep 8(1):3978.  2018 （PMID：29507328 DOI：10.1038/s41598-018-22399-2）

Matsuura R, Miyagawa S, Kikuta J, Ishii M, Sawa Y

Intravital Imaging of the Heart at the Cellular Level Using Two-Photon Microscopy.

Methods Mol Biol. 1763:145-151  2018 （PMID：29476496 DOI：10.1007/978-1-4939-7762-8_14）

Matsumoto S, Kikuta J, Ishii M

Intravital Imaging of Liver Cell Dynamics.

Methods Mol Biol. 1763:137-143  2018 （PMID：29476495 DOI：10.1007/978-1-4939-7762-8_13）

Kikuta J, Ishii M

Bone Imaging: Osteoclast and Osteoblast Dynamics.

Methods Mol Biol. 1763:1-9  2018 （PMID：29476483 DOI：10.1007/978-1-4939-7762-8_1）

Sudo T, Mizuno H

Dynamic analysis of hematopoietic stem cells in the bone marrow by intravital imaging.

Clin Calcium. 28(2):231-236  2018 （PMID：29371489 ）

Uenaka M, Mizuno H, Ishii M

In vivo imaging of osteoblasts.

Biol. Reprod. 28(2):217-222  2018 （PMID：29371487 ）

Mizuno H, Ishii M

Development of methodology for living bone imaging.

Biomaterials 28(2):181-185  2018 （PMID：29371482 ）

Mizuno H, Kikuta J, Ishii M

In vivo live imaging of bone cells.

Histochem. Cell Biol. 149(4):417-422  2018 （PMID：29362895 DOI：10.1007/s00418-018-1638-0）

Furuya M, Kikuta J, Fujimori S, Seno S, Maeda H, Shirazaki M, Uenaka M, Mizuno H, Iwamoto Y,　Morimoto A,　Hashimoto K, Ito T, Isogai Y, Kashii M, Kaito T, Ohba S, Chung Ui, Lichtler AC, Kikuchi K, Matsuda H, Yoshikawa H, Ishii M

Direct cell-cell contact between mature osteoblasts and osteoclasts dynamically controls their functions in vivo.

Biomolecules 9(1):300  2018 （PMID：29352112 DOI：10.1038/s41467-017-02541-w）

Ishibashi T, Yokota T, Satoh Y, Ichii M, Sudo T, Doi Y, Ueda T, Nagate Y, Hamanaka Y, Tanimura A, Ezoe S, Shibayama H, Oritani K, Kanakura Y

Identification of MS4A3 as a reliable marker for early myeloid differentiation in human hematopoiesis.

Biophys. J. 495(3):2338-2343  2018 （PMID：29274779 DOI：10.1016/j.bbrc.2017.12.117）

2017

Nagatake T, Shiogama Y, Inoue A, Kikuta J, Honda T, Tiwari P, Yanagisawa A, Isobe Y, Matsumoto N, Shimojou M, Morimoto S, Suzuki H, Hirata S, Steneberg P, Edlund H, Aoki J, Arita M, Kiyono H, Yasutomi Y, Ishii M, Kabashima K, Kunisawa J

The 17,18-epoxyeicosatetraenoic acid-G protein-coupled receptor 40 axis ameliorates contact hypersensitivity by inhibiting neutrophil mobility in mice and cynomolgus macaques.

J. Allergy Clin. Immunol. 142(2):470-484  2017 （PMID：29288079 DOI：10.1016/j.jaci.2017.09.053）

Ishii M

Imaging of inflammation and regeneration: a novel trend dissecting dynamic features of biological phenomena in vivo.

Inflamm Regen. 37:26:00  2017 （PMID：29259725 DOI：10.1186/s41232-017-0057-2）

Yamaga K, Murota H, Tamura A, Miyata H, Ohmi M, Kikuta J, Ishii M, Tsukita S, Katayama I

Claudin-3 Loss Causes Leakage of Sweat from the Sweat Gland to Contribute to the Pathogenesis of Atopic Dermatitis.

J. Invest. Dermatol. 138(6):1279-1287  2017 （PMID：29277540 DOI：10.1016/j.jid.2017.11.040）

Ao T, Kikuta J, Ishii M

Update on recent progress in vitamin D research. The effects of vitamin D in autoinflammatory diseases.

Clin Calcium. 27(11):1551-1559  2017 （PMID：29074827 ）

Sato Y, Uchida Y, Hu J, Young-Pearse TL, Niikura T, Mukouyama YS

Soluble APP functions as a vascular niche signal that controls adult neural stem cell number.

Development 144:2730-2736  2017 （PMID：28694255 DOI：10.1242/dev.143370）

Kon S, Ishibashi K, Katoh H, Kitamoto S, Shirai T, Tanaka S, Kajita M, Ishikawa S, Yamauchi H, Yako Y, Kamasaki T, Matsumoto T, Watanabe H, Egami R, Sasaki A, Nishikawa A, Kameda I, Maruyama T, Narumi R, Morita T, Sasaki Y, Enoki R, Honma S, Imamura H, Oshima M, Soga T, Miyazaki JI, Duchen MR, Nam JM, Onodera Y, Yoshioka S, Kikuta J, Ishii M, Imajo M, Nishida E, Fujioka Y, Ohba Y, Sato T, Fujita Y

Cell competition with normal epithelial cells promotes apical extrusion of transformed cells through metabolic changes.

Nat. Cell Biol. 19(5):530-541  2017 （PMID：28414314 DOI：10.1038/ncb3509）

Matsui T, Mizuno H, Sudo T, Kikuta J, Haraguchi N, Ikeda JI, Mizushima T, Yamamoto H, Morii E, Mori M, Ishii M

Non-labeling multiphoton excitation microscopy as a novel diagnostic tool for discriminating normal tissue and colorectal cancer lesions.

Sci Rep 7(1):6959  2017 （PMID：28761050 DOI：10.1038/s41598-017-07244-2）

Shigeta H, Mashita T, Kikuta J, Seno S, Takemura H1, Ishii M, Matsuda H

Bone marrow cavity segmentation using graph-cuts with wavelet-based texture feature.

J. Bioinform. Comput. Biol. 15(5):1740004  2017 （PMID：28877645 DOI：10.1142/S0219720017400042）

Miyachi Y, Tsuchiya K, Komiya C, Shiba K, Shimazu N, Yamaguchi S, Deushi M, Osaka M, Inoue K, Sato Y, Matsumoto S, Kikuta J, Wake K, Yoshida M, Ishii M, Ogawa Y

Roles of cell-cell adhesion and contact in obesity-induced hepatic myeloid cell accumulation and glucose intolerance.

Cell Reports 18(11):2766-2779  2017 （PMID：28297678 DOI：10.1016/j.celrep.2017.02.039）

Ishii M

Immunology provides a great success for treating systemic autoimmune diseases - a perspective on immunopharmacology - IUPHAR Review X.

Br. J. Pharmacol. 174(13):1875-1880  2017 （PMID：28299772 DOI：10.1111/bph.13784）

2016

Ishii M

Intravital imaging technology reveals immune system dynamics in vivo.

Allergol. Int. 65(3):225-227  2016 （PMID：27238377 DOI：10.1016/j.alit.2016.05.001）

Ishibashi T, Yokota T, Tanaka H, Ichii M, Sudo T, Satoh Y, Doi Y, Ueda T, Tanimura A, Hamanaka Y, Ezoe S, Shibayama H, Oritani K, Kanakura Y

ESAM is a novel human hematopoietic stem cell marker associated with a subset of human leukemias.

Exp. Hematol. 44(4):269-281  2016 （PMID：26774386 DOI：10.1016/j.exphem.2015.12.010）

Sudo T, Yokota T, Okuzaki D, Ueda T, Ichii M, Ishibashi T, Isono T, Habuchi Y, Oritani K, Kanakura Y

Endothelial Cell-Selective Adhesion Molecule Expression in Hematopoietic Stem/Progenitor Cells Is Essential for Erythropoiesis Recovery after Bone Marrow Injury.

PLoS One 11(4):e0154189.  2016 （PMID：27111450 DOI：10.1371/journal.pone.0154189）

Lim BC, Matsumoto S, Yamamoto H, Mizuno H, Kikuta J, Ishii M, Kikuchi A

Prickle1 promotes focal adhesion disassembly in cooperation with the CLASP-LL5β complex in migrating cells.

J. Cell Sci. 129(16):3115-29.  2016 （PMID：27378169 DOI：10.1242/jcs.185439）

Mizuno H, Yamashita E, Ishii M

Analysis of bone tissues by intravital imaging

Clin Calcium. 26(5):729-34  2016 （PMID：27117619 ）

Iwamoto Y, Nishikawa K, Imai R, Furuya M, Uenaka M, Ohta Y, Morihana T, Ochi S, Penninger JM , Katayama I, Inohara I, Ishii M

Intercellular communication between keratinocytes and fibroblasts induces local osteoclast differentiation: a mechanism underlying cholesteatoma-induced bone destruction.

Mol. Cell. Biol. 36(11):1610-20.  2016 （PMID：27001307 DOI：10.1128/MCB.01028-15）

Otani K, Naito Y, Sakaguchi Y, Seo Y, Takahashi Y, Kikuta J, Ogawa K, Ishii M

Cell-cycle-controlled radiation therapy was effective for treating a murine malignant melanoma cell line in vitro and in vivo.

Sci Rep 6:30689  2016 （PMID：27480052 DOI：10.1038/srep30689）

Sugimoto K, Miyata Y, Nakayama T, Saito S, Suzuki R, Hayakawa F, Nishiwaki S, Mizuno H, Takeshita K, Kato H, Ueda R, Takami A, Naoe T

Fibroblast Growth Factor-2 facilitates the growth and chemo-resistance of leukemia cells in the bone marrow by modulating osteoblast functions.

Sci Rep 6:30779  2016 （PMID：27481339 DOI：10.1038/srep30779）

Maeda H, Kowada T, Kikuta J, Furuya M, Shirazaki M, Mizukami S, Ishii M, Kikuchi K

Real-time intravital imaging of pH variation associated with cell osteoclast activity and motility using designed small molecular probe.

Nat. Chem. Biol. 12(8):579-85  2016 （PMID：27272564 DOI：10.1038/nchembio.2096）

Yoshikawa S, Usami T, Kikuta J, Ishii M, Sasano T, Sugiyama K, Furukawa T, Nakasho E, Takayanagi H, Tedder TF, Karasuyama H, Miyawaki A, Adachi T

Intravital imaging of Ca(2+) signals in lymphocytes of Ca(2+) biosensor transgenic mice: indication of autoimmune diseases before the pathological onset.

Sci Rep 6:18738  2016 （PMID：26732477 DOI：10.1038/srep18738）

Takeda A, Kobayashi D, Aoi K, Sasaki N, Sugiura Y, Igarashi H, Tohya K, Inoue A, Hata E, Akahoshi N, Hayasaka H, Kikuta J, Scandella E, Ludewig B, Ishii S, Aoki J, Suematsu M, Ishii M, Takeda K, Jalkanen S, Miyasaka M, Umemoto E

Fibroblastic reticular cell-derived lysophosphatidic acid regulates confined intranodal T-cell motility.

eLife 5:e10561  2016 （PMID：26830463 DOI：10.7554/eLife.10561）

Kikuta J, Nevius E, Ishii M, Pereira JP

Trafficking of Osteoclast Precursors

Osteoimmunology (Second Edition) 25-40  2016 （ DOI：10.1016/B978-0-12-800571-2.00003-7）

Our ideal candidate (as a graduate student)

We are looking for a highly motivated person to work on our research topics as our lab member. Our lab welcomes the person who loves taking care of creatures, hand working and handcraft too. Any kind of background (such as your expertise or major) is available.

Contact

Laboratory of Immunology and Cell Biology, Graduate School of Frontier Biosciences, Osaka University,
2-2 Yamadaoka, Suita, Osaka 565-0871 Japan.

TEL: +81-6-6879-3881

E-mail: mishii[at]icb.med.osaka-u.ac.jp (Prof. Masaru Ishii)

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