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研究業績詳細

HEISSIG Beate（ハイジッヒベアーテ）

研究テーマ	Role of proteases in normal development and disease
研究業績（論文）	1. Salama Y, Munakata S, Osada T, Takahashi S, Hattori K, Heissig B. Heparin-binding EGF-like growth factor via miR-126 controls tumor formation/growth and the proteolytic niche in murine models of colorectal and colitis-associated cancers. Cell Death & Disease. doi: 10.1038/s41419-024-07126-2, 2024. 2. Skrypnyk M, Yatsenko T, Riabets O, Salama Y, Skikevych M, Osada T, Tobita M, Takahashi S, Hattori K, Heissig B. Heliyon. 29;10(11):e31777. doi: 10.1016/j.heliyon..e31777. eCollection 5, 2024. 3. Yatsenko T, Rios R, Nogueira T, Salama Y, Takahashi S, Adachi E, Tabe Y, Hattori N, Osada T, Naito T, Takahashi K, Hattori K, Heissig B. The influence of 4G/5G polymorphism in the plasminogen-activator-inhibitor-1 promoter on COVID-19 severity and endothelial dysfunction. Front. Immunol., Sec. Inflammation, Volume 15 - doi.org/10.3389/fimmu.2024.1445294 30 August, 2024. 4. Yatsenko T, Rios R, Nogueira T, Salama Y, Takahashi S, Tabe Y, Naito T, Takahashi K, Hattori K, Heissig B. Urokinase-type plasminogen activator and plasminogen activator inhibitor-1 complex as a serum biomarker for COVID-19. Front Immunol. 2024 Jan 11:14:1299792.; Front Immunol. Jan, 2024.11:14:1299792. doi: 10.3389/fimmu.2024.1390698./Corrigendum Front Immunol 2024 Jan 11:14:1299792; Front Immunol.Jan 11:14:1299792;doi: 10.3389/fimmu.2023.1299792, 2024. 5. Mizoue Y, Ikeda T, Ikegami T, Riabets O, Oishi Y, Tobita M, Akutsu H, Hattori K, Heissig B, Koide K. The stem cell transcription factor ZEP296 transforms NIH3T3 cells and promotes anchorage-independent growth of cancer cells. Int J Dev Biol.67(4):147-153. doi: 10.1387/ijdb.230143hk, 2023. 6. Salama Y, Takahashi S, Tsuda Y, Okada Y, Hattori K, and Heissig B. YO2 induces melanoma cell apoptosis through p53-mediated LRP1 downregulation. Cancers 15, 288; doi 10.3390/cancers15010288, 2023. 7. Heissig B, Salama Y, Iakoubov R, Vehreschild JJ, Rios R, Nogueira T, Maria J.G.T. Vehreschild M.J.G.T., Stecher M, Mori H, Lanznaster J, Adachi E, Jakob C, Tabe Y, Ruethrich M, Borgmann S, Naito T, Wille K, Valenti S, Hower M, Hattori N, Rieg S, Nagaoka T, Jensen BE, Yotsuyanagi H, Hertenstein B, Ogawa H, Wyen C, Kominami E, Roemmele C, Takahashi S, Rupp J, Takahashi K, Hanses F, Hattori K and on behalf of the LEOSS study group. COVID-19 Severity and Thrombo-Inflammatory Response Linked to Ethnicity. Biomedicines, 10(10), 2549; doi.org/10.3390/biomedicines10102549, 2022. 8. Heissig B, Salama Y, Tateno M, Takahashi S, Hattori K. siRNA against CD40 delivered via a fungal recognition receptor ameliorates murine acute graft-versus-host disease. eJHaem, Volume 3, Issue3, doi.org/10.1002/jha2.439, 2022. 9. Salama Y, Jaradat N, Hattori K, Heissig B. Aloysia Citrodora Essential Oil Inhibits Melanoma Cell Growth and Migration by Targeting HB-EGF-EGFR Signaling. Int J Mol Sci. Jul 29;22(15):8151,2021. doi: 10.3390/ijms22158151, 2021. 10. Salama Y, Hendrik Heida A, Yokoyama K, Takahashi S, Hattori K, Heissig B. The EGFL7-ITGB3-KLF2 axis enhances myeloma cell survival and contributes to drug resistance. Blood Advances, 24;4(6):1021-1037, 2020. 11. Sato-Okabayashi Y, Isoda K, Heissig B, Kadoguchib T, Akita K, Kitamura K, Shimada K, Hattori K, Daida H. Low-dose oral cyclophosphamide therapy reduces atherosclerosis progression by decreasing inflammatory cells in a murine model of atherosclerosis. Int J Cardiol Heart Vasc. May 10; 28:100529, 2020. 12. Salama Y, Lin SY, Dhahri D, Hattori K, Heissig B. The fibrinolytic factor tPA drives LRP1-mediated melanoma growth and metastasis. FASEB J: 33(3):3465-3480, 2019. 13. Honjo K, Munakata S, Tashiro Y, Salama Y, Shimazu H, Eiamboonsert S, Dhahri D, Ichimura A, Dan T, Miyata T, Takeda K, Sakamoto K, Hattori K, Heissig B. Plasminogen activator inhibitor-1 regulates macrophage-dependent postoperative adhesion by enhancing EGF-HER1 signaling in mice. FASEB J: Jun;31(6):2625-2637, 2017. 14. Shimazu H, Munakata S, Tashiro Y, Salama Y, Dhahri D, Eiamboonsert S, Ota Y, Onoda H, Tsuda Y, Okada Y, Nakauchi H, Heissig B, Hattori K. Pharmacological targeting of plasmin prevents lethality and tissue damage in a murine model of macrophage activation syndrome. Blood: 6;130(1):59-72, 2017. 15. Eiamboonsert S, Salama Y, Watarai H, Dhahri D, Tsuda Y, Okada Y, Hattori K, Heissig B. The role of plasmin in the pathogenesis of murine multiple myeloma. Biochem Biophys Res Commun.: 24:488(2):387-392, 2017. 16. Salama Y, Hattori K, Heissig B. The angiogenic factor Egfl7 alters thymogenesis by activating Flt3 signaling. Biochem Biophys Res Commun.: 19,490(2):209-216, 2017. 17. Dhahri D, Sato-Kusubata K, Ohki-Koizumi Mo, Nishida C, Tashiro Y, Munakata S, Shimazu H, Salama Y, Eiamboonsert S, Nakauchi H, Hattori K#, Heissig B#. Fibrinolytic crosstalk with endothelial cells expands murine mesenchymal stromal cells. Blood: 128(8), 1063-75, 2016.　 18. Munakata S, Tashiro Y, Nishida C, Sato A, Komiyama H, Shimazu H, Dhahri D, Salama Y, Eiamboonsert S, Takeda K, Yagita H, Tsuda Y, Okada Y, Nakauchi H, Sakamoto K, Heissig B#, Hattori K#. Inhibition of Plasmin Protects Against Colitis in Mice by Suppressing Matrix Metalloproteinase 9-mediated Cytokine Release from Myeloid Cells. Gastroenterology: 148(3), 565-578, 2015. 19. Sato A, Nishida C, Sato-Kusubata K, Ishihara M, Tashiro Y, Gritli I, Shimazu H, Munakata S, Yagita H, Okumura K, Tsuda Y, Okada Y, Tojo A, Nakauchi, H, Takahashi S, Heissig B#, Hattori K#. Inhibition of plasmin attenuates murine acute graft-versus-host disease mortality by suppressing the matrix metalloproteinase-9-dependent inflammatory cytokine storm and effector cell trafficking. Leukemia: 29(1), 145-56, 2015. 20. Nakahara F, Kitaura J, Uchida T, Nishida C, Togami K, Inoue D, Matsukawa T, Kagiyama Y, Enomoto Y, Kawabata K C., Chen-Yi L, Komeno Y, Izawa K, Oki T, Nagae G, Harada Y, Harada H, Otsu M, Aburatani H, Heissig B, Hattori K, Kitamura T. Hes1 promotes blast crisis in chronic myelogenous leukemia through MMP-9 upregulation in leukemic cells. Blood: 123(25), 3932-42, 2014. 21. Caiado F, Carvalho T, Rosa I, Remedio L, Costa A, Matos J, Heissig B, Yagita H, Hattori K, da Silva JP, Fidalgo P, Pereira AD, Dias S. Bone Marrow-Derived CD11b+Jagged2+ Cells promote epithelial-to-mesenchymal transition and metastasization in colorectal cancer. Cancer Res.: 73, 4233-4246, 2013. 22. Tashiro Y, Nishida C, Sato-Kusubata K, Ohki-Koizumi M, Ishihara M, Sato A, Gritli I, Komiyama H, Sato Y, Dan T, Miyata T, Okumura K, Tomiki Y, Sakamoto K, Nakauchi H, Heissig B#, Hattori K#. Inhibition of PAI-1 induces neutrophil-driven neoangiogenesis and promotes tissue regeneration via production of angiocrine factors in mice. Blood: 119, 6382-93, 2012. 23. Nishida C, Kusubata K, Tashiro Y, Gritli I, Sato A, Ohki-Koizumi M, Morita Y, Nagano M, Sakamoto T, Koshikawa N, Kuchimaru T, Kizaka-Kondoh S, Seiki M, Nakauchi H, Heissig B#, Hattori K#. MT1-MMP plays a critical role in hematopoiesis by regulating HIF-mediated chemokine-/cytokine gene transcription within niche cells. Blood: 119, 5405-16, 2012. 24. Okaji Y, Tashiro Y, Gritli I, Nishida C, Sato A, Ueno Y, Del Canto Gonzalez S, Ohki-Koizumi M, Akiyama H, Nakauchi, Hattori K#, Heissig B#. Plasminogen deficiency attenuates post-natal erythropoiesis in male C57BL/6 mice through decreased activity of the LH-testosterone axis. Exp. Hematology: 40: 143-154, 2012. 25. Ishihara M, Nishida C, Tashiro Y, Gritli I, Rosenkvist J, Koizumi M, Okaji Y, Yamamoto R, Yagita H, Okumura K, Nishikori M, Wanaka K, Tsuda Y, Okada Y, Nakauchi H, Heissig B#, Hattori K#. Plasmin inhibitor reduces lymphoid tumor growth by suppressing matrix metalloproteinase-9 dependent CD11b+/F4/80+ myeloid cell recruitment. Leukemia: 26, 332–339, 2012. 26. Piao JH, Hasegawa M, Heissig B, Hattori K, Takeda K, Iwakura Y, Okumura K, Inohara N, Nakano H. Tumor necrosis factor receptor-associated factor (Traf)2 controls homeostasis of the colon to prevent spontaneous development of murine inflammatory bowel disease. J Biol Chem: 286, 17879-88, 2011. 27. Ohki M, Ohki Y, Ishihara M, Nishida C, Tashiro Y, Akiyama H, Komiyama H, Lund LR, Nitta A, Yamada K, Zhu Z, Ogawa H, Yagita H, Okumura K, Nakauchi H, Werb Z, Heissig #, Hattori K#. Tissue type plasminogen activator regulates myeloid-cell dependent neoangiogenesis during tissue regeneration. Blood: 115, 4302-4312, 2010. 28. Sato Y, Ohki Y, Akiyama H, Rosenkvist J, Gritli I, Okumura K, Ogawa H, Daida H, Heissig B, Hattori K, Ohsaka A. Targeted deletion of matrix metalloproteinase-9 reduces neutrophil accumulation during G-CSF-induced neoangiogenesis. Cytometry Research: 19(2), 53-62, 2009. 29. Kerbel RS, Benezra R, Lyden DC, Hattori K, Heissig B, Nolan DJ, Mittal V, Shaked Y, Dias S, Bertolini F, Rafii S. Endothelial progenitor cells are cellular hubs essential for neoangiogenesis of certain aggressive adenocarcinomas and metastatic transition but not adenomas. Proc Natl Acad Sci: USA. 26, 105, 2008. 　　 30. Nishikii H, Eto K, Tamura N, Hattori K, Heissig B, Kanaji T, Sawaguchi A, Goto S, Ware J, Nakauchi H. Metalloproteinase regulation improves in vitro generation of efficacious platelets from mouse embryonic stem cells. J Exp Med.: 205, 1917-27, 2008. IF 10.790/CI 80 31. Heissig B, Lund LR, Akiyama H, Ohki M, Morita Y, Rømer J, Nakauchi H, Okumura K, Ogawa H, Werb Z, Danø K, Hattori K. The plasminogen fibrinolytic pathway is required for hematopoietic regeneration. Cell Stem Cell: 1, 658–670, 2007. 32. Kiaei M, Kipiani K, Calingasan NY, Wille E, Chen J, Heissig B, Rafii S, Lorenzl S, Flint Beal M. Matrix metalloproteinase-9 regulates TNF-alpha and FasL expression in neuronal, glial cells and its absence extends life in a transgenic mouse model of amyotrophic lateral sclerosis. Exp. Neurol.: 205, 74-81, 2007. 33. Jin DK, Shido K, Kopp H-G, Petit I, Shmelkov V, Young LM, Hooper AT, Amano H, Avecilla ST, Heissig B, Hattori K, Zhang F, Hicklin DJ, Wu Y, Zhu Z, Dunn A, Salari H, Werb Z, Hackett NR, Crystal RG, Lyden D, Rafii S. Cytokine-mediated deployment of SDF-1 induces revascularization through recruitment of CXCR4+ hemangiocytes. Nature Medicine: 12, 557-97, 2006. 34. Fietz T, Hattori K, Thiel E, Heissig B. Increased soluble urokinase plasminogen activator receptor (suPAR) serum levels after granulocyte colony-stimulating factor treatment do not predict successful progenitor cell mobilization in vivo. Blood: 107, 3408-9, 2006. 35. Heissig B, Rafii S, Akiyama H, Ohki Y, Sato Y, Rafael T, Zhu Z, Hicklin DJ, Okumura K, Ogawa H, Werb Z, Hattori K. Low-dose irradiation promotes tissue revascularisation through VEGF release from mast cells and MMP-9-mediated progenitor cell mobilization. J. Exp. Med.: 202, 739-50, 2005. i. 36. Ohki Y, Heissig B, Sato Y, Akiyama H, Zhu Z, Hicklin DJ, Shimada K, Ogawa H, Daida H, Hattori K, Ohsaka A. Granulocyte Colony-Stimulating Factor promotes neovascularization by releasing vascular endothelial growth factor from neutrophils. FASEB J, 19(14), 2005-7, 2005. 37. Avecilla ST, Hattori K, Heissig B, Tejada R, Liao F, Shido K, Jin DK, Dias S, Zhang F, Hartman TE, Hackett NR, Crystal RG, Witte L, Hicklin DJ, Bohlen P, Eaton D, Lyden D, de Sauvage F, Rafii S. Chemokine-mediated interaction of hematopoietic progenitors with the bone marrow vascular niche is required for thrombopoiesis. Nature Medicine: 10, 64-71, 2004. 38. Salven P, Hattori K, Heissig B, Rafii S. Interleukin-1alpha promotes angiogenesis in vivo via VEGFR-2 pathway by inducing inflammatory cell VEGF synthesis and secretion. FASEB J: 16, 1471-3, 2002. IF 5.595/CI 173 39. Heissig B, Hattori K,* Dias S, Friedrich M, Ferris B, Hackett NR, Crystal RG, Besmer P, Lyden D, Moore MAS, Werb Z, Rafii S. Recruitment of Stem and Progenitor cells from the bone marrow niche requires MMP-9 mediated release of kit-ligand. Cell: 109, 625-637, 2002. 40. Hattori K,* Heissig B,* Wu Yan, Dias S, Tejada R, Ferris B, Hicklin DJ, Zhu Z, Bohlen P, Witte L, Hendrikx J, Hacket NR, Crystal Ronald G., Moore MAS, Werb Z, Lyden D, Rafii S. Placental growth factor reconstitutes hematopoiesis by recruiting VEGFR1+ stem cells from bone marrow microenvironment. Nature Medicine: 8, 841-849, 2002. 41. Rafii S, Meeus S, Dias S, Hattori K, Heissig B, Shmelkov S, Rafii D, Lyden D. Contribution of marrow-derived progenitors to vascular and cardiac regeneration. Semin. Cell Dev. Biol.: 13, 61-67, 2002. 42. Lyden D, Hattori K, Dias S, Costa C, Blaikie P, Butros L, Chadburn A, Heissig B, Marks W, Witte L, Wu Y, Hicklin D, Zhu Z, Hackett Neil R., Crystal RG, Moore MAS, Hajjar KA, Manova K, Benezra R, Rafii S. Impaired recruitment of bone marrow-derived endothelial and hematopoietic precursor cells blocks tumor angiogenesis and growth. Nature Medicine: 7, 1194-201, 2001. 43. Dias S, Hattori K, Heissig B, Zhu Z, Wu Y, Witte L, Hicklin DJ, Tateno M, Bohlen P, Moore MAS, Rafii S. Inhibition of both paracrine and autocrine VEGF/VEGFR-2 signaling pathways is essential to induce long-term remission of xenotransplanted human leukemias. PNAS: 98, 10857-10862, 2001. 44. Sick C, Schultheis B, Pasternak G, Kottke I, Hoerner S, Heissig B, Hehlmann R. Predominantly BCR-ABL negative myeloid precursors in interferon-alpha treated chronic myelogenous leukemia: a follow-up study of peripheral blood colony-forming cells with fluorescence in situ hybridization. Ann. Hematol.: 80, 9-16, 2001. 45. Hattori K, Dias S, Heissig B, Hackett Neil R., Lyden D, Tateno M, Hicklin DJ, Zhu Z, Witte L, Crystal RG, Moore MAS, Rafii S. Vascular endothelial growth factor and angiopoietin-1 stimulate postnatal hematopoiesis by recruitment of vasculogenic and hematopoietic stem cells. J. Exp. Med: 193,1005-1014, 2001. 46. Hattori K, Heissig B, Tashiro K, Honjo T, Tateno M, Shieh J-J, Hackett NR, Quitoriano MS, Crystal RG, Rafii S, Moore MAS. Plasma elevation of stromal cell-derived factor-1 induces mobilization of mature and immature hematopoietic progenitor and stem cells. Blood: 97, 3354-3360, 2001. 47. Schultheis B, Heissig B, Pasternak G, Hörner S, Hehlmann R. Interferon-alpha-treated patients with chronic myelogenous leukemia show BCR/ABL-positive peripheral blood progenitor cells surviving long-term culture. Folia Biol. 46, 251-255, 2000. 48. Lane WJ, Dias S, Hattori K, Heissig B, Choy M, Lam G, Moore MAS, Rafii S. Stromal-derived factor-induced megakaryocyte migration and platelet production is dependent on matrix metalloproteinases. Blood: 96, 4152-4159, 2000. 49. Dias S, Hattori K, Zhu Z, Heissig B, Choy M, Lane W, Wu Y, Chadburn A, Hyjek E, Gill M, Hicklin DJ, Witte L, Moore MAS, Rafii S. Autocrine stimulation of VEGF-R2 activates human leukemic cell growth and migration. J. Clin. Inv.: 106, 511-521, 2000. 50. Heissig B, Pasternak G, Hoerner S, Schwerdtfeger R, Rossol S, Hehlmann R. CD14+ peripheral blood mononuclear cells from chronic myelogenous leukemia and normal donors are inhibitory to short- and long-term cultured colony-forming cells. Leuk. Research: 24, 217-31, 2000.

研究テーマ

Role of proteases in normal development and disease

研究業績（論文）

1. Salama Y, Munakata S, Osada T, Takahashi S, Hattori K, Heissig B. Heparin-binding EGF-like growth factor via miR-126 controls tumor formation/growth and the proteolytic niche in murine models of colorectal and colitis-associated cancers. Cell Death & Disease. doi: 10.1038/s41419-024-07126-2, 2024.

2. Skrypnyk M, Yatsenko T, Riabets O, Salama Y, Skikevych M, Osada T, Tobita M, Takahashi S, Hattori K, Heissig B. Heliyon. 29;10(11):e31777. doi: 10.1016/j.heliyon..e31777. eCollection 5, 2024.

3. Yatsenko T, Rios R, Nogueira T, Salama Y, Takahashi S, Adachi E, Tabe Y, Hattori N, Osada T, Naito T, Takahashi K, Hattori K, Heissig B. The influence of 4G/5G polymorphism in the plasminogen-activator-inhibitor-1 promoter on COVID-19 severity and endothelial dysfunction. Front. Immunol., Sec. Inflammation, Volume 15 - doi.org/10.3389/fimmu.2024.1445294 30 August, 2024.

4. Yatsenko T, Rios R, Nogueira T, Salama Y, Takahashi S, Tabe Y, Naito T, Takahashi K, Hattori K, Heissig B. Urokinase-type plasminogen activator and plasminogen activator inhibitor-1 complex as a serum biomarker for COVID-19. Front Immunol. 2024 Jan 11:14:1299792.; Front Immunol. Jan, 2024.11:14:1299792. doi: 10.3389/fimmu.2024.1390698./Corrigendum Front Immunol 2024 Jan 11:14:1299792; Front Immunol.Jan 11:14:1299792;doi: 10.3389/fimmu.2023.1299792, 2024.

5. Mizoue Y, Ikeda T, Ikegami T, Riabets O, Oishi Y, Tobita M, Akutsu H, Hattori K, Heissig B, Koide K. The stem cell transcription factor ZEP296 transforms NIH3T3 cells and promotes anchorage-independent growth of cancer cells. Int J Dev Biol.67(4):147-153. doi: 10.1387/ijdb.230143hk, 2023.

6. Salama Y, Takahashi S, Tsuda Y, Okada Y, Hattori K, and Heissig B. YO2 induces melanoma cell apoptosis through p53-mediated LRP1 downregulation. Cancers 15, 288; doi 10.3390/cancers15010288, 2023.

7. Heissig B, Salama Y, Iakoubov R, Vehreschild JJ, Rios R, Nogueira T, Maria J.G.T. Vehreschild M.J.G.T., Stecher M, Mori H, Lanznaster J, Adachi E, Jakob C, Tabe Y, Ruethrich M, Borgmann S, Naito T, Wille K, Valenti S, Hower M, Hattori N, Rieg S, Nagaoka T, Jensen BE, Yotsuyanagi H, Hertenstein B, Ogawa H, Wyen C, Kominami E, Roemmele C, Takahashi S, Rupp J, Takahashi K, Hanses F, Hattori K and on behalf of the LEOSS study group. COVID-19 Severity and Thrombo-Inflammatory Response Linked to Ethnicity. Biomedicines, 10(10), 2549; doi.org/10.3390/biomedicines10102549, 2022.

8. Heissig B*, Salama Y*, Tateno M, Takahashi S, Hattori K. siRNA against CD40 delivered via a fungal recognition receptor ameliorates murine acute graft-versus-host disease. eJHaem, Volume 3, Issue3, doi.org/10.1002/jha2.439, 2022.

9. Salama Y, Jaradat N, Hattori K, Heissig B. Aloysia Citrodora Essential Oil Inhibits Melanoma Cell Growth and Migration by Targeting HB-EGF-EGFR Signaling. Int J Mol Sci. Jul 29;22(15):8151,2021. doi: 10.3390/ijms22158151, 2021.

10. Salama Y, Hendrik Heida A, Yokoyama K, Takahashi S, Hattori K, Heissig B. The EGFL7-ITGB3-KLF2 axis enhances myeloma cell survival and contributes to drug resistance. Blood Advances, 24;4(6):1021-1037, 2020.

11. Sato-Okabayashi Y, Isoda K, Heissig B, Kadoguchib T, Akita K, Kitamura K, Shimada K, Hattori K, Daida H. Low-dose oral cyclophosphamide therapy reduces atherosclerosis progression by decreasing inflammatory cells in a murine model of atherosclerosis. Int J Cardiol Heart Vasc. May 10; 28:100529, 2020.

12. Salama Y, Lin SY, Dhahri D, Hattori K, Heissig B. The fibrinolytic factor tPA drives LRP1-mediated melanoma growth and metastasis. FASEB J: 33(3):3465-3480, 2019.

13. Honjo K, Munakata S, Tashiro Y, Salama Y, Shimazu H, Eiamboonsert S, Dhahri D, Ichimura A, Dan T, Miyata T, Takeda K, Sakamoto K, Hattori K, Heissig B. Plasminogen activator inhibitor-1 regulates macrophage-dependent postoperative adhesion by enhancing EGF-HER1 signaling in mice. FASEB J: Jun;31(6):2625-2637, 2017.

14. Shimazu H, Munakata S, Tashiro Y, Salama Y, Dhahri D, Eiamboonsert S, Ota Y, Onoda H, Tsuda Y, Okada Y, Nakauchi H, Heissig B, Hattori K. Pharmacological targeting of plasmin prevents lethality and tissue damage in a murine model of macrophage activation syndrome. Blood: 6;130(1):59-72, 2017.

15. Eiamboonsert S, Salama Y, Watarai H, Dhahri D, Tsuda Y, Okada Y, Hattori K, Heissig B. The role of plasmin in the pathogenesis of murine multiple myeloma. Biochem Biophys Res Commun.: 24:488(2):387-392, 2017.

16. Salama Y, Hattori K, Heissig B. The angiogenic factor Egfl7 alters thymogenesis by activating Flt3 signaling. Biochem Biophys Res Commun.: 19,490(2):209-216, 2017.

17. Dhahri D, Sato-Kusubata K, Ohki-Koizumi Mo, Nishida C, Tashiro Y, Munakata S, Shimazu H, Salama Y, Eiamboonsert S, Nakauchi H, Hattori K#, Heissig B#. Fibrinolytic crosstalk with endothelial cells expands murine mesenchymal stromal cells. Blood: 128(8), 1063-75, 2016.　

18. Munakata S*, Tashiro Y*, Nishida C, Sato A, Komiyama H, Shimazu H, Dhahri D, Salama Y, Eiamboonsert S, Takeda K, Yagita H, Tsuda Y, Okada Y, Nakauchi H, Sakamoto K, Heissig B#, Hattori K#. Inhibition of Plasmin Protects Against Colitis in Mice by Suppressing Matrix Metalloproteinase 9-mediated Cytokine Release from Myeloid Cells. Gastroenterology: 148(3), 565-578, 2015.

19. Sato A, Nishida C, Sato-Kusubata K, Ishihara M, Tashiro Y, Gritli I, Shimazu H, Munakata S, Yagita H, Okumura K, Tsuda Y, Okada Y, Tojo A, Nakauchi, H, Takahashi S, Heissig B#, Hattori K#. Inhibition of plasmin attenuates murine acute graft-versus-host disease mortality by suppressing the matrix metalloproteinase-9-dependent inflammatory cytokine storm and effector cell trafficking. Leukemia: 29(1), 145-56, 2015.

20. Nakahara F, Kitaura J, Uchida T, Nishida C, Togami K, Inoue D, Matsukawa T, Kagiyama Y, Enomoto Y, Kawabata K C., Chen-Yi L, Komeno Y, Izawa K, Oki T, Nagae G, Harada Y, Harada H, Otsu M, Aburatani H, Heissig B, Hattori K, Kitamura T. Hes1 promotes blast crisis in chronic myelogenous leukemia through MMP-9 upregulation in leukemic cells. Blood: 123(25), 3932-42, 2014.

21. Caiado F, Carvalho T, Rosa I, Remedio L, Costa A, Matos J, Heissig B, Yagita H, Hattori K, da Silva JP, Fidalgo P, Pereira AD, Dias S. Bone Marrow-Derived CD11b+Jagged2+ Cells promote epithelial-to-mesenchymal transition and metastasization in colorectal cancer. Cancer Res.: 73, 4233-4246, 2013.

22. Tashiro Y, Nishida C, Sato-Kusubata K, Ohki-Koizumi M, Ishihara M, Sato A, Gritli I, Komiyama H, Sato Y, Dan T, Miyata T, Okumura K, Tomiki Y, Sakamoto K, Nakauchi H, Heissig B#, Hattori K#. Inhibition of PAI-1 induces neutrophil-driven neoangiogenesis and promotes tissue regeneration via production of angiocrine factors in mice. Blood: 119, 6382-93, 2012.

23. Nishida C, Kusubata K, Tashiro Y, Gritli I, Sato A, Ohki-Koizumi M, Morita Y, Nagano M, Sakamoto T, Koshikawa N, Kuchimaru T, Kizaka-Kondoh S, Seiki M, Nakauchi H, Heissig B#, Hattori K#. MT1-MMP plays a critical role in hematopoiesis by regulating HIF-mediated chemokine-/cytokine gene transcription within niche cells. Blood: 119, 5405-16, 2012.

24. Okaji Y, Tashiro Y, Gritli I, Nishida C, Sato A, Ueno Y, Del Canto Gonzalez S, Ohki-Koizumi M, Akiyama H, Nakauchi, Hattori K#, Heissig B#. Plasminogen deficiency attenuates post-natal erythropoiesis in male C57BL/6 mice through decreased activity of the LH-testosterone axis. Exp. Hematology: 40: 143-154, 2012.

25. Ishihara M, Nishida C, Tashiro Y, Gritli I, Rosenkvist J, Koizumi M, Okaji Y, Yamamoto R, Yagita H, Okumura K, Nishikori M, Wanaka K, Tsuda Y, Okada Y, Nakauchi H, Heissig B#, Hattori K#. Plasmin inhibitor reduces lymphoid tumor growth by suppressing matrix metalloproteinase-9 dependent CD11b+/F4/80+ myeloid cell recruitment. Leukemia: 26, 332–339, 2012.

26. Piao JH, Hasegawa M, Heissig B, Hattori K, Takeda K, Iwakura Y, Okumura K, Inohara N, Nakano H. Tumor necrosis factor receptor-associated factor (Traf)2 controls homeostasis of the colon to prevent spontaneous development of murine inflammatory bowel disease. J Biol Chem: 286, 17879-88, 2011.

27. Ohki M*, Ohki Y*, Ishihara M, Nishida C, Tashiro Y, Akiyama H, Komiyama H, Lund LR, Nitta A, Yamada K, Zhu Z, Ogawa H, Yagita H, Okumura K, Nakauchi H, Werb Z, Heissig #, Hattori K#. Tissue type plasminogen activator regulates myeloid-cell dependent neoangiogenesis during tissue regeneration. Blood: 115, 4302-4312, 2010.

28. Sato Y, Ohki Y, Akiyama H, Rosenkvist J, Gritli I, Okumura K, Ogawa H, Daida H, Heissig B, Hattori K, Ohsaka A. Targeted deletion of matrix metalloproteinase-9 reduces neutrophil accumulation during G-CSF-induced neoangiogenesis. Cytometry Research: 19(2), 53-62, 2009.

29. Kerbel RS, Benezra R, Lyden DC, Hattori K, Heissig B, Nolan DJ, Mittal V, Shaked Y, Dias S, Bertolini F, Rafii S. Endothelial progenitor cells are cellular hubs essential for neoangiogenesis of certain aggressive adenocarcinomas and metastatic transition but not adenomas. Proc Natl Acad Sci: USA. 26, 105, 2008. 　　

30. Nishikii H, Eto K, Tamura N, Hattori K, Heissig B, Kanaji T, Sawaguchi A, Goto S, Ware J, Nakauchi H. Metalloproteinase regulation improves in vitro generation of efficacious platelets from mouse embryonic stem cells. J Exp Med.: 205, 1917-27, 2008. IF 10.790/CI 80

31. Heissig B, Lund LR, Akiyama H, Ohki M, Morita Y, Rømer J, Nakauchi H, Okumura K, Ogawa H, Werb Z, Danø K, Hattori K. The plasminogen fibrinolytic pathway is required for hematopoietic regeneration. Cell Stem Cell: 1, 658–670, 2007.

32. Kiaei M, Kipiani K, Calingasan NY, Wille E, Chen J, Heissig B, Rafii S, Lorenzl S, Flint Beal M. Matrix metalloproteinase-9 regulates TNF-alpha and FasL expression in neuronal, glial cells and its absence extends life in a transgenic mouse model of amyotrophic lateral sclerosis. Exp. Neurol.: 205, 74-81, 2007.

33. Jin DK, Shido K, Kopp H-G, Petit I, Shmelkov V, Young LM, Hooper AT, Amano H, Avecilla ST, Heissig B, Hattori K, Zhang F, Hicklin DJ, Wu Y, Zhu Z, Dunn A, Salari H, Werb Z, Hackett NR, Crystal RG, Lyden D, Rafii S. Cytokine-mediated deployment of SDF-1 induces revascularization through recruitment of CXCR4+ hemangiocytes. Nature Medicine: 12, 557-97, 2006.

34. Fietz T, Hattori K, Thiel E, Heissig B. Increased soluble urokinase plasminogen activator receptor (suPAR) serum levels after granulocyte colony-stimulating factor treatment do not predict successful progenitor cell mobilization in vivo. Blood: 107, 3408-9, 2006.

35. Heissig B, Rafii S, Akiyama H, Ohki Y, Sato Y, Rafael T, Zhu Z, Hicklin DJ, Okumura K, Ogawa H, Werb Z, Hattori K. Low-dose irradiation promotes tissue revascularisation through VEGF release from mast cells and MMP-9-mediated progenitor cell mobilization. J. Exp. Med.: 202, 739-50, 2005.
i.

36. Ohki Y, Heissig B, Sato Y, Akiyama H, Zhu Z, Hicklin DJ, Shimada K, Ogawa H, Daida H, Hattori K, Ohsaka A. Granulocyte Colony-Stimulating Factor promotes neovascularization by releasing vascular endothelial growth factor from neutrophils. FASEB J, 19(14), 2005-7, 2005.

37. Avecilla ST*, Hattori K*, Heissig B*, Tejada R, Liao F, Shido K, Jin DK, Dias S, Zhang F, Hartman TE, Hackett NR, Crystal RG, Witte L, Hicklin DJ, Bohlen P, Eaton D, Lyden D, de Sauvage F, Rafii S. Chemokine-mediated interaction of hematopoietic progenitors with the bone marrow vascular niche is required for thrombopoiesis. Nature Medicine: 10, 64-71, 2004.

38. Salven P, Hattori K, Heissig B, Rafii S. Interleukin-1alpha promotes angiogenesis in vivo via VEGFR-2 pathway by inducing inflammatory cell VEGF synthesis and secretion. FASEB J: 16, 1471-3, 2002. IF 5.595/CI 173

39. Heissig B,* Hattori K,* Dias S, Friedrich M, Ferris B, Hackett NR, Crystal RG, Besmer P, Lyden D, Moore MAS, Werb Z, Rafii S. Recruitment of Stem and Progenitor cells from the bone marrow niche requires MMP-9 mediated release of kit-ligand. Cell: 109, 625-637, 2002.

40. Hattori K,* Heissig B,* Wu Yan, Dias S, Tejada R, Ferris B, Hicklin DJ, Zhu Z, Bohlen P, Witte L, Hendrikx J, Hacket NR, Crystal Ronald G., Moore MAS, Werb Z, Lyden D, Rafii S. Placental growth factor reconstitutes hematopoiesis by recruiting VEGFR1+ stem cells from bone marrow microenvironment. Nature Medicine: 8, 841-849, 2002.

41. Rafii S, Meeus S, Dias S, Hattori K, Heissig B, Shmelkov S, Rafii D, Lyden D. Contribution of marrow-derived progenitors to vascular and cardiac regeneration. Semin. Cell Dev. Biol.: 13, 61-67, 2002.

42. Lyden D, Hattori K, Dias S, Costa C, Blaikie P, Butros L, Chadburn A, Heissig B, Marks W, Witte L, Wu Y, Hicklin D, Zhu Z, Hackett Neil R., Crystal RG, Moore MAS, Hajjar KA, Manova K, Benezra R, Rafii S. Impaired recruitment of bone marrow-derived endothelial and hematopoietic precursor cells blocks tumor angiogenesis and growth. Nature Medicine: 7, 1194-201, 2001.

43. Dias S, Hattori K, Heissig B, Zhu Z, Wu Y, Witte L, Hicklin DJ, Tateno M, Bohlen P, Moore MAS, Rafii S. Inhibition of both paracrine and autocrine VEGF/VEGFR-2 signaling pathways is essential to induce long-term remission of xenotransplanted human leukemias. PNAS: 98, 10857-10862, 2001.

44. Sick C, Schultheis B, Pasternak G, Kottke I, Hoerner S, Heissig B, Hehlmann R. Predominantly BCR-ABL negative myeloid precursors in interferon-alpha treated chronic myelogenous leukemia: a follow-up study of peripheral blood colony-forming cells with fluorescence in situ hybridization. Ann. Hematol.: 80, 9-16, 2001.

45. Hattori K, Dias S, Heissig B, Hackett Neil R., Lyden D, Tateno M, Hicklin DJ, Zhu Z, Witte L, Crystal RG, Moore MAS, Rafii S. Vascular endothelial growth factor and angiopoietin-1 stimulate postnatal hematopoiesis by recruitment of vasculogenic and hematopoietic stem cells. J. Exp. Med: 193,1005-1014, 2001.

46. Hattori K, Heissig B, Tashiro K, Honjo T, Tateno M, Shieh J-J, Hackett NR, Quitoriano MS, Crystal RG, Rafii S, Moore MAS. Plasma elevation of stromal cell-derived factor-1 induces mobilization of mature and immature hematopoietic progenitor and stem cells. Blood: 97, 3354-3360, 2001.

47. Schultheis B, Heissig B, Pasternak G, Hörner S, Hehlmann R. Interferon-alpha-treated patients with chronic myelogenous leukemia show BCR/ABL-positive peripheral blood progenitor cells surviving long-term culture. Folia Biol. 46, 251-255, 2000.

48. Lane WJ, Dias S, Hattori K, Heissig B, Choy M, Lam G, Moore MAS, Rafii S. Stromal-derived factor-induced megakaryocyte migration and platelet production is dependent on matrix metalloproteinases. Blood: 96, 4152-4159, 2000.

49. Dias S, Hattori K, Zhu Z, Heissig B, Choy M, Lane W, Wu Y, Chadburn A, Hyjek E, Gill M, Hicklin DJ, Witte L, Moore MAS, Rafii S. Autocrine stimulation of VEGF-R2 activates human leukemic cell growth and migration. J. Clin. Inv.: 106, 511-521, 2000.

50. Heissig B, Pasternak G, Hoerner S, Schwerdtfeger R, Rossol S, Hehlmann R. CD14+ peripheral blood mononuclear cells from chronic myelogenous leukemia and normal donors are inhibitory to short- and long-term cultured colony-forming cells. Leuk. Research: 24, 217-31, 2000.

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