Takahashi, Takamune , M.D., Ph.D.
|Dept. of Medicine|
|Nephrology and Hypertension|
|Vanderbilt University School of Medicine 1161 21st Avenue South S-3223 Medical Center North Nashville TN 37232-2372|
Undergraduate School & Degree:
|M.D., Jikei University School of Medicine|
Medical School & Degree:
|Ph.D., (Medical Science), Jikei University School of Medicine|
Graduate School & Degree:
|Post Doctoral Training Vanderbilt University School of Medicine|
|Molecular Basis of Developmental and Pathological Angiogenesis.|
|Formation of vascular network is a dynamic and coordinated process that importantly supports organogenesis and tissue regeneration. It requires ordered endothelial cell differentiation, proliferation, migration, homotypic and heterotypic intercellular adhesion and morphogenesis. Further, when vessel growth is dysregulated, it has a major impact on our health and contributes to numerous malignant, ischemic and inflammatory disorders. Definition of the intrinsic molecular controls that regulate angiogenic blood vessel growth promises novel therapeutic approaches for a variety of diseases including heart disease, diabetes and cancer. |
In recent decades, the efforts identifying the angiogenic factors have identified the endothelial cell surface receptors that evoke and coordinate vessel formation. However, little is known about the functional endothelial receptors that transduce "angiostatic" signals. We have advanced the hypothesis that receptor tyrosine phosphatases (RPTPs) signal endothelial cell growth arrest upon cell-cell contacts, through juxtacrine contact with counter-receptors. We have identified CD148 (DEP-1/PTPeta) as a RPTP abundantly expressed in vascular endothelial cells. Our recent works demonstrated important roles of CD148 to: 1) arrest endothelial cell growth with cell density, 2) stabilize endothelial cell junctions, and 3) promote vascular maturation (pericyte investment).
To define the mechanism through CD148 regulates endothelial cell growth on cell-cell contacts and to know role of CD148 in postnatal angiogenesis (adaptive and pathologic), we are currently working on the projects to: 1) Map the extracellular CD148 subdomain responsible for mediating functional intermolecular associations to control CD148 activity, 2) Identify the functional ligand, 3) Define the physiological substrate and downstream signaling pathways, 4) Define the membrane receptor that associates with CD148, 5) Define the role of CD148 in postnatal angiogenic blood vessel growth (conditional knockout/transgenic experiments using inducible Cre mice). These efforts will explore a novel pathway that regulates endothelial cell growth through CD148, and will promise new strategies for anti-angiogenesis therapy. .
|Crooke CE, Faley S, Takahashi K, Faley S, Tomemori T, Shappell SB, Daniel TO, Jansen ED and Takahashi T.. In Vivo Bioluminescence Imaging of VEGF Promoter Activity in Mammary Tumorigenesis using a Transgenic Reporter Mouse. . Neoplasia (in revision)|
Nobuo Tsuboi, Tadahiko Utsunomiya, Richard L. Roberts, Masaharu Noda, Thomas O. Daniel and Takamune Takahashi.. Receptor Tyrosine Phosphatase CD148 Interacts with the p85 Regulatory Subunit and Regulates Phosphatidylinositol 3-Kinase. (submitted).
Takahashi T., Takahashi K., Liu H., Mernaugh R. and Daniel TO.. Receptor Tyrosine Phosphatase, CD148/DEP-1: An Oligomerization-Sensitive Angiostatic Switch.(submitted) .
Beckham, Joshua T, Mackanos, Mark A, Crooke, Cornelia, Takahashi, Takamune, O'Connell-Rodwell, Caitlin, Contag, Christopher H, Jansen, E Duco. Assessment of cellular response to thermal laser injury through bioluminescence imaging of heat shock protein 70. Photochem Photobiol, 79(1), 76-85, 2004
Grazia Lampugnani M, Zanetti A, Corada M, Takahashi T, Balconi G, Breviario F, Orsenigo F, Cattelino A, Kemler R, Daniel TO, Dejana E. . Contact inhibition of VEGF-induced proliferation requires vascular endothelial cadherin, beta-catenin, and the phosphatase DEP-1/CD148. . J Cell Biol., 26(161), 793-804, 2003
Takahashi T, Takahashi K, St John PL, Fleming PA, Tomemori T, Watanabe T, Abrahamson DR, Drake CJ, Shirasawa T, Daniel TO. . A mutant receptor tyrosine phosphatase, CD148, causes defects in vascular development. . Mol Cell Biol., 23(5), 1817-31, 2003
Usui J, Kurihara H, Shu Y, Tomari S, Kanemoto K, Koyama A, Sakai T, Takahashi T, Nagata M. . Localization of intercellular adherens junction protein p120 catenin during podocyte differentiation. . Anat Embryol (Berl). , 206(3), 175-84, 2003
Dikov MM, Oyama T, Cheng P, Takahashi T, Takahashi K, Sepetavec T, Edwards B, Adachi Y, Nadaf S, Daniel T, Gabrilovich DI, Carbone DP. . Vascular endothelial growth factor effects on nuclear factor-kappaB activation in hematopoietic progenitor cells. . Cancer Res., 61(5), 2015-21, 2001
Takahashi T, Takahashi K, Gerety S, Wang H, Anderson DJ, Daniel TO. . Temporally compartmentalized expression of ephrin-B2 during renal glomerular development. . J Am Soc Nephrol., 12(12), 2673-82, 2001
Takahashi T, Takahashi K, Mernaugh R, Drozdoff V, Sipe C, Schoecklmann H, Robert B, Abrahamson DR, Daniel TO. . Endothelial localization of receptor tyrosine phosphatase, ECRTP/DEP-1, in developing and mature renal vasculature. . J Am Soc Nephrol., 10(10), 2135-45, 1999
Takahashi T., Takahashi K. and Daniel TO. . High Efficiency & Low Toxicity Adenovirus- assisted Endothelial Transfection.. Methods in Molecular Medicine, Vascular Disease: Molecular Biology and Gene Therapy Protocols., 304-314, 1999
Takahashi T, Huynh-Do U, Daniel TO. . Renal microvascular assembly and repair: power and promise of molecular definition. . Kidney Int. , 53(4), 826-35, 1998
Takahashi T, Shirasawa T, Miyake K, Yahagi Y, Matsumura O, Abe A, Natori Y, Yamabe H, Utsunomiya Y, Maruyama N, Mitarai T, Sakai O. . Jak3 expression in glomerular epithelia of IgA nephropathy (IgA-N) patients. . Clin Exp Immunol., 104(3), 517-24, 1996
Park SY, Saijo K, Takahashi T, Osawa M, Arase H, Hirayama N, Miyake K, Nakauchi H, Shirasawa T, Saito T. . Developmental defects of lymphoid cells in Jak3 kinase-deficient mice. . Immunity., 3(6), 771-82, 1995
Takahashi T, Shirasawa T, Miyake K, Yahagi Y, Maruyama N, Kasahara N, Kawamura T, Matsumura O, Mitarai T, Sakai O. . Protein tyrosine kinases expressed in glomeruli and cultured glomerular cells: Flt-1 and VEGF expression in renal mesangial cells. . Biochem Biophys Res Commun., 209(1), 218-26, 1995
Takahashi T, Shirasawa T. . Molecular cloning of rat JAK3, a novel member of the JAK family of protein tyrosine kinases. . FEBS Lett., 342(2), 124-8, 1994