Biochemistry

1984-1988

Graduate student, Kyushu University Graduate School of Medicine（Discovery of the growth factor midkine）

1988-

Research associate, Kagoshima University Faculty of Medicine（Analysis of the biological functions of midkine, particularly in cancer）

1993-

Research associate, Assistant professor, Associate professor, Nagoya University Graduate School of Medicine（Application of midkine to clinical use, particularly for cardiovascular disease, carcinomas and inflammatory diseases; Discovery of the critical roles of basigin in genesis of the retina and sex organ; Discovery of the biological roles of keratan sulfate in inhibition of neuronal axon regeneration）

2004-

Professor, Nagoya University Graduate School of Medicine

Carcinogenesis and remodeling after neuronal injury

We will perform 2 research projects. 1. Analysis of carcinogenesis of neuroblastoma: Neuroblastoma is the most common solid tumor in childhood. Particularly patients with tumors bearing MYCN amplification show poor prognosis. Using MYCN Tg mice, we have identified precancerous lesions during an early phase of carcinogenesis. We will analyze molecular events which occur during early carcinogenesis of neuroblastoma. 2. Analysis of remodeling after neuronal injury: Among inhibitory factors of axonal regeneration after neuronal injury, chondroitin sulfate has been recently highlighted. We have found the importance of keratan sulfate in axonal regeneration inhibition after neuronal injury. We will address many questions regarding mechanisms of the inhibition of axonal regeneration.

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1. Ishimoto T et al. Downregulation of monocyte chemoattractant protein-1 involving short interfering RNA attenuates Hapten-induced contact hypersensitivity. Mol. Ther. 16: 387-395 (2008)
2. Takei Y et al. In vivo silencing of a molecular target by short interfering RNA electroporation: Tumor vascularization correlates to delivery efficiency. Mol. Cancer Ther. 7: 211-221 (2008)
3. Kosugi T et al. Midkine is involved in tubulo-interstitial inflammation associated with diabetic nephropathy. Lab. Invest. 87: 903-913 (2007)
4. Chen S et al. Midkine and LDL receptor-related protein 1 contribute to the anchorage-independent cell growth of cancer cells. J. Cell Sci. 120: 4009-4015 (2007)
5. Horiba M et al. Midkine plays a protective role against cardiac ischemia/reperfusion injury through a reduction of apoptotic reaction. Circulation 114: 1713-1720 (2006)
6. Zhang H et al. N-acetylglucosamine 6-O-sulfotransferase-1 is required for brain keratan sulfate biosynthesis and glial scar formation after brain injury. Glycobiology 16: 702-710 (2006)
7. Kawashima H et al. N-Acetylglucosamine-6-O-sulfotransferase-1 and -2 cooperatively control lymphocyte homing through L-selectin ligand biosynthesis in high endothelial venules. Nat. Immunol. 6: 1096-1104 (2005)
8. Takei Y et al. A small interfering RNA targeting vascular endothelial growth factor as cancer therapeutics. Cancer Res. 64: 3365-3370 (2004)
9. Uchimura K et al. N-acetylglucosamine 6-O-sulfotransferase-1 regulates expression of L-selectin ligands and lymphocyte homing. J. Biol. Chem. 279: 35001-35008 (2004)
10. Suzuki N et al. Proteasomal degradation of the nuclear targeting growth factor midkine. J. Biol. Chem. 279: 17785-17791 (2004)
11. Shibata Y et al. Nuclear targeting by the growth factor midkine. Mol. Cell. Biol. 22: 6788-6796 (2002)
12. Takei Y et al. Antisense oligonucleotide targeted to midkine, a heparin-binding growth factor, suppresses tumorigenicity of mouse rectal carcinoma cells. Cancer Res. 61: 8486-8491 (2001)
13. Sato W et al. Midkine is involved in neutrophil infiltration into the tubulointerstitium in ischemic renal injury. J. Immunol. 167: 3463-3469 (2001)
14. Qi M et al. Haptotactic migration induced by midkine: Involvement of protein-tyrosine phosphatase ζ, mitogen-activated protein kinase and phosphatidylinositol 3-kinase. J. Biol. Chem. 276: 15868-15875 (2001)
15. Ishiguro K et al. Complete antithrombin deficiency in mice results in embryonic lethality. J. Clin. Invest. 106: 873-878 (2000)
16. Horiba M et al. Neointima formation in a restenosis model is suppressed in midkine-deficient mice. J. Clin. Invest. 105: 489-495 (2000)
17. Uchimura K et al. Molecular cloning and characterization of an N-acetylglucosamine-6-O-sulfotransferase. J. Biol. Chem. 273: 22577-22583 (1998)
18. Kadomatsu K et al. Expression of sulfated glycoprotein 2 is associated with carcinogenesis induced by N-nitroso-N-methylurea in rat prostate and seminal vesicle. Cancer Res. 53: 1480-1483 (1993)
19. Tsutsui J et al. A new family of heparin-binding growth differentiation factors: Increased midkine expression in Wilms' tumor and other human carcinomas. Cancer Res. 53: 1281-1285 (1993)
20. Kadomatsu K et al. A retinoic acid responsive gene, MK, found in the teratocarcinoma system is expressed in spatially and temporally controlled manner during mouse embyogenesis. J. Cell Biol. 110: 607-616 (1990)

Young Investigator Award of Japanese Biochemical Society (1997)