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MURATA YojiGraduate School of Medicine / Faculty of Medical SciencesAssociate Professor
Research activity information
■ Award- Oct. 2016 神戸大学, 平成27年度神戸大学医学部優秀学術論文賞, Protein tyrosine phosphatase SAP-1 protects against colitis through regulation of CEACAM20 in the intestinal epitheliumOthers
- Tumor-associated macrophages (TAMs) are abundant in the tumor microenvironment and are considered potential targets for cancer immunotherapy. To examine the antitumor effects of agents targeting human TAMs in vivo, we here established preclinical tumor xenograft models based on immunodeficient mice that express multiple human cytokines and have been reconstituted with a human immune system by transplantation of human CD34+ hematopoietic stem and progenitor cells (HIS-MITRG mice). HIS-MITRG mice supported the growth of both human cell line (Raji)– and patient-derived B cell lymphoma as well as the infiltration of human macrophages into their tumors. We examined the potential antitumor action of an antibody to human SIRPα (SE12C3) that inhibits the interaction of CD47 on tumor cells with SIRPα on human macrophages and thereby promotes Fcγ receptor–mediated phagocytosis of the former cells by the latter. Treatment with the combination of rituximab (antibody to human CD20) and SE12C3 inhibited Raji tumor growth in HIS-MITRG mice to a markedly greater extent than did rituximab monotherapy. This enhanced antitumor effect was dependent on human macrophages and attributable to enhanced rituximab-dependent phagocytosis of lymphoma cells by human macrophages. Treatment with rituximab and SE12C3 also induced reprogramming of human TAMs toward a proinflammatory phenotype. Furthermore, the combination treatment essentially prevented the growth of patient-derived diffuse large B cell lymphoma in HIS-MITRG mice. Our findings thus support the study of HIS-MITRG mice as a model for the preclinical evaluation in vivo of potential therapeutics, such as antibodies to human SIRPα, that target human TAMs.Frontiers Media SA, Dec. 2023, Frontiers in Immunology, 14, English, International magazine[Refereed]Scientific journal
- Accumulation of lipotoxic lipids, such as free cholesterol, induces hepatocyte death and subsequent inflammation and fibrosis in the pathogenesis of nonalcoholic steatohepatitis (NASH). However, the underlying mechanisms remain unclear. We have previously reported that hepatocyte death locally induces phenotypic changes in the macrophages surrounding the corpse and remnant lipids, thereby promoting liver fibrosis in a murine model of NASH. Here, we demonstrated that lysosomal cholesterol overload triggers lysosomal dysfunction and profibrotic activation of macrophages during the development of NASH. β-cyclodextrin polyrotaxane (βCD-PRX), a unique supramolecule, is designed to elicit free cholesterol from lysosomes. Treatment with βCD-PRX ameliorated cholesterol accumulation and profibrotic activation of macrophages surrounding dead hepatocytes with cholesterol crystals, thereby suppressing liver fibrosis in a NASH model, without affecting the hepatic cholesterol levels. In vitro experiments revealed that cholesterol-induced lysosomal stress triggered profibrotic activation in macrophages predisposed to the steatotic microenvironment. This study provides evidence that dysregulated cholesterol metabolism in macrophages would be a novel mechanism of NASH.Nov. 2023, The Journal of experimental medicine, 220(11) (11), English, International magazineScientific journal
- Conventional dendritic cells (cDCs) are required for peripheral T cell homeostasis in lymphoid organs, but the molecular mechanism underlying this requirement has remained unclear. We here show that T cell–specific CD47-deficient ( Cd47 ΔT ) mice have a markedly reduced number of T cells in peripheral tissues. Direct interaction of CD47-deficient T cells with cDCs resulted in activation of the latter cells, which in turn induced necroptosis of the former cells. The deficiency and cell death of T cells in Cd47 ΔT mice required expression of its receptor signal regulatory protein α on cDCs. The development of CD4 + T helper cell–dependent contact hypersensitivity and inhibition of tumor growth by cytotoxic CD8 + T cells were both markedly impaired in Cd47 ΔT mice. CD47 on T cells thus likely prevents their necroptotic cell death initiated by cDCs and thereby promotes T cell survival and function.Proceedings of the National Academy of Sciences, Aug. 2023, Proceedings of the National Academy of Sciences, 120(33) (33)Scientific journal
- (有)科学評論社, Mar. 2023, 腫瘍内科, 31(3) (3), 327 - 333, Japanese【新しいがん免疫療法研究の展開と臨床応用】自然免疫制御を介したがん免疫療法の進展 CD47-SIRPα経路の制御によるがん免疫療法
- Feb. 2023, Cancer scienceScientific journal
- Conventional dendritic cells (cDCs) orchestrate immune responses to cancer and comprise two major subsets: type-1 cDCs (cDC1s) and type-2 cDCs (cDC2s). Compared with cDC1s, which are dedicated to the activation of CD8+ T cells, cDC2s are ontogenically and functionally heterogeneous, with their main function being the presentation of exogenous antigens to CD4+ T cells for the initiation of T helper cell differentiation. cDC1s play an important role in tumor-specific immune responses through cross-presentation of tumor-derived antigens for the priming of CD8+ T cells, whereas little is known of the role of cDC2s in tumor immunity. Recent studies have indicated that human cDC2s can be divided into at least two subsets and have implicated these cells in both anti- and pro-tumoral immune responses. Furthermore, the efficacy of cDC2-based vaccines as well as cDC2-targeted therapeutics has been demonstrated in both mouse models and human patients. Here we summarize current knowledge about the role of cDC2s in tumor immunity and address whether these cells are beneficial in the context of antitumor immune responses.Apr. 2022, Cancers, 14(8) (8), English, International magazineScientific journal
- The interaction of signal regulatory protein α (SIRPα) on macrophages with CD47 on cancer cells is thought to prevent antibody (Ab)-dependent cellular phagocytosis (ADCP) of the latter cells by the former. Blockade of the CD47-SIRPα interaction by Abs to CD47 or to SIRPα, in combination with tumor-targeting Abs such as rituximab, thus inhibits tumor formation by promoting macrophage-mediated ADCP of cancer cells. Here we show that monotherapy with a monoclonal Ab (mAb) to SIRPα that also recognizes SIRPβ1 inhibited tumor formation by bladder and mammary cancer cells in mice, with this inhibitory effect being largely dependent on macrophages. The mAb to SIRPα promoted polarization of tumor-infiltrating macrophages toward an antitumorigenic phenotype, resulting in the killing and phagocytosis of cancer cells by the macrophages. Ablation of SIRPα in mice did not prevent the inhibitory effect of the anti-SIRPα mAb on tumor formation or its promotion of the cancer cell–killing activity of macrophages, however. Moreover, knockdown of SIRPβ1 in macrophages attenuated the stimulatory effect of the anti-SIRPα mAb on the killing of cancer cells, whereas an mAb specific for SIRPβ1 mimicked the effect of the anti-SIRPα mAb. Our results thus suggest that monotherapy with Abs to SIRPα/SIRPβ1 induces antitumorigenic macrophages and thereby inhibits tumor growth and that SIRPβ1 is a potential target for cancer immunotherapy.Proceedings of the National Academy of Sciences, Jan. 2022, Proceedings of the National Academy of Sciences, 119(1) (1), e2109923118 - e2109923118Scientific journal
- (株)メディカルレビュー社, Sep. 2021, がん分子標的治療, 19(1) (1), 82 - 88, Japanese
- (一社)日本癌学会, Sep. 2021, 日本癌学会総会記事, 80回, [E2 - 6], English免疫系ヒト化マウスモデルによるヒトマクロファージを標的としたがん免疫療法の開発
- Cross talk between different signaling pathways is thought to be important for regulation of homeostasis of, as well as oncogenesis of, the intestinal epithelium. Expression of an active form of K-Ras specifically in intestinal epithelial cells (IECs) of mice (IEC-RasDA mice) resulted in the development of hyperplasia in the small intestine and colon of mice. IEC-RasDA mice also manifested the increased proliferation of IECs. In addition, the number of goblet cells markedly increased, while that of Paneth cells decreased in IEC-RasDA mice. Development of intestinal organoids was markedly enhanced for IEC-RasDA mice compared with control mice. Whereas, the expression of Wnt target genes was significantly reduced in the in intestinal crypts from IEC-RasDA mice compared with that apparent for the control. Our results thus suggest that K-Ras promotes the proliferation of IECs as well as generation of goblet cells. By contrast, Ras counter-regulates the Wnt signaling and thereby contribute to the proper regulation of intestinal epithelial cell homeostasis.2021, PloS one, 16(8) (8), e0256774, English, International magazineScientific journal
- The turnover of intestinal epithelial cells (IECs) is relatively rapid (3-5 days in mouse and human), and this short existence and other aspects of the homeostasis of IECs are tightly regulated by various signaling pathways including Wnt-β-catenin signaling. Dysregulation of IEC homeostasis likely contributes to the development of intestinal inflammation and intestinal cancer. The roles of receptor protein tyrosine kinases and their downstream signaling molecules such as Src family kinases, Ras, and mTOR in homeostatic regulation of IEC turnover have recently been evaluated. These signaling pathways have been found to promote not only the proliferation of IECs but also the differentiation of progenitor cells into secretory cell types such as goblet cells. Of note, signaling by Src family kinases, Ras, and mTOR has been shown to oppose the Wnt-β-catenin signaling pathway and thereby to limit the number of Lgr5+ intestinal stem cells or of Paneth cells. Such cross-talk of signaling pathways is important not only for proper regulation of IEC homeostasis but for the development of intestinal tumors and potentially for anticancer therapy.Wiley, Jan. 2021, Cancer Science, 112(1) (1), 16 - 21, English, International magazineScientific journal
- Cell signaling important for homeostatic regulation of colonic epithelial cells (CECs) remains poorly understood. Mammalian target of rapamycin complex 1 (mTORC1), a protein complex that contains the serine-threonine kinase mTOR, mediates signaling that underlies the control of cellular functions such as proliferation and autophagy by various external stimuli. We here show that ablation of tuberous sclerosis complex 2 (Tsc2), a negative regulator of mTORC1, specifically in intestinal epithelial cells of mice resulted in increased activity of mTORC1 of, as well as increased proliferative activity of, CECs. Such Tsc2 ablation also reduced the population of Lgr5-positive colonic stem cells and the expression of Wnt target genes in CECs. The stimulatory phosphorylation of the kinase Akt and inhibitory phosphorylation of glycogen synthase kinase 3β were both markedly decreased in the colon of the Tsc2 conditional knockout (CKO) mice. Development of colonic organoids with cryptlike structures was enhanced for Tsc2 CKO mice compared with control mice. Finally, Tsc2 CKO mice manifested increased susceptibility to dextran sulfate sodium-induced colitis. Our results thus suggest that mTORC1 activity promotes the proliferation of, as well as the expression of Wnt target genes in, CECs and thereby contributes to colonic organogenesis and homeostasis.Springer Science and Business Media LLC, Dec. 2020, Scientific Reports, 10(1) (1), 13810 - 13810, English, International magazineScientific journal
- The CD47-Signal regulatory protein α (SIRPα) singling axis acts as a crucial regulator that limits the phagocytic activity of professional phagocytes such as macrophages. Recent studies have demonstrated that the interaction between CD47 on tumor cells and SIRPα on macrophages is implicated in the ability of tumors to evade immunosurveillance. Targeting the CD47-SIRPα interaction is therefore considered to be a promising approach for cancer therapy. Herein, we review some of studies displaying the potential clinical application of antibodies and other modalities that target the CD47-SIRPα interaction. Current limitations of the CD47-SIRPα-targeted immunotherapeutic approaches are also discussed as well as other avenues for future study to improve the current strategies in targeting the CD47-SIRPα signaling axis for cancer immunotherapy.Lead, Informa UK Limited, Oct. 2020, Expert Opinion on Therapeutic Targets, 24(10) (10), 945 - 951, English, International magazineScientific journal
- (一社)日本癌学会, Oct. 2020, 日本癌学会総会記事, 79回, OE2 - 4, English免疫系ヒト化マウスモデルによるヒトマクロファージを標的としたがん免疫療法の開発
- Signal regulatory protein α (SIRPα) is expressed predominantly on type 2 conventional dendritic cells (cDC2s) and macrophages. We previously showed that mice systemically lacking SIRPα were resistant to experimental autoimmune encephalomyelitis (EAE). Here, we showed that deletion of SIRPα in CD11c+ cells of mice (SirpaΔDC mice) also markedly ameliorated the development of EAE. The frequency of cDCs and migratory DCs (mDCs), as well as that of Th17 cells, were significantly reduced in draining lymph nodes of SirpaΔDC mice at the onset of EAE. In addition, we found the marked reduction in the number of Th17 cells and DCs in the CNS of SirpaΔDC mice at the peak of EAE. Whereas inducible systemic ablation of SIRPα before the induction of EAE prevented disease development, that after EAE onset did not ameliorate the clinical signs of disease. We also found that EAE development was partially attenuated in mice with CD11c+ cell-specific ablation of CD47, a ligand of SIRPα. Collectively, our results suggest that SIRPα expressed on CD11c+ cells, such as cDC2s and mDCs, is indispensable for the development of EAE, being required for the priming of self-reactive Th17 cells in the periphery as well as for the inflammation in the CNS.Wiley, Oct. 2020, European Journal of Immunology, 50(10) (10), 1560 - 1570, English, International magazineScientific journal
- Medium-sized macrocyclic peptides are an alternative to small compounds and large biomolecules as a class of pharmaceutics. The CD47-SIRPα signaling axis functions as an innate immune checkpoint that inhibits phagocytosis in phagocytes and has been implicated as a promising target for cancer immunotherapy. The potential of macrocyclic peptides that target this signaling axis as immunotherapeutic agents has remained unknown, however. Here we have developed a macrocyclic peptide consisting of 15 amino acids that binds to the ectodomain of mouse SIRPα and efficiently blocks its interaction with CD47 in an allosteric manner. The peptide markedly promoted the phagocytosis of antibody-opsonized tumor cells by macrophages in vitro as well as enhanced the inhibitory effect of anti-CD20 or anti-gp75 antibodies on tumor formation or metastasis in vivo. Our results suggest that allosteric inhibition of the CD47-SIRPα interaction by macrocyclic peptides is a potential approach to cancer immunotherapy.Corresponding, Elsevier BV, Sep. 2020, Cell Chemical Biology, 27(9) (9), 1181 - 1191.e7, English, International magazineScientific journal
- Nonhematopoietic stromal cells contribute to the organization and homeostasis of secondary lymphoid organs by producing cytokines and chemokines. The development and maintenance of these stromal cells are thought to be regulated by innate immune cells. Indeed, we recently showed that signal regulatory protein α (SIRPα)-positive dendritic cells (DCs) are essential for the proliferation and survival of podoplanin (Pdpn)-positive fibroblastic reticular cells (FRCs) in mouse spleen. We have now established an in vitro culture system for lymph node stromal cells (LNSCs) isolated from mouse peripheral LNs. Activated DCs and TNF-α each promoted the proliferation of cultured LNSCs, most of which were found to be Pdpn+ FRCs. Furthermore, ablation of SIRPα in CD11c+ cells attenuated this effect of DCs on LNSC proliferation. Transplantation of activated DCs together with cultured LNSCs into the renal subcapsular space markedly increased the number of ER-TR7+ stromal cells as well as induced the accumulation of T cells and increased the expression of Ccl19 in the transplants. Ablation of SIRPα in CD11c+ cells greatly impaired the development of LN-like structure in the transplants. Our findings thus suggest that SIRPα+ DCs are important for the proliferation and differentiation of Pdpn+ FRCs in peripheral LNs.Wiley, Sep. 2019, European Journal of Immunology, 49(9) (9), 1364 - 1371, English, International magazine[Refereed]Scientific journal
- Regulation of Small Intestinal Epithelial Homeostasis by Tsc2-mTORC1 Signaling.Mammalian target of rapamycin complex 1 (mTORC1), a protein complex containing the serine/threonine kinase mTOR, integrates various growth stimulating signals. mTORC1 is expressed in intestinal epithelial cells (IECs), whereas the physiological roles of this protein complex in homeostasis of IECs remain virtually unknown. We here generated mice, in which tuberous sclerosis complex 2 (Tsc2), a negative regulator of mTORC1, was specifically ablated in IECs (Tsc2 CKO mice). Ablation of Tsc2 enhanced the phosphorylation of mTORC1 downstream molecules such as ribosomal S6 protein and 4E-BP1 in IECs. Tsc2 CKO mice manifested the enhanced proliferative activity of IECs in intestinal crypts as well as the promoted migration of these cells along the crypt-villus axis. The mutant mice also manifested the increased apoptotic rate of IECs as well as the increased ectopic Paneth cells, which are one of the major differentiated IECs. In addition, in vitro study showed that ablation of Tsc2 promoted the development of intestinal organoids without epidermal growth factor, while mTORC1 inhibitor, rapamycin, diminished this phenotype. Our results thus suggest that Tsc2-mTORC1 signaling regulates the proliferation, migration, and positioning of IECs, and thereby contributes to the proper regulation of intestinal homeostasis.Apr. 2019, The Kobe journal of medical sciences, 64(6) (6), E200-E209 - E209, English, Domestic magazine[Refereed]Scientific journal
- Intestinal epithelial cells (IECs) are regenerated continuously from intestinal stem cells (ISCs) near the base of intestinal crypts in order to maintain homeostasis and structural integrity of intestinal epithelium. Epidermal growth factor (EGF) is thought to be important to drive the proliferation and differentiation of IECs from ISCs, it remains unknown whether other growth factors or lipid mediators are also important for such regulation, however. Here we show that lysophosphatidic acid (LPA), instead of EGF, robustly promoted the development of intestinal organoids prepared from the mouse small intestine. Indeed, LPA exhibited the proliferative activity of IECs as well as induction of differentiation of IECs into goblet cells, Paneth cells, and enteroendocrine cells in intestinal organoids. Inhibitors for LPA receptor 1 markedly suppressed the LPA-promoted development of intestinal organoids. LPA also promoted the phosphorylation of extracellular signal-regulated kinase (ERK) 1/2 in intestinal organoids, whereas inhibition of mitogen-activated protein kinase/ERK kinase (MEK) 1/2 significantly suppressed the development of, as well as the proliferative activity and differentiation of, intestinal organoids in response to LPA. Our results thus suggest that LPA is a key factor that drives the proliferation and differentiation of IECs.Apr. 2019, PloS one, 14(4) (4), e0215255, English, International magazine[Refereed]Scientific journal
- A characteristic subset of microglia expressing CD11c appears in response to brain damage. However, the functional role of CD11c+ microglia, as well as the mechanism of its induction, are poorly understood. Here we report that the genetic ablation of signal regulatory protein α (SIRPα), a membrane protein, induced the emergence of CD11c+ microglia in the brain white matter. Mice lacking CD47, a physiological ligand of SIRPα, and microglia-specific SIRPα-knockout mice exhibited the same phenotype, suggesting that an interaction between microglial SIRPα and CD47 on neighbouring cells suppressed the emergence of CD11c+ microglia. A lack of SIRPα did not cause detectable damage to the white matter, but resulted in the increased expression of genes whose expression is characteristic of the repair phase after demyelination. In addition, cuprizone-induced demyelination was alleviated by the microglia-specific ablation of SIRPα. Thus, microglial SIRPα suppresses the induction of CD11c+ microglia that have the potential to accelerate the repair of damaged white matter.Mar. 2019, eLife, 8(. pii) (. pii), e42025, English, International magazine[Refereed]Scientific journal
- Intestinal epithelial cells (IECs) play a pivotal role in the maintenance of the integrity and barrier function of the intestinal epithelium. Dysfunctions of IECs are thought to participate in the disruption of the intestinal epithelial barrier, resulting in gastrointestinal diseases, such as colitis and colorectal cancer. Here we show that IEC-specific COOH-terminal Src kinase (Csk)-deficient mice (Csk CKO mice) manifested the increased susceptibility to dextran sodium sulfate (DSS)-induced colitis, a model of inflammatory bowel disease. DSS-treated Csk CKO mice also exhibited the significantly elevated intestinal permeability. Following DSS treatment, Csk CKO mice exhibited the higher proliferative activity of colonic epithelial cells and the increased number of apoptotic cells in the colon compared with that apparent for control mice. Moreover, the abundance of the tight junction protein occludin, which regulates cell-cell adhesion as well as epithelial permeability, was markedly reduced in the colon of DSS-treated Csk CKO mice. These results thus suggest that Csk in IECs plays important roles in the regulation of the intestinal epithelial barrier function and protection against colitis.Sep. 2018, Biochem Biophys Res Commun, 504(1) (1), 109 - 114, English, International magazine[Refereed]Scientific journal
- Blackwell Publishing Ltd, May 2018, Cancer Science, 109(5) (5), 1300 - 1308, English[Refereed]Scientific journal
- In the mouse olfactory bulb (OB), interneurons such as granule cells and periglomerular cells are continuously replaced by adult-born neurons, which are generated in the subventricular zone (SVZ) of the brain. We have now investigated the role of commensal bacteria in regulation of such neuronal cell turnover in the adult mouse brain. Administration of mixture of antibiotics to specific pathogen-free (SPF) mice markedly attenuated the incorporation of bromodeoxyuridine (BrdU) into the SVZ cells. The treatment with antibiotics also reduced newly generated BrdU-positive neurons in the mouse OB. In addition, the incorporation of BrdU into the SVZ cells of germ-free (GF) mice was markedly reduced compared to that apparent for SPF mice. In contrast, the reduced incorporation of BrdU into the SVZ cells of GF mice was recovered by their co-housing with SPF mice, suggesting that commensal bacteria promote the incorporation of BrdU into the SVZ cells. Finally, we found that administration of ampicillin markedly attenuated the incorporation of BrdU into the SVZ cells of SPF mice. Our results thus suggest that ampicillin-sensitive commensal bacteria regulate the neurogenesis in the SVZ of adult mouse brain.Apr. 2018, Biochemical and biophysical research communications, 498(4) (4), 824 - 829, English, International magazine[Refereed]Scientific journal
- Nov. 2017, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 114(47) (47), E10151 - E10160, English[Refereed]Scientific journal
- Sep. 2017, JOURNAL OF PHARMACEUTICAL SCIENCES, 106(9) (9), 2904 - 2908, English[Refereed]Scientific journal
- Signal regulatory protein α (SIRPα), is an immunoglobulin superfamily protein that is predominantly expressed in macrophages and dendritic cells (DCs), especially CD4+ conventional DCs (cDCs). In this study, we demonstrated that, in addition to the reduced number of CD4+ cDCs, the number of T cells was significantly decreased in the spleen of Sirpa–/– mice, in which full-length神戸大学医学部, Aug. 2017, The Kobe journal of the medical sciences, 63(1) (1), 22 - 29, English[Refereed]Scientific journal
- Role of SIRPα in Homeostatic Regulation of T Cells and Fibroblastic Reticular Cells in the SpleenSignal regulatory protein α (SIRPα), is an immunoglobulin superfamily protein that is predominantly expressed in macrophages and dendritic cells (DCs), especially CD4+ conventional DCs (cDCs). In this study, we demonstrated that, in addition to the reduced number of CD4+ cDCs, the number of T cells was significantly decreased in the spleen of Sirpa-/- mice, in which full-length of SIRPα protein was systemically ablated. The size of the T cell zone was markedly reduced in the spleen of Sirpa-/- mice. In addition, Sirpa-/- mice revealed a marked reduction of CCL19, CCL21, and IL-7 expression, which are thought to be important for homeostasis of T cells in the spleen. Consistently, the abundance of fibroblastic reticular cells (FRCs), a subset of stromal cells in the T cell zone, was markedly reduced in the spleen of Sirpa-/- mice compared with Sirpaf/f mice. Moreover, we demonstrated that the mRNA expression of Lymphotoxin (LT) α, LTβ, and LIGHT was significantly reduced in the spleen of Sirpa-/- mice. These data thus suggest that SIRPα is essential for steady-state homeostasis of T cells and FRCs in the spleen.Aug. 2017, Kobe J Med Sci, 63(1) (1), E22 - E29, English, Domestic magazine[Refereed]Scientific journal
- Tumor cells are thought to evade immune surveillance through interaction with immune cells. Much recent attention has focused on the modification of immune responses as a basis for new cancer treatments. SIRPα is an Ig superfamily protein that inhibits phagocytosis in macrophages upon interaction with its ligand CD47 expressed on the surface of target cells. Here, we show that SIRPα is highly expressed in human renal cell carcinoma and melanoma. Furthermore, an anti-SIRPα Ab that blocks the interaction with CD47 markedly suppressed tumor formation by renal cell carcinoma or melanoma cells in immunocompetent syngeneic mice. This inhibitory effect of the Ab appeared to be mediated by dual mechanisms: direct induction of Ab-dependent cellular phagocytosis of tumor cells by macrophages and blockade of CD47-SIRPα signaling that negatively regulates such phagocytosis. The antitumor effect of the Ab was greatly attenuated by selective depletion not only of macrophages but also of NK cells or CD8+ T cells. In addition, the anti-SIRPα Ab also enhances the inhibitory effects of Abs against CD20 and programmed cell death 1 (PD-1) on tumor formation in mice injected with SIRPα-nonexpressing tumor cells. Anti-SIRPα Abs thus warrant further study as a potential new therapy for a broad range of cancers.Jan. 2017, JCI Insight, 2(1) (1), e89140, English, International magazine[Refereed]Scientific journal
- Nov. 2016, MOLECULAR AND CELLULAR BIOLOGY, 36(22) (22), 2811 - 2823, English[Refereed]Scientific journal
- May 2016, PLOS ONE, 11(5) (5), e0156334, English[Refereed]Scientific journal
- Aug. 2015, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 112(31) (31), E4264 - E4271, English[Refereed]Scientific journal
- Jul. 2015, GENES TO CELLS, 20(7) (7), 578 - 589, English[Refereed]Scientific journal
- Jun. 2015, Genes Cells, 20(6) (6), 451 - 463, English[Refereed]Scientific journal
- Blackwell Publishing Ltd, Jun. 2015, Genes to Cells, 20(6) (6), 451 - 463, English[Refereed]Scientific journal
- May 2015, MOLECULAR AND CELLULAR BIOLOGY, 35(9) (9), 1557 - 1572, English[Refereed]Scientific journal
- Jun. 2014, JOURNAL OF BIOCHEMISTRY, 155(6) (6), 335 - 344, English[Refereed]Scientific journal
- Mar. 2014, JOURNAL OF BIOLOGICAL CHEMISTRY, 289(10) (10), 6451 - 6461, English[Refereed]Scientific journal
- Mar. 2014, PLOS ONE, 9(3) (3), e92904, English[Refereed]Scientific journal
- Jan. 2014, METHODS, 65(2) (2), 254 - 259, English[Refereed]Scientific journal
- Tyrosine Phosphorylation of Carcinoembryonic Antigen-related Cell Adhesion Molecule 20 and Its Functional Role.Carcinoembryonic antigen-related cell adhesion molecule (CEACAM) 20 is an immunoglobulin-superfamily transmembrane protein that contains an immunoreceptor tyrosine-based activation motif (ITAM) in its cytoplasmic region. However, the mechanism for tyrosine phosphorylation of, or the physiological function of, this protein remains largely unknown. Here we have shown that CEACAM20 is indeed tyrosine-phosphorylated by either treatment with pervanadate or forced expression of c-Src. In addition, Tyr522, Tyr559 or Tyr570, the latter two of which are within the ITAM, is likely important for such tyrosine phosphorylation. Forced expression of Myc-tagged wild-type CEACAM20 promoted the phagocytic activity of cultured cells for microbeads coupled with anti-Myc antibodies. By contrast, such phagocytic activity was markedly reduced when a mutant form of CEACAM20, in which Tyr559 and Tyr570 were substituted with phenylalanine, was expressed. Furthermore, the CEACAM20-mediated phagocytic activity was markedly prevented by the treatment with an inhibitor for either Src family kinases (SFKs), Syk, phosphoinositide 3-kinase (PI3K) or phospholipase C-γ (PLCγ). Inhibition of actin polymerization by Cytochalasin D significantly inhibited the CEACAM20-mediated phagocytosis. These results thus suggest that tyrosine phosphorylation of CEACAM20 likely promotes phagocytic activity of the cells. The CEACAM20-mediated phagocytic activity requires the activation of SFKs, Syk, PI3K or PLCγ.Mar. 2013, The Kobe journal of medical sciences, 59(5) (5), E172-E183, English, Domestic magazineScientific journal
- Nov. 2012, BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 428(4) (4), 475 - 481, English[Refereed]Scientific journal
- Jun. 2012, JOURNAL OF NEUROCHEMISTRY, 121(6) (6), 891 - 902, English[Refereed]Scientific journal
- Jun. 2012, JOURNAL OF IMMUNOLOGY, 188(11) (11), 5397 - 5407, English[Refereed]Scientific journal
- Jul. 2011, JOURNAL OF IMMUNOLOGY, 187(1) (1), 291 - 297, English[Refereed]Scientific journal
- Mar. 2011, IMMUNOLOGY LETTERS, 135(1-2) (1-2), 100 - 107, English[Refereed]Scientific journal
- Dec. 2010, GENES TO CELLS, 15(12) (12), 1189 - 1200, English[Refereed]Scientific journal
- Nov. 2010, BLOOD, 116(18) (18), 3517 - 3525, English[Refereed]Scientific journal
- Oct. 2010, BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 401(3) (3), 385 - 389, English[Refereed]Scientific journal
- Aug. 2010, JOURNAL OF NEUROSCIENCE, 30(31) (31), 10472 - 10483, English[Refereed]Scientific journal
- Jul. 2010, JOURNAL OF CELLULAR PHYSIOLOGY, 224(1) (1), 195 - 204, English[Refereed]Scientific journal
- May 2010, GENES TO CELLS, 15(5) (5), 513 - 524, English[Refereed]Scientific journal
- Jan. 2010, JOURNAL OF COMPARATIVE NEUROLOGY, 518(2) (2), 119 - 136, English[Refereed]Scientific journal
- Oct. 2009, CANCER SCIENCE, 100(10) (10), 1786 - 1793, English[Refereed]Scientific journal
- Mar. 2009, GENES TO CELLS, 14(3) (3), 295 - 308, English[Refereed]Scientific journal
- Feb. 2009, TRENDS IN CELL BIOLOGY, 19(2) (2), 72 - 80, English[Refereed]Scientific journal
- Nov. 2008, ENDOCRINOLOGY, 149(11) (11), 5662 - 5669, English[Refereed]Scientific journal
- Nov. 2008, IMMUNOLOGY LETTERS, 121(1) (1), 52 - 60, English[Refereed]Scientific journal
- Jul. 2008, BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 371(3) (3), 561 - 566, English[Refereed]Scientific journal
- May 2008, Kitakanto Medical Journal, 58(2) (2), 133 - 139, English[Refereed]Scientific journal
- Apr. 2008, JOURNAL OF CELL SCIENCE, 121(8) (8), 1213 - 1223, English[Refereed]Scientific journal
- Feb. 2008, GENES TO CELLS, 13(2) (2), 209 - 219, English[Refereed]Scientific journal
- (一社)日本臨床免疫学会, Aug. 2007, 日本臨床免疫学会会誌, 30(4) (4), 312 - 312, Japanese
- Jul. 2007, JOURNAL OF IMMUNOLOGY, 179(2) (2), 869 - 877, English[Refereed]Scientific journal
- May 2007, JOURNAL OF IMMUNOLOGY, 178(10) (10), 6164 - 6172, English[Refereed]Scientific journal
- Nov. 2006, JOURNAL OF NEUROSCIENCE, 26(48) (48), 12397 - 12407, English[Refereed]Scientific journal
- Sep. 2006, CANCER SCIENCE, 97(9) (9), 889 - 895, English[Refereed]Scientific journal
- Sep. 2006, JOURNAL OF IMMUNOLOGY, 177(5) (5), 3123 - 3132, English[Refereed]Scientific journal
- May 2006, BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 343(4) (4), 1197 - 1200, English[Refereed]Scientific journal
- 2006, 実験医学, 第24巻(第13号) (第13号), 1951 - 1959, JapaneseSHPチロシンホスファターゼによる細胞運動・細胞接着制御[Refereed]Scientific journal
- 日本癌学会, Sep. 2019, 日本癌学会総会記事, 78回, P - 2169, EnglishCD47-SIRPαシグナル系を標的としたマクロファージによるがん細胞排除を促進する新規大環状ペプチドの開発(A novel macrocyclic peptide targets the CD47-SIRPalpha axis and enhances the macrophage-mediated tumor killing)
- 30 Sep. 2018, 臨床血液, 59(9) (9), 1687, EnglishSIRPα+ dendritic cells regulate homeostasis of fibroblastic reticular cells in the adult spleen
- (公社)日本生化学会, Sep. 2018, 日本生化学会大会(Web), 91回, [2T13m - 325)], Japanese常在細菌による成体マウス脳室下帯におけるニューロン新生の制御
- Tumor cells evade immune surveillance through direct or indirect interactions with various types of immune cell, with much recent attention being focused on modifying immune cell responses as the basis for the development of new cancer treatments. Signal regulatory protein α (SIRPα) and CD47 are both transmembrane proteins that interact with each other and constitute a cell-cell communication system. SIRPα is particularly abundant in myeloid cells such as macrophages and dendritic cells, whereas CD47 is expressed ubiquitously and its expression level is elevated in cancer cells. Recent studies have shown that blockade of CD47-SIRPα interaction enhances the phagocytic activity of phagocytes such as macrophages toward tumor cells in vitro as well as resulting in the efficient eradication of tumor cells in a variety of xenograft or syngeneic mouse models of cancer. Moreover, CD47 blockade has been shown to promote the stimulation of tumor-specific cytotoxic T cells by macrophages or dendritic cells. Biological agents, such as Abs and recombinant proteins, that target human CD47 or SIRPα have been developed and are being tested in preclinical models of human cancer or in clinical trials with cancer patients. Preclinical studies have also suggested that CD47 or SIRPα blockade may have a synergistic antitumor effect in combination with immune checkpoint inhibitors that target the adaptive immune system. Targeting of the CD47-SIRPα signaling system is thus a promising strategy for cancer treatment based on modulation of both innate and acquired immune responses to tumor cells.Aug. 2018, Cancer science, 109(8) (8), 2349 - 2357, English, International magazine[Refereed]
- 2018, 日本癌学会学術総会抄録集(Web), 77th, ROMBUNNO.P‐3042 (WEB ONLY), EnglishRole of intestinal epithelial Src family kinases in the control of intestinal inflammation
- 2018, 日本癌学会学術総会抄録集(Web), 77th, ROMBUNNO.P‐1102 (WEB ONLY), EnglishRegulation of small intestinal homeostasis by Tsc2‐mTORC1 signaling
- 2018, 日本生化学会大会(Web), 91st, ROMBUNNO.1P‐297 (WEB ONLY), EnglishSrcファミリーキナーゼの炎症性腸疾患における重要性
- 2018, 日本生化学会大会(Web), 91st, ROMBUNNO.1S03e‐02 (WEB ONLY), Japanese腸上皮細胞の恒常生維持に関わるチロシンリン酸化シグナルの意義
- Jan. 2018, がん分子標的治療, 15(4) (4), 414 - 419, JapaneseCD47/SIRPαシグナルを標的としたがん免疫療法Introduction scientific journal
- Dec. 2017, CYTOKINE, 100, 55 - 55, EnglishSIRP alpha(+) dendritic cells regulate homeostasis of fibroblastic reticular cells via TNF receptor ligands in the adult spleenSummary international conference
- 2017, 日本生化学会大会(Web), 90th, ROMBUNNO.2P‐0458 (WEB ONLY), English腸上皮の恒常性制御におけるTsc2‐mTORC1シグナルの役割
- 2017, 日本癌学会学術総会抄録集(Web), 76th, ROMBUNNO.S5‐3 (WEB ONLY), EnglishAnti‐SIRPα antibodies provide a basis for new approaches to cancer immunotherapy
- 2017, 日本癌学会学術総会抄録集(Web), 76th, ROMBUNNO.J‐1040 (WEB ONLY), EnglishEstablishment of a potential new PDX mouse model for personalized cancer immunotherapy
- 2017, 日本癌学会学術総会抄録集(Web), 76th, ROMBUNNO.E‐1007 (WEB ONLY), EnglishRegulation of intestinal epithelial homeostasis by Src family kinases through Rac and YAP
- 2017, 日本癌学会学術総会抄録集(Web), 76th, ROMBUNNO.P‐3032 (WEB ONLY), EnglishRole of Tsc2‐mTORC1 signaling in intestinal homeostasis
- 2017, 日本生化学会大会(Web), 90th, ROMBUNNO.3AT26‐02(3P‐0901) (WEB ONLY), Japaneseがん‐マクロファージ間相互作用を標的とした新規がん免疫療法の開発
- Dec. 2016, Expert Review of Gastroenterology & Hepatology, 10(12) (12), 1313 - 1315, English[Refereed]Others
- (公社)日本生化学会, Sep. 2016, 日本生化学会大会プログラム・講演要旨集, 89回, [2P - 238], Japanese短鎖脂肪酸は腸上皮細胞のターンオーバーを調節する(Short chain fatty acids regulate the turnover of intestinal epithelial cells)
- 2016, 日本癌学会学術総会抄録集(Web), 75th, ROMBUNNO.J‐1004 (WEB ONLY), EnglishThe anti‐SIRPα antibody prevents tumor formation: a novel strategy for cancer therapy
- 2016, 日本生物学的精神医学会(Web), 38th, 154 (WEB ONLY), EnglishSIRPα欠損マウスはLPS投与によって誘導される低体温症が重症化する
- 2016, 北関東医学会総会プログラム・抄録, 63rd, 27‐28, JapaneseSIRPα欠損マウスにおけるクプリゾン感受性の亢進
- 2016, 日本生化学会大会(Web), 89th, ROMBUNNO.1S10‐6 (WEB ONLY), Japanese細胞間シグナルCD47‐SIRPα系の生理機能とその臨床応用
- 2016, 日本生物学的精神医学会(Web), 38th, 149 (WEB ONLY), Japanese白質におけるミクログリア恒常性制御
- Oct. 2015, 生体の科学, 66(5号) (5号), 432 - 433, Japanese[Invited]Introduction commerce magazine
- 日本生化学会, Oct. 2015, 生化学, 87(5号) (5号), 547 - 553, Japanese[Invited]Introduction scientific journal
- 北関東医学会, 01 Aug. 2015, 北関東医学会総会プログラム・抄録, 62nd(3) (3), 20 - 21, JapaneseミクログリアにおけるSIRPαシグナルの役割
- 05 Jun. 2015, 日本細胞生物学会大会要旨集, 67th, 175, Japanese腸粘膜上皮細胞の微絨毛に局在する受容体型チロシンホスファターゼSAP‐1とCEACAM20による腸管免疫制御
- 05 Jun. 2015, 日本細胞生物学会大会要旨集, 67th, 199, Japanese腸内細菌による腸上皮細胞の寿命制御
- 2015, 日本癌学会学術総会抄録集(Web), 74th, J‐1203 (WEB ONLY), EnglishImportance of commensal bacteria and short‐chain fatty acids for the growth and migration of intestinal epithelial cells
- 2015, 日本神経化学会大会抄録集(Web), 58th, ROMBUNNO.2P‐34 (WEB ONLY), EnglishCell‐cell interactions via CD47‐SIRPα signal regulate microglial activation
- 2015, 日本生化学会大会(Web), 88th, 3P0174 (WEB ONLY), English腸上皮細胞の増殖・移動制御における腸内細菌と短鎖脂肪酸の重要性
- 2015, 日本生化学会大会(Web), 88th, 2T21P-14(2P0206) (WEB ONLY), English腸上皮組織の恒常性制御におけるCskとSrcファミリーキナーゼの役割
- 2015, 日本癌学会学術総会抄録集(Web), 74th, J‐1283 (WEB ONLY), EnglishRole of C‐terminal Src kinase (Csk) and Src family kinases in homeostasis of the intestinal epithelium
- 18 Nov. 2014, 日本免疫学会総会・学術集会記録, 43(Proceedings) (Proceedings), 38, EnglishEssential role of SIRP α on dendritic cells in organization and homeostasis of the spleen
- 2014, 日本分子生物学会年会プログラム・要旨集(Web), 37th, 2W9-3(2P-0718) (WEB ONLY), Japanese細胞間コミュニケーションシステムCD47‐SIRPα系による血液・免疫系の制御
- 北関東医学会, 01 Aug. 2013, The Kitakanto medical journal = 北関東医学, 63(3) (3), 321 - 322, Japanese細胞質型チロシンホスファターゼShp2の成熟脳における機能解析
- 北関東医学会, 01 Aug. 2013, 北関東医学会総会プログラム・抄録, 60th(3) (3), 24 - 25, JapaneseSIRPαによる脾臓T細胞の恒常性の調節
- Oct. 2012, JOURNAL OF NEUROCHEMISTRY, 123, 67 - 67, EnglishHypothermia-induced tyrosine phosphorylation of SIRP alpha in the brainSummary international conference
- Jun. 2012, ANNALS OF THE RHEUMATIC DISEASES, 71, 73 - 73, EnglishIMPORTANCE OF THE PROTEIN TYROSINE PHOSPHATASE SHP1 IN DENDRITIC CELLS FOR PREVENTION OF TH1 CELL DIFFERENTIATION AND AUTOIMMUNITY: A POTENTIAL TARGET FOR THE THERAPYSummary international conference
- 2012, 日本生化学会大会(Web), 85th, 3T29-06 (WEB ONLY), Japanese脾臓T細胞の恒常性調節へのSIRPαの関与
- Dec. 2011, TRENDS IN NEUROSCIENCES, 34(12) (12), 629 - 637, English[Refereed]Book review
- 07 Nov. 2011, 日本免疫学会総会・学術集会記録, 40, 199, EnglishDendritic cell‐specific depletion of protein tyrosine phosphatase Shp1 promotes Th1 differentiation causes autoimmunit
- 学研メディカル秀潤社, 2011, 細胞工学, 30(6) (6), 586 - 589, Japanese特集を読むまえに 基礎の基礎 (特集 ホスファターゼ研究新章--創薬につながる新機能と第四の脱リン酸化酵素の発見)
- Dec. 2010, CELLULAR SIGNALLING, 22(12) (12), 1811 - 1817, English[Refereed]Book review
- 01 Aug. 2010, Kitakanto Medical Journal, 60(3) (3), 302 - 303, Japanese脳におけるSIRPαチロシンリン酸化の解析
- 2010, NEUROSCIENCE RESEARCH, 68, E58 - E58, EnglishSummary international conference
- 2010, 生化学, ROMBUNNO.4T9-2, Japanese血管内皮細胞のシェアストレス刺激応答におけるVE‐PTPの機能解析
- 2010, 生化学, ROMBUNNO.4P-0447, Japanese腸微絨毛特異的な発現を示す受容体型チロシンホスファターゼSAP‐1とIL‐10による炎症性腸疾患の制御
- 2010, 生化学, ROMBUNNO.4P-0434, Japanese低温ストレスによるSIRPαチロシンリン酸化の誘導
- 科学評論社, Nov. 2009, Clinical immunology & allergology, 52(5) (5), 494 - 498, JapaneseRegulation of the functions of dendritic cells by SIRPα
- 30 Sep. 2009, 臨床血液, 50(9) (9), 907, EnglishEssential roles of the CD47‐SIRP α signaling in homeostasis of lymphoid tissue dendritic cells
- 25 Sep. 2009, 生化学, ROMBUNNO.4T5A-16, Japanese腸微絨毛特異的な発現を示す受容体型チロシンホスファターゼSAP‐1とIL‐10による炎症性腸疾患の制御
- 25 Sep. 2009, 生化学, ROMBUNNO.4T5A-18, JapaneseVE‐PTPによるRas,インテグリン依存的なラメリポディア形成の促進
- 31 Aug. 2009, 日本癌学会学術総会記事, 68th, 246, EnglishPromotion by VE‐PTP of lamellipodium formation in cooperation with Ras and integrin
- 31 Aug. 2009, 日本癌学会学術総会記事, 68th, 204, EnglishTyrosine phosphorylation of SAP‐1, a receptor‐type protein tyrosine phosphatase, and its association with Grb2
- 北関東医学会, 01 Aug. 2009, The Kitakanto medical journal, 59(3) (3), 322 - 322, Japanese2. 脳におけるSHPS-1シグナルの解析(第56回北関東医学会総会抄録 一般演題)
- 20 Apr. 2009, 日本内分泌学会雑誌, 85(1) (1), 305, Japanese受容体型膜蛋白質SHPS‐1のインスリン分泌制御における機能解析
- 科学評論社, Mar. 2009, Clinical immunology & allergology, 51(3) (3), 232 - 241, JapaneseRegulation of TLR signaling by phosphatases and their binding proteins
- 2009, 北関東医学会総会プログラム・抄録, 56th, 14, Japanese脳におけるSHPS‐1シグナルの解析
- 2009, 神経組織の成長・再生・移植研究会学術集会プログラム・予稿集, 24th, 64, Japanese神経系における受容体型膜蛋白質SHPS‐1の機能解析
- 05 Nov. 2008, 日本免疫学会総会・学術集会記録, 38, 203, EnglishEssential roles of SHPS‐1 in homeostasis of dendritic cells
- 05 Nov. 2008, 日本免疫学会総会・学術集会記録, 38, 208, EnglishExpression of SHPS‐1 in the intestines and regulation by SHPS‐1 of the intestinal immunity
- 15 Sep. 2008, 実験医学, 26(15) (15), 2424 - 2431, Japaneseシグナル伝達研究 II:現象から因子へ 6.CD47‐SHPS‐1系による樹状細胞の機能制御
- 北関東医学会, 01 Aug. 2008, The KITAKANTO medical journal, 58(3) (3)15.SHPS-1による樹状細胞の機能制御(一般演題,第55回北関東医学会総会抄録)
- 科学評論社, Jun. 2008, Clinical immunology & allergology, 49(6) (6), 713 - 722, JapaneseAntitumor activity of NKT cells
- 25 Apr. 2008, 糖尿病, 51(Supplement 1) (Supplement 1), S.123, Japanese受容体型膜蛋白質SHPS‐1のインスリン分泌制御における機能解析
- 25 Oct. 2007, 日本免疫学会総会・学術集会記録, 37, 134, EnglishResistance to collagen‐induced arthritis in SHPS‐1 mutant mice
- 25 Oct. 2007, 日本免疫学会総会・学術集会記録, 37, 125, EnglishAn essential role of SHPS‐1 in proper development of dendritic cells for induction of Th17‐mediated autoimmune diseases
- 北関東医学会, 01 Aug. 2007, The KITAKANTO medical journal, 57(3) (3)14. CD47-SHPS-1系におけるトランスエンドサイトーシスの役割(一般演題,第54回北関東医学会総会抄録)
- 自己免疫性関節炎におけるSHPS-1の機能解析<B>【目的】</B>SHPS-1は単球系細胞に発現が認められる膜蛋白であるが、我々は最近、SHPS-1がマウスにおける実験的脳脊髄炎や接触性皮膚炎などの自己免疫性疾患の発症に必須であることを明らかにしている。そこで、今回我々は、関節リウマチのマウスモデルであるコラーゲン誘導関節炎(CIA)発症におけるSHPS-1の関与について検討した。<BR><B>【方法と結果】</B>SHPS-1の機能に重要である細胞内領域を特異的に欠失した変異SHPS-1を発現するマウス(MTマウス)をすでに作成しているので、これを用いてニワトリ由来のタイプIIコラーゲンで誘導されるCIAの発症を検討した。野生型マウスでは指、手関節を中心に累積発症率52%の割合で発症し、発症スコアーは3.0であった。一方、MTマウスでは全く発症が認められず、組織学的な解析においてもMTマウスの関節組織はほぼ正常に保たれていた。さらに、コラーゲンによって関節炎を誘導されたマウスにおける免疫応答を検討したところ、MTマウスではコラーゲン特異的な抗体産生能やT細胞の増殖能が減弱しており、炎症性サイトカインの産生低下も認められた。<BR><B>【考察】</B>MTマウスではCIAの発症が認められなかったことより、SHPS-1は抗原特異的免疫応答において重要なシグナル分子であり、リウマチ性疾患の治療を考える上で有力な標的となり得る事が示唆された。日本臨床免疫学会, 2007, 日本臨床免疫学会総会抄録集, 35(0) (0), 79 - 79, Japanese
- Aug. 2006, REGULATORY PEPTIDES, 135(3) (3), 158 - 159, EnglishRegulation by CD47 of epithelial cell spreading and migration and its signal transductionSummary international conference
■ Lectures, oral presentations, etc.
- 14th International Conference on Protein Phosphatase, Dec. 2020Antibodies to SIRPα/SIRPβ as a potential tool for immunotherapy of bladder cancerPoster presentation
- 14th International Conference on Protein Phosphatase, Dec. 2020Blockade of the CD47-SIRPα interaction by SIRPα-binding macrocyclic peptides as a potential cancer immunotherapyOral presentation
- 14th International Conference on Protein Phosphatase, Dec. 2020Roles of Shp2-Ras, Src family kinases, and mTOR signaling in intestinal epithelial homeostasisOral presentation
- 14th International Conference on Protein Phosphatase, Dec. 2020Role of CD47 on the regulation of peripheral T cell survival by dendritic cellsPoster presentation
- 14th International Conference on Protein Phosphatase, Dec. 2020A novel humanized mouse model for assessing human macrophage-targeted cancer immunotherapy in vivoPoster presentation
- 第79回日本癌学会学術総会ランゲルハンス細胞組織球症に対する新規治療標的分子SIRPαOral presentation
- 第79回日本癌学会学術総会腸上皮細胞の増殖・分化制御におけるK-Ras活性の役割Oral presentation
- 第79回日本癌学会学術総会膜型分子SIRPα/SIRPβ特異抗体を用いた膀胱がんに対する新規抗体療法Oral presentation
- 第79回日本癌学会学術総会Humanized mouse models for in vivo evaluation of cancer immunotherapy targeting human macrophagesOral presentation
- 第19回生体機能研究会, Sep. 2020膜型分子CD47を介した成熟T細胞の寿命制御Oral presentation
- 第19回生体機能研究会, Sep. 2020Srcファミリーキナーゼ、Ras, mTORC1シグナルによる腸上皮細胞の恒常性制御Oral presentation
- 第19回生体機能研究会, Sep. 2020抗SIRPα抗体を用いた膀胱がんに対する新規がん免疫療法開発Oral presentation
- 第93回日本生化学会大会細胞間シグナルCD47-SIRPα系を制御する大環状ペプチドの創出と抗腫瘍剤としての応用Poster presentation
- 第93回日本生化学会大会腸上皮細胞の増殖・分化制御におけるK-Ras活性の役割Poster presentation
- 第78回日本癌学会総会, Sep. 2019SIRPα抗体を用いた新規のがん免疫療法:CD20及びPD-1抗体との併用による有効性Oral presentation
- 第78回日本癌学会総会, Sep. 2019A nobel macrocycle peptide targets CD47-SIRPalpha axis and enhances the macrophage-mediated tumor killingPoster presentation
- 第78回日本癌学会総会, Sep. 2019Role of Tsc2-mTORC1 signaling in regulation of colonic epithelial homeostasisPoster presentation
- 第92回日本生化学会大会, Sep. 2019Regulation by macrophages of the hematopoietic cell lifespan and its therapeutic applicationNominated symposium
- 第92回日本生化学会大会, Sep. 2019Regulation of innate immune cell functions by the SHP-1/2 binding protein SIRPαNominated symposium
- 第92回日本生化学会大会, Sep. 2019Importance of SIRPα+ dendric cells for the development of fibroblastic reticular cells of peripheral lymph nodesOral presentation
- 第18回生体機能研究会, Jul. 2019新規SIRPα阻害剤の開発とその抗腫瘍効果Oral presentation
- 第9回ホスファターゼ研究会学術集会, Jul. 2019SIRPα陽性樹状細胞による末梢リンパ節ストローマ細胞の発達制御Oral presentation
- 第9回ホスファターゼ研究会学術集会, Jul. 2019大腸上皮の恒常性制御におけるTsc2-mTORC1シグナルの役割Oral presentation
- 第9回ホスファターゼ研究会学術集会, Jul. 2019膜型分子SIRPαを標的とする新たな免疫チェックポイント阻害剤の開発Oral presentation
- AACR Annual Meeting 2019, Mar. 2019, English, the American Association for Cancer Research, アトランタ, International conferenceRole of Tsc2-mTORC1 signaling in homeostasis of intestinal epithelium and its relation to inflammation and cancerPoster presentation
- 第47回日本免疫学学術集会, Dec. 2018, English, 日本免疫学会, 福岡, Domestic conferenceSIRPα+Dendritic Cells regulate organization of lymph node stromal sells in vivoOral presentation
- 第47回日本免疫学学術集会, Dec. 2018, English, 日本免疫学会, 福岡, Domestic conferenceImportance of SIRPα on dendritic cells for the development of exprerimental autoimmune encephalomyelitisOral presentation
- 第80回日本血液学会学術集会, Oct. 2018, English, 日本血液学会, 大阪, Domestic conferenceSIRPα陽性樹状細胞による脾臓細網線維芽細胞の恒常性の制御Poster presentation
- Workshop on Frontiers in Phosphatase Research and Drug Discovery, Oct. 2018, English, 日本プロテインホスファターゼ研究会, 東京, International conferenceRole of the tyrosine phosphorylation signal in homeostasis of intestinal epithelium and its relation to inflammation and cancerOral presentation
- Workshop on Frontiers in Phosphatase Research and Drug Discovery, Oct. 2018, English, 日本プロテインホスファターゼ研究会, 東京, International conferenceCritical role of SIRPαon dendritic cells for the development of experimental autoimmune encephalomyelitisPoster presentation
- 第91回日本生化学会大会, Sep. 2018, English, 日本生化学会, 京都, Domestic conference腸上皮細胞の恒常生維持に関わるチロシンリン酸化シグナルの意義Oral presentation
- 第77回日本癌学会学術総会, Sep. 2018, English, 日本癌学会, 大阪, Domestic conference腸炎症制御における腸上皮Srcファミリーキナーゼの役割Poster presentation
- 第91回日本生化学会大会, Sep. 2018, English, 日本生化学会, 京都, Domestic conference常在細菌による成体マウス脳室下帯におけるニュートロン新生の制御Poster presentation
- 第77回日本癌学会学術総会, Sep. 2018, Japanese, 日本癌学会, 大阪, Domestic conferenceTsc2-mTORC1シグナルによる小腸上皮の恒常性制御Poster presentation
- 第91回日本生化学会大会, Sep. 2018, Japanese, 日本生化学会, 京都, Domestic conferenceSrcファミリーキナーゼの炎症性腸疾患における重要性Poster presentation
- 第17回生体機能研究会, Jul. 2018, Japanese, 生体機能研究会, 渋川, Domestic conference実験的自己免疫性脳脊髄炎の発症制御におけるCD47-SIRPα系の役割についてOral presentation
- 第17回生体機能研究会, Jul. 2018, Japanese, 生体機能研究会, 渋川, Domestic conference抗SIRPα抗体による新規がん免疫療法Oral presentation
- 15th International Symposium on Dendritic Cells, Jun. 2018, Japanese, Aachen, International conferenceSIRPα+Dendritic Cells regulate homeostasis of fibroblastic reticular cells via TNF receptor ligands in the adult spleenPoster presentation
- 第65回日本生化学会近畿支部例会, May 2018, Japanese, The Japanese Biochemical Society, Kinki Branch, 西宮, Domestic conferenceRole of Csk iRole of Csk in the regulation of intestinal homeostasis and the development of inflammation in the colonn the regulation of intestinal homeostasis and the development of inflammation in the colonPoster presentation
- The 2nd International Joint Symposium -UW,UO,KU-, Mar. 2018, English, Center for Cell Signaling and Medical Innovation, Honolulu, USA(Hawaii), International conferenceSIRPα+ dendritic cells regulate homeostasis of fibroblastic reticular cells via TNF receptor ligands in the adult spleenPoster presentation
- The 2nd International Joint Symposium -UW,UO,KU-, Mar. 2018, English, Center for Cell Signaling and Medical Innovation, Honolulu, USA(Hawaii), International conferenceRegulation of intestinal epithelial cell turnover by intertinal contentsPoster presentation
- ConBio2017(The 90th Annual Meeting of the Japanese Biochemical Society, The 40th Annual Meeting of the Molecular Biology Society of Japan), Dec. 2017, Japanese, The Japanese Biochemical Society, The Molecular Biology Society of Japan, 神戸, Domestic conferenceDevelopment of a novel cancer immunotherapy targeting the interaction between tumor cells and macrophagesOral presentation
- The 46th Annual Meeting of The Japanese Society for Immunology, Dec. 2017, English, Japanese Society for Immunology, 仙台, Domestic conferenceSIRPα+ dendritic cells regulate homeostasis of fibroblastic reticular cells via TNF receptor ligands in the adult spleenOral presentation
- ConBio2017(The 90th Annual Meeting of the Japanese Biochemical Society, The 40th Annual Meeting of the Molecular Biology Society of Japan), Dec. 2017, English, The Japanese Biochemical Society, The Molecular Biology Society of Japan, 神戸, Domestic conferenceRole of Tsc2-mTORC1 signaling in regulation of intestinal epithelial homeostasisPoster presentation
- The 46th Annual Meeting of The Japanese Society for Immunology, Dec. 2017, English, Japanese Society for Immunology, 仙台, Domestic conferenceDevelopment of a novel primary culture system for lymphoid organ fibroblastic reticular cellsPoster presentation
- The 5th Annual Meeting of the International Cytokine and Interferon Society, ICIS 2017 5th Annual Meeting of the International Cytokine and Interferon Society, ICIS 2017, Nov. 2017, English, International Cytokine and Interferon Society, 金沢, International conferenceSIRPα+ dendritic cells regulate homeostasis of fibroblastic reticular cells via TNF receptor ligands in the adult spleenOral presentation
- The 3rd Japan-Taiwan Bilateral Conference on Protein Phosphatase in Sendai. The 8th Japanese Conference on Protein Phosphatase., Nov. 2017, English, Japanese Association for Protein Phosphatase Research, 仙台, International conferenceRole of mechanistic target of rapamycin complex 1 (mTORC1) in regulation of intestinal epithelial homeostasisOral presentation
- なし, Sep. 2017, Japanese, なし, 岐阜, Domestic conference免疫系ヒト化マウスを用いた新規がん異種移植マウスモデルの作成Oral presentation
- なし, Sep. 2017, Japanese, なし, 岐阜, Domestic conference二次リンパ組織ストローマ細胞の新規初代培養系の樹立と増殖・制御機構の解明Oral presentation
- なし, Sep. 2017, Japanese, なし, 岐阜, Domestic conference腸内容物による腸上皮細胞のターンオーバー制御Oral presentation
- The 76th Annual Meeting of the Japanese Cancer Association, Sep. 2017, Japanese, The Japanese Cancer Association, 横浜, Domestic conferenceRole of Tsc2-mTORC1 signaling in intestinal homeostasisPoster presentation
- The 76th Annual Meeting of the Japanese Cancer Association, Sep. 2017, English, The Japanese Cancer Association, 横浜, Domestic conferenceAnti-SIRPalpha antibodies provide a basis for new approaches to canser immunotherapy,Oral presentation
- The 76th Annual Meeting of the Japanese Cancer Association, Sep. 2017, Japanese, The Japanese Cancer Association, 横浜, Domestic conferenceEstablishment of a potential new PDX mouse model for personalized cancer immunotherapyOral presentation
- The 76th Annual Meeting of the Japanese Cancer Association, Sep. 2017, English, The Japanese Cancer Association, 横浜, Domestic conferenceRegulation of interestinal epithelial homeostasis by Src family kinases through Rac and YAPOral presentation
- なし, Jul. 2017, Japanese, なし, 淡路, Domestic conference受容体型チロシンホスファターゼSAP-1による腸管免疫制御Oral presentation
- Europhosphatase 2017:Phosphatases in cell fates and decisions, Jul. 2017, English, FASEB, Paris, France, International conferenceRole of Src family kinases in regulation of intestinal epithelial homeostasisPoster presentation
- Europhosphatase 2017:Phosphatases in cell fates and decisions, Jul. 2017, English, FASEB, Paris, France, International conferenceRegulation of intestinal immunity by the microvillus-specific protein tyrosine phosphatase SAP-1 and its substrate CEACAM20Poster presentation
- Europhosphatase 2017:Phosphatases in cell fates and decisions, Jul. 2017, English, FASEB, Paris, France, International conferenceBlockage of CD47-SIRPαsignaling provide a novel cancer immunotherapyOral presentation
- The 45th Annual Meeting of the Japanese Society for Immunology, Dec. 2016, English, Japanese Society for Immunology, 宜野湾, Domestic conferenceRole of SIRPα on dendritic cells in homeostatic regulation of fibroblastic reticular cells in the spleenPoster presentation
- The 12th International Conference on Protein Phosphatase, Oct. 2016, English, Japanese Association for Protein Phosphatase Research, 大阪, Domestic conferenceTherapeutic application of anti-SIRPαantibody in cancer treatmentPoster presentation
- The 75 th Annual Meeting of the Japanese Cancer Association, Oct. 2016, Japanese, 日本癌学会, 横浜, Domestic conferenceTherapeautic application of anti-SIRPα antibody in cancer treatment. The 12th International Conference on Protein PhosphataseOral presentation
- The 12th International Conference on Protein Phosphatase, Oct. 2016, Japanese, プロテインフォスファターゼ学術集会, 大阪, Domestic conferenceTherapeautic application of anti-SIRPα antibody in cancer treatmentOral presentation
- The 75th Annual Meeting of the Japanese Cancer Association, Oct. 2016, Japanese, The Japanese Cancer Association, 横浜, Domestic conferenceThe anti-SIRPα antibody prevents tumor formation: a novel strategy for cancer therapyOral presentation
- The 12th International Conference on Protein Phosphatase, Oct. 2016, English, Japanese Association for Protein Phosphatase Research, 大阪, Domestic conferenceRole of Src family kinases in regulatin of intestinal epithelial homeostasisOral presentation
- The 12th International Conference on Protein Phosphatase, Oct. 2016, English, Japanese Association for Protein Phosphatase Research, 大阪, Domestic conferenceRole of SIRPαin the homeostasis of fibroblastic reticular cells by dendritic cells in the spleenPoster presentation
- The 59th Annual Meeting of the Japan Neuroscience Society, Sep. 2016, Japanese, Japanese Society of Biological Psychiatry, The Japanese Society for Neurochemistry, 福岡, Domestic conference白質におけるミクログリア恒常性制御Poster presentation
- The 89th Annual Meeting of the Japanese Biochemical Society, Sep. 2016, Japanese, The Japanese Biochemical Society, 仙台, Domestic conferenceRole of the CD47-SIRPalpha system and its therapeutic applicationOral presentation
- The 59th Annual Meeting of the Japan Neuroscience Society, Sep. 2016, Japanese, Japanese Society of Biological Psychiatry, The Japanese Society for Neurochemistry, 福岡, Domestic conferenceSIRPα欠損マウスはLPS投与によって誘導される低体温症が重症化するPoster presentation
- The 89th Annual Meeting of the Japanese Biochemical Society, Sep. 2016, Japanese, The Japanese Biochemical Society, 仙台, Domestic conferenceShort chain fatty acids regulate the turnover of intestinal epithelial cellsPoster presentation
- なし, Jul. 2016, English, なし, 淡路, Domestic conferenceRole of SIRPαon dendritic cells in homeostatic regulation of fibroblastic reticular cells in the spleenOral presentation
- The 7th Annual Meeting of Japanese Association for Protein Phosphatase Research, Jan. 2016, Japanese, Japanese Association for Protein Phosphatase Research, 岡崎, Domestic conferenceRegulation by microbiota of the cellular life span in intestinal epithelial cellsOral presentation
- The 7th Annual Meeting of Japanese Association for Protein Phosphatase Research, Jan. 2016, English, Japanese Association for Protein Phosphatase Research, 岡崎, Domestic conferenceEssential Role of SIRPα on Dendritic Cells in Homeostatic Regulation of Spleen Stromal CellsPoster presentation
- BMB2015 Biochemistry and Molecular Biology, Dec. 2015, Japanese, The Molecular Biology Society of Japan,The Japanese Biochemical Society, 神戸, Domestic conferenceRole of C-terminal Src kinase(Csk) and Src family kinases in homeostasis of the intestinal epitheliumPoster presentation
- BMB2015 Biochemistry and Molecular Biology, Dec. 2015, Japanese, The Molecular Biology Society of Japan,The Japanese Biochemical Society, 神戸, Domestic conferenceRole of C-terminal Src kinase(Csk) and Src family kinases in homeostasis of the intestinal epitheliumOral presentation
- BMB2015 Biochemistry and Molecular Biology, Dec. 2015, Japanese, The Molecular Biology Society of Japan,The Japanese Biochemical Society, 神戸, Domestic conferenceImportance of commensal bacteria and short-chain fatty acids for the growth and migration of intestinal epithelial cellsPoster presentation
- BMB2015 Biochemistry and Molecular Biology, Dec. 2015, Japanese, The Molecular Biology Society of Japan,The Japanese Biochemical Society, 神戸, Domestic conferenceRegulation of intestinal immunity by R3-subtype receptor-type protein tyrosine phosphatase SAP-1Public symposium
- The 74th Annual Meeting of the Japanese Cancer Association, Oct. 2015, Japanese, The Japanese Cancer Association, 名古屋, Domestic conferenceRole of C-terminal Src kinase(Csk) and Src family kinases in homeostasis of the intestinal epitheliumOral presentation
- The 74th Annual Meeting of the Japanese Cancer Association, Oct. 2015, Japanese, The Japanese Cancer Association, 名古屋, Domestic conferenceImportance of commensal bacteria and short-chain fatty acids for the growth and migration of intestinal epithelial cellsOral presentation
- 2015 FASEB Science Research Conferences, Aug. 2015, English, FASEB, SteamboatSprings, USA, International conferenceSAP-1 and CEACAM20 protect against colitis in the intestinal epitheliumPoster presentation
- 2015 FASEB Science Research Conferences, Aug. 2015, English, FASEB, SteamboatSprings, USA, International conferenceRole of C-terminal Src kinase(Csk) and Src family kinases in homeostasis of the intestinal epitheliumPoster presentation
- The 67th Annual Meeting of the Japan Society for Cell Biology, Jul. 2015, Japanese, The Japan Society for Cell Biology, 東京, Domestic conferenceRegulation of intestinal immunity by the microvillus-specific protein tyrosine phosphatase SAP-1 and CEACAM20Poster presentation
- The 67th Annual Meeting of the Japan Society for Cell Biology, Jul. 2015, Japanese, The Japan Society for Cell Biology, 東京, Domestic conferenceRegulation by microbiota of the cellular life span in intestinal epithelial cellsPoster presentation
- The 38th Annual Meeting of the Japan Neuroscience Society, Jul. 2015, English, The Japan Neuroscience Society, 神戸, Domestic conferenceBehavioral analysis of forebrain neuron-specific Shp2 conditional knockout micePoster presentation
- なし, Jul. 2015, Japanese, なし, 箱根, Domestic conference細胞間シグナル伝達システムCD47-SIRPα系のがん治療への応用Oral presentation
- The 38th Annual Meeting of the Japan Neuroscience Society, Jul. 2015, English, The Japan Neuroscience Society, 神戸, Domestic conferenceAnalysis of cell-cell interaction signal that regulates microglial homeostasisPoster presentation
- The 5th International Symposium on Carcinogenic SpiralInfection, Immunity, and Cancer, Feb. 2015, English, Carcinogenic Spiral, 神戸, International conferenceRole of the protein tyrosine phosphatase Shp2 in homeostasis of the intestinal epitheliumPoster presentation
- University of Washington and Kobe UniversityInternational Joint Symposium, Dec. 2014, English, Kobe University, 神戸, International conferenceRegulation of intestinal immunity by the protein tyrosine phosphatase SAP-1Oral presentation
- The 43rd Annual Meeting of The Japanese Society for Immunology, Dec. 2014, English, Japanese Society for Immunology, 京都, Domestic conferenceEssential role og SIRPα on dendritic dells in organization and homeostasis of the spleenOral presentation
- 第43回日本免疫学会学術集会, Dec. 2014, English, 日本免疫学会, 大阪, Domestic conferenceEssential role of SIRP on dendritic cells in organization and homeostasis of the spleenOral presentation
- The 37th Annual Meeting of the Molecular Biology Society of Japan, Nov. 2014, Japanese, The Molecular Biology Society of Japan, 横浜, Domestic conferenceRegulation by CD-SIRPα signaling of hematopoietic and immune systemsPublic symposium
- 11th International Conference on Protein PhosphataseProtein Phosphatases in Health and Diseases, Nov. 2014, English, Japanese Association for Protein Phosphatase Research, 仙台, International conferenceShear stress-induced redistribution of VE-PTP in endothelial cell and its role in cell elongationOral presentation
- 11th International Conference on Protein PhosphataseProtein Phosphatases in Health and Diseases, Nov. 2014, English, Japanese Association for Protein Phosphatase Research, 仙台, International conferenceRoles of protein throsine phosphatases in homeostasis of intestinal epitheliumOral presentation
- 11th International Conference on Protein PhosphataseProtein Phosphatases in Health and Diseases, Nov. 2014, English, Japanese Association for Protein Phosphatase Research, 仙台, International conferenceRegulation by the intestinal microflora of Carcinoembryonic antigen-related cell adhesion molecule (CEACAM) 20 expression in intestinal epithelial cellsPoster presentation
- The 37th Annual Meeting of the Molecular Biology Society of Japan, Nov. 2014, English, The Molecular Biology Society of Japan, 横浜, Domestic conferenceRegulation by microbiota of intestinal epithelium turnoverPoster presentation
- 11th International Conference on Protein PhosphataseProtein Phosphatases in Health and Diseases, Nov. 2014, English, Japanese Association for Protein Phosphatase Research, 仙台, International conferenceFunctinal analysis of protein tyrosine phosphatase Shp2 in post-mitotic neuronsOral presentation
- The 87th Annual Meeting of the Japanese Biochemical Society, Oct. 2014, Japanese, The Japanese Biochemical Society, 京都, Domestic conferenceRoles of the protein tyrosine phosphatase Shp2 in maintaining homeostasis of the intestinal epitheliumOral presentation
- The 87th Annual Meeting of the Japanese Biochemical Society, Oct. 2014, Japanese, The Japanese Biochemical Society, 京都, Domestic conferenceExpression of CEACAM20 in intestine epithelial cells and regulation of its expression by intestinal microfloraOral presentation
- 第87回 日本生化学会大会, Oct. 2014, Japanese, 日本生化学会, 京都, Domestic conferenceExpression of CEACAM20 in intestinal epithelial cells and regulation of its expression by intestinal microfloraPoster presentation
- The 73rd Annual Meeting of the Japanese Cancer Association, Sep. 2014, English, The Japanese Cancer Association, 横浜, Domestic conferenceRoles of the protein tyrosine phosphatase VE-PTP in endothelial Cells of tumor vessels and normal their counterpartsOral presentation
- 第73回日本癌学会学術総会, Sep. 2014, English, がん研究会, 神奈川, Domestic conferenceShp2ホスファターゼはRas活性化を介して腸上皮の恒常性と腸炎発症を制御するOral presentation
- Neuroscience 2014The 37th Annual Meeting of the Japan Neuroscience Society, Sep. 2014, English, The Japan Neuroscience Society, 横浜, Domestic conferenceRegulation of microglial homeostasis through cell-cell interaction signalPoster presentation
- Neuroscience 2014The 37th Annual Meeting of the Japan Neuroscience Society, Sep. 2014, English, The Japan Neuroscience Society, 横浜, Domestic conferenceFunctional Analysis of protein tyrosine phosphatase Shp2 in the adult forebrain neuronsOral presentation
- なし, Jul. 2014, Japanese, なし, 岐阜, Domestic conference腸管におけるCDACAM20の発現と腸内細菌叢を介した発現制御Oral presentation
- なし, Jul. 2014, Japanese, なし, 岐阜, Domestic conference樹状細胞及び二次リンパ組織の恒常維持におけるSIRPαの役割Oral presentation
- The 66th Annual Meeting of the Japan Society for Cell Biology, Jun. 2014, Japanese, The Japan Society for Cell Biology, 奈良, Domestic conferenceRoles of the protein tyrosine phosphatase Shp2 in maintaining homeostasis of the intestinal epitheliumOral presentation
- The 66th Annual Meeting of the Japan Society for Cell Biology, Jun. 2014, Japanese, The Japan Society for Cell Biology, 奈良, Domestic conferenceShear Stress-induced Redistribution of Vascular Endothelial-Protein-tyrosine Phosphatase (VE-PTP) in Endothelial Cells and Its Role in Cell Elongation.Oral presentation
- The 18th International Vascular Biology Meeting(IVBM2014), Apr. 2014, English, International Vascular Biology Meeting, 京都, International conferenceShear Stress-induced Redistribution of Vascular Endothelial-Protein-tyrosine Phosphatase (VE-PTP) in Endothelial Cells and Its Role in Cell Elongation.Poster presentation
- University of Washington-Kobe University Symposium on Membrane biology, Mar. 2014, English, University of Washington-Kobe University, Seattle, USA, International conferenceSIRPα-CD47 system regulates the homeostasis of dendritic cells in lymphoid tissuesPoster presentation
- The 2nd University of Washington-Kobe University Joint Symposium on Membrane Biology, Mar. 2014, English, University of Washington, Seattle, USA, International conferenceSIRPα-CD47 system regulates the homeostasisof dendritic cells in lymphoid tissuesPoster presentation
- University of Washington-Kobe University Symposium on Membrane biology, Mar. 2014, English, University of Washington-Kobe University, Seattle, USA, International conferenceRole of VE-PTP in shear stress responses of endothelial cellsPoster presentation
- The 6th Annual Meeting of Japanese Association for Protein Phosphatase Research, Feb. 2014, Japanese, Japanese Association for Protein Phosphatase Research, 三重, Domestic conference腸上皮の恒常性維持におけるチロシンホスファターゼShp2の役割Oral presentation
- The 6th Annual Meeting of Japanese Association for Protein Phosphatase Research, Feb. 2014, Japanese, Japanese Association for Protein Phosphatase Research, 三重, Domestic conference樹状細胞及び二次リンパ組織の恒常性維持におけるSIRPαの役割Oral presentation
- The 6th Annual Meeting of Japanese Association for Protein Phosphatase Research, Feb. 2014, Japanese, Japanese Association for Protein Phosphatase Research, 三重, Domestic conference細胞質型チロシンホスファターゼShp2による脳機能制御Oral presentation
- Annual Meeting of the Japanese Society for Immunology, 2013, Dec. 2013, English, Japanese Society for Immunology, 千葉, Domestic conferenceSIRPα-CD47 system regulates the homeostasis of dendritic cells in lymphoid tissuesPoster presentation
- The 36th Annual Meeting of the Molecular Biology Society of Japan, Dec. 2013, Japanese, The Molecular Biology Society of Japan, 兵庫, Domestic conferenceR3 受容体型チロシンホスファターゼの発現、局在と生理機能[Invited]Nominated symposium
- The 72rd Annual Meeting of the Japanese Cancer Association, Oct. 2013, Japanese, The Japanese Cancer Association, 神奈川, Domestic conferenceRoles of the protein tyrosine phosphatase Shp2 in maintaining 213 homeostasis of the intestinal epitheliumOral presentation
- The 72rd Annual Meeting of the Japanese Cancer Association, Oct. 2013, Japanese, The Japanese Cancer Association, 神奈川, Domestic conferenceRegulation of intestinal immunity by the protein tyrosine phosphatase SAP-1Oral presentation
- The 86th Annual Meeting of the Japanese Biochemical Society, Sep. 2013, Japanese, The Japanese Biochemical Society, 神奈川, Domestic conferenceRoles of the protein tyrosine phosphatase Shp2 in maintaining homeostasis of the intestinal epitheliumOral presentation
- The 86th Annual Meeting of the Japanese Biochemical Society, Sep. 2013, Japanese, The Japanese Biochemical Society, 神奈川, Domestic conferenceMolecular basis for regulation of the life span of intestinal epithelial cell[Invited]Nominated symposium
- The 60th Annual Meeting of KITAKANTO Medical Society, Sep. 2013, Japanese, KITAKANTO Medical Society, 群馬, Domestic conference細胞質型チロシンホスファターゼShp2の成熟脳における機能解析Poster presentation
- The 86th Annual Meeting of the Japanese Biochemical Society, Sep. 2013, English, The Japanese Biochemical Society, 神奈川, Domestic conferenceRole of VE-PTP in shear stress responses of endothelial cellsOral presentation
- The 60th Annual Meeting of KITAKANTO Medical Society, Sep. 2013, Japanese, KITAKANTO Medical Society, 群馬, Domestic conferenceSIRPαによる脾臓T細胞の恒常性の調節Poster presentation
- 2013 FASEB Science Research Conferences, Aug. 2013, English, FASEB, SteambatSprings(Colorad), USA, International conferenceRoles of the protein tyrosine phosphatase Shp2 in homeostasis of the intestinal epitheliumPoster presentation
- 2013 FASEB Science Research Conferences, Aug. 2013, English, FASEB, SteambatSprings(Colorad), USA, International conferenceMicrobiota modulates the turnover of intestinal epithelial cellsPoster presentation
- 第12回生体機能研究会, Jul. 2013, Japanese, 生体機能研究会, 群馬, Domestic conference腸上皮の恒常性維持におけるチロシンホスファターゼShp2の役割Oral presentation
- The 36th annual Meeting of the Japan Neuroscience SocietyThe 56th Annual Meeting of Japanese Society for NeurochemistryThe 23rd Annual Conference of Japanese Neural Network Society, Jun. 2013, English, The Japan Neuroscience Society, 京都, Domestic conferenceHypthermia−dependent and −independent effects of forced swim on the phosphorylation satates of signaling molecules in mouse hippocampusPoster presentation
- The 36th annual Meeting of the Japan Neuroscience SocietyThe 56th Annual Meeting of Japanese Society for NeurochemistryThe 23rd Annual Conference of Japanese Neural Network Society, Jun. 2013, English, The Japan Neuroscience Society, 京都, Domestic conferenceFunctional Analysis of A non-receptor type protein tyrosine phosphatase Shp2 in the adult brainPoster presentation
- 10th International Conference on Protein Phosphatase Protein Phosphatases and Diseases, Feb. 2013, English, Japanese Association for Protein Phosphatase Research, 東京, CEACAM20 is an immunoglobulin-superfamily transmembrane protein that contains the ITAM-like motif in its cytoplasmic region. We have recently found that CEACAM20 is a putative substrate of SAP-1, a receptor type tyrosine phosphatase, in mouse intestinal epithelial cells. However, tyrosine phosphorylation of CEACAM20 and its physiological significance remain largely unknown. Her, International conferenceTyrosine phosphorylation of CEACAM20 and its functional rolesPoster presentation
- 10th International Conference on Protein Phosphatase Protein Phosphatases and Diseases, Feb. 2013, English, Japanese Association for Protein Phosphatase Research, 東京, Protein tyrosine phosphatase Shp2 expresses ubiquitously, and promotes the activation of the Ras-MAPK cascade by growth factor and cytokine stimulation. Shp2 regulates proliferation and differentiation via Ras/MAPK cascade, and Shp2 deficient mice were embryonic lethal. Shp2 also is abundantly expressed in the adult brain, and Shp2 activity promotes differentiation of neuronal, International conferenceHypothermia-induced tyrosine phosphorylation of SIRPα in the brainPoster presentation
- 10th International Conference on Protein Phosphatase Protein Phosphatases and Diseases, Feb. 2013, English, Japanese Association for Protein Phosphatase Research, 東京, Dendritic cells (DCs) promote immune responses to foreign antigens (Ags) and immune tolerance to self-Ags. Deregulation of DCs is implicated in autoimmunity, but the molecules that regulate DCs to protect against autoimmunity have remained unknown. In this study, we show that mice lacking the protein tyrosine phosphatase Shp1 specifically in DCs develop splenomegaly associated, International conferenceDendritic cell-specific ablation of the protein tyrosine phosphatase Shp1 promotes Th1 cell diffierentiation and induces autoimmunityPoster presentation
- The 85th Annual Meeting of the Japanese Biochemical Society, Dec. 2012, Japanese, The Japanese Biochemical Society, 福岡, SIRPα(Signal regulatory proteinα)は、樹状細胞やマクロファージに発現する膜タンパク質であり、その細胞外領域のリガンドである膜タンパク質CD47と相互作用し、細胞間相互作用シグナルCD47-SIRPα系を構成する。今回我々は、SIRPαノックアウト(KO)マウスの脾臓において、白脾髄の縮小と、CD4陽性T細胞数の減少を見出した。また、脾臓T細胞領域のストローマ細胞が産生するケモカインであるCCL19およびCCL21、サイトカインであるIL-7の遺伝子発現量の減少も見出した。同様のフェノタイプは、SIRPαのリガンドであるCD47のKOマウスでも認められた。これらの結果から、CD47-SIRPα系が、T細胞の恒常性維持に関与する可能性が考えられた。さらに、SIRPα KOと野生型マウスの間で作製した骨髄キメラマウスを解析, Domestic conferenceSignal regulatory protein alpha regulates the homeostasis of T lymphocytes in the spleen.Poster presentation
- 11th biennial meeting of APSN/55th Meeting of JSN, Oct. 2012, Japanese, The Japanese Society for Neurochemistry, The Asian Pacific Society of Nephrology, 兵庫, Signal regulatory protein a (SIRPa also known as SHPS-1, BIT, or P84) is a neuronal membrane protein that has three immunoglobulin-like domains in its extracellular region and tyrosine phosphorylation sites in the cytoplasmic region. Tyrosine phosphorylated SIRPa binds and activates protein tyrosine phosphatase Shp2. Previously, we found that SIRP a undergoes tyrosine phosphory, International conferenceHypothermia-induced tyrosine phosphorylation of SIRPa in the brainOral presentation
- 欧州リウマチ学会議2012, Jun. 2012, English, The European League Against Rheumatism, Berlin, Germany, Background: Dendritic cells (DCs) are professional antigen-presenting cells crucial for initiating immune response to pathogens as well as for maintaining immune tolerance to self-antigens. Dysregulation of the function of DCs is thought to cause abnormal immune responses to self-antigens, which in turn cause autoimmunity. Src homology 2 domaincontaining protein tyrosine phosph, International conferenceImportance of The Protein Tyrosine Phosphatase Shp1 In Dendritic Cells for Prevention of Th1 Cell Differentiation And Autoimmunity: A Potential Target for the TherapyOral presentation
- 第5回プロテインホスファターゼ研究会 学術集会 大阪, Jan. 2012, Japanese, 日本プロテインホスファターゼ研究会, 吹田市, Domestic conference腸微絨毛特異的な発現を示す受容体型チロシンホスファターゼSAP-1による腸管免疫制御Oral presentation
- 第5回プロテインホスファターゼ研究会 学術集会 大阪, Jan. 2012, Japanese, 日本プロテインホスファターゼ研究会, 吹田市, Domestic conference成熟脳におけるShp2の生理機能解析Oral presentation
- 第2回国際放射線神経生物学会大会, Dec. 2011, Japanese, International Society of Radiation Neurobiology, 前橋市, International conference蛋白質チロシンホスファターゼShp2の成熟脳における機能解析Poster presentation
- 第40回日本免疫学会学術集会, Nov. 2011, English, 日本免疫学会, 千葉市(幕張), Domestic conferenceDendritic cell-specific depletion of protein tyrosine phosphatase Shp1 promotes Th1 differentiation causes autoimmunityPoster presentation
- 群馬大学・秋田大学連携グローバルCOEプログラム「生体調節シグナルの統合的研究」第5回グローバルCOE若手研究者シンポジウム, Aug. 2011, Japanese, GCOEプログラム, 秋田市, Domestic conference血管内皮細胞のシェアストレス刺激応答におけるVE-PTPの機能解析Oral presentation
- 第10回生体機能研究会, Jul. 2011, Japanese, 生体機能研究会, 美馬市穴吹町, Domestic conferenceチロシンホスファターゼSAP-1の機能と病態Invited oral presentation
- 発がんスパイラル第1回国際シンポジウム第11回プロテインホスファターゼ国際カンファレンス, Feb. 2011, English, 東京, International conferenceShear stress regulates cellular localization of vascular endothelial-protein tyrosine phosphatase (VE-PTP)Oral presentation
- 発がんスパイラル第1回国際シンポジウム第10回プロテインホスファターゼ国際カンファレンス, Feb. 2011, English, 東京, International conferenceHypothermia-induced tyrosine phosphorylation of SIRPα in the brainPoster presentation
- 第1回放射線神経生物学研究集会, Jan. 2011, Japanese, 群馬, Domestic conference神経細胞間相互作用シグナルCD47-SIRPα系による脳のストレス応答制御機構Poster presentation
- BMB2010第33回日本分子生物学会年会第83回日本生化学会大会合同年会, Dec. 2010, Japanese, 日本分子生物学会・日本生化学会, 神戸, 日本, Domestic conference低温ストレスによるSIRPαチロシンリン酸化の誘導Poster presentation
- BMB2010第33回日本分子生物学会年会第85回日本生化学会大会合同年会, Dec. 2010, Japanese, 日本分子生物学会・日本生化学会, 神戸, 日本, Domestic conference腸微絨毛特異的な発現を示す受容体型チロシンキナーゼSAP-1とIL-10による炎症性腸疾患の制御Poster presentation
- BMB2010第33回日本分子生物学会年会第84回日本生化学会大会合同年会, Dec. 2010, Japanese, 日本分子生物学会・日本生化学会, 神戸, 日本, Domestic conference血管内皮細胞のシェアストレス刺激応答におけるVE-PTPの機能解析Oral presentation
- BMB2010第33回日本分子生物学会年会第85回日本生化学会大会合同年会, Dec. 2010, Japanese, 日本分子生物学会・日本生化学会, 神戸, 日本, Domestic conferenceチロシンリン酸化シグナルによる脳のストレス応答制御機構Oral presentation
- 群馬大学・秋田大学連携グローバルCOEプログラム「生体調節シグナルの統合的研究」第4回グローバルCOE若手研究者シンポジウム, Nov. 2010, Japanese, 秋田, Domestic conferenceチロシンリン酸化シグナルによる脳のストレス応答制御機構Oral presentation
- 40th Annual Meeting of Society for Neuroscience,Neuroscience 2010, Nov. 2010, English, Society for Neuroscience, サンディエゴ, アメリカ, International conferenceStress-evoked tyrosine phosphorylation of SIRPα mediates an antidepressant effectPoster presentation
- 第57回北関東医学会総会, Oct. 2010, Japanese, 北関東医学会, 群馬, Domestic conference脳におけるSIRPαチロシンリン酸化の解析Poster presentation
- 第一回脳表現型の分子メカニズム研究会, Oct. 2010, Japanese, 大阪, Domestic conferenceCD47-SIRPα系の機能とヒト遺伝子多型Oral presentation
- Neuro 2010(第33回日本神経科学大会、第53回日本神経化学会大会、第20回日本神経回路学会大会、合同大会), Sep. 2010, Japanese, 日本神経回路学会、日本神経化学会、日本神経科学会, 神戸, International conferenceチロシンリン酸化シグナルによる脳のストレス応答制御Oral presentation
- 11th International Symposium on Dendritic Cells in Fundamental and Clinical Immunology, Sep. 2010, English, Institute for Research in Biomedicine, ルガーノ, スイス, International conferenceRegulation by SIRPα of dendritic cell homeostasis in lymphoid tissues.Poster presentation
- 15th International Congress of Immunology, Aug. 2010, English, 日本免疫学会・国際免疫学会連合, 神戸, International conferenceRoles of SIRPα in the homeostatic regulation of mucosal immunity in the intestine.Poster presentation
- 14th International Congress of Immunology, Aug. 2010, English, 日本免疫学会・国際免疫学会連合, 神戸, International conferenceRegulation by SIRPα of homeostasis of lymphoid tissue dendritic cells.Poster presentation
- 第9回生体機能研究会, Jul. 2010, Japanese, 第9回生体機能研究会, 神奈川(箱根), Domestic conference細胞間相互作用シグナルCD47-SIRPα系による脳のストレス応答制御Oral presentation
- FASEB Summer Research Conferences"Protein Phosphatases", Jul. 2010, English, 米国連邦実験生物学会, コロラド, アメリカ, International conferenceStress-evoked tyrosine phosphorylation of SIRPα mediates an antidepressant effectPoster presentation
- FASEB Summer Research Conferences"Protein Phosphatases", Jul. 2010, English, 米国連邦実験生物学会, コロラド, アメリカ, International conferencePromotion of cell spreading and migration by vascular endothelial-protein tyrosine phosphatase (VE-PTP) in cooperation with integrinPoster presentation
- FASEB Summer Research Conferences"Protein Phosphatases", Jul. 2010, English, 米国連邦実験生物学会, コロラド, アメリカ, International conferenceExpression of PTPRO in the interneurons of adult mouse olfactory bulbPoster presentation
- JSH (日本血液学会)International Symposium 2010, Jul. 2010, English, 日本血液学会, 秋田, International conferenceEssential roles of the CD47-SIRPα signaling system for dndritic cell homeostasis in lymphoid tissuesPoster presentation
- 腸上皮細胞の増殖・分化制御におけるK-Ras活性の役割
- 日本学術振興会, 科学研究費助成事業, 基盤研究(C), 神戸大学, 01 Apr. 2022 - 31 Mar. 2025がん微小環境における細胞間シグナルによる腫瘍免疫制御
- Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C), Grant-in-Aid for Scientific Research (C), Kobe University, Apr. 2019 - Mar. 2022Molecular mechanisms underlying an immune evasion by cancer cells via cell-to-cell signalingIn this study, we found that the membrane protein SIRPα functions as a negative regulator of cancer cell phagocytosis by macrophages and their secretion of cytokines involved in the elimination of cancer cells. We also showed that a novel SIRPα-binding peptide specifically bound to SIRPα enhanced the antitumor effect of antibodies against tumor antigens. Furthermore, using an antibody against the membrane proteins SIRPα and SIRPβ, we demonstrated that SIRPβ acted as a positive regulator of macrophage cytotoxic activity toward cancer cells. The antibody was also found to exert an antitumor effect in mouse models of cancer.
- 学術研究助成基金助成金/基盤研究(C), Apr. 2016 - Mar. 2019, Principal investigatorCompetitive research funding
- Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research, Grant-in-Aid for Scientific Research (B), Kobe University, 01 Apr. 2014 - 31 Mar. 2017Molecular basis of the CD47-SIRP alpha signaling system in the regulation of physiological functionWe have here investigated the molecular basis of the CD47-SIRPα signaling system in the regulation of physiological function in the central nervous system (CNS) as well as in the immune system. In the CNS, we have shown that the protein tyrosine phosphatase Shp-2, which is a downstream molecule of SIRPα, regulates synaptic functions and thereby modulates learning and locomotor activity. In the immune system, we have shown that SIRPα is essential for the maintenance of dendritic cell homeostasis in the secondary lymphoid organs and skin. Furthermore, we have found that anti-SIRPα antibodies appear to be a potential new tool for cancer immunotherapy.
- 学術研究助成基金助成金/基盤研究(C), Apr. 2013 - Mar. 2016, Principal investigatorCompetitive research funding
- Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research, Grant-in-Aid for Scientific Research (B), Kobe University, 01 Apr. 2011 - 31 Mar. 2014The integrative research for regulation by protein tyrosine phosphatases of biological functions and its molecular mechanismWe have here performed the integrative research for the biological functions and molecular mechanisms for the protein tyrosine phosphatases SHP-2 as well as the related signaling pathway CD47-SIRPalpha, and R3-receptor type PTPs. We have shown that SHP-2 in the post-mitotic neurons is important for regulation of the neuronal activity. The CD47-SIRPalpha is important for regulation of dendritic cells as well as organization of lymphoid tissues. In addition, VE-PTP is implicated in regulation of endothelial cell functions by shear stress.
- 研究成果最適展開支援プログラム フィージビリティスタディステージ 探索タイプ, 2013, Principal investigatorA-STEP「血管内皮細胞を標的とした新規抗体がん治療法の開発」Competitive research funding
- 研究成果最適展開支援プログラム フィージビリティスタディステージ 探索タイプ, 2012, Principal investigatorA-STEP「血管内皮細胞を標的とした新規抗体がん治療法の開発」Competitive research funding
- 科学研究費補助金/基盤研究(C), 2010, Principal investigatorCompetitive research funding
- Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research, Grant-in-Aid for Scientific Research on Priority Areas, Gunma University, 2005 - 2009Protein tyrosine phosphatases and regulation of cancer cell adhesion/migrationIn this grant project, we have investigated the physiological role of protein tyrosine phosphorylation as well as its relation to oncogenesis and metastasis. We have clarified that a novel cell-cell communication system “CD47-SHPS-1 system" or SAP-1, a receptor-type protein tyrosine phosphatase, is important for regulation of cancer metastasis and of inflammation that is directly related to development of cancers.
- Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research, Grant-in-Aid for Young Scientists (B), Gunma University, 2007 - 2008Molecular mechanism underlying the apical sorting of membrane proteins in epithelial cells本研究では、受容体型チロシンホスファターゼSAP1、PTP-ROをモデルとして、上皮系細胞における膜型分子のアピカル面への局在制御機構の解明を目指した。その結果、SAP1、PTP-ROのアピカル面への局在化には、両者の細胞内領域を除く領域が必須であるが、その一方で、膜型分子の細胞膜上での発現制御に関与するGrb2と相互作用して、アピカル面での局在やその発現が制御される可能性も示唆された。また、SAP1の下流で機能するシグナル分子の同定し、これらの分子がSAP1の局在制御に関与するかについて解析を進めている。
- 日本学術振興会, 科学研究費助成事業, 若手研究(スタートアップ), 群馬大学, 2006 - 2007神経細胞の極性形成におけるRap1の作用機構と生理機能神経細胞は形態的、機能的に異なる軸索と樹状突起を持つ極性細胞であり、その極性形成の一過程である軸索の形成に低分子量G蛋白質の一つであるRap1の関与が示唆されている。本研究では神経細胞の極性形成、および軸索伸長にRap1のGDP/GTP交換因子(GEF)として機能するMR-GEFとPDZ-GEFの関与につき解析を行った。神経細胞の軸索形成や伸長のモデル細胞であるN1E-115細胞は、血清存在下の培養では神経様突起の伸長が抑制され、血清非存在下の培養では突起伸長を示すことが知られている。そこでN1E-115細胞にMR-GEFおよびPDZ-GEFの過剰発現を行い、神経様突起の伸長、細胞形態に対する影響を検討した。その結果、MR-GEF、PDZ-GEFの過剰発現により神経様突起伸長と細胞の伸展の亢進が血清存在下において認められた。また、MR-GEFおよびPDZ-GEFによる神経様突起伸長と細胞の伸展の亢進はRap1GAPとの共発現により抑制されたことから、これらのGEFがRap1の活性化を通じて神経様突起伸長と細胞の伸展を制御することが示唆された。さらに、MR-GEFおよびPDZ-GEFによる神経様突起伸長と細胞の伸展の亢進は、アクチン骨格系の制御分子であるCdc42およびRacのドミナントネガティブ変異体との共発現によって部分的な抑制が認められた。本研究により、MR-GEF、PDZ-GEFがRap1を介してアクチン骨格系を制御し、神経軸索の形成・伸長に関与する可能性が示唆された。