Angiogenesis, formation of new blood vessels, is a pivotal process in organogenesis and tissue regeneration, requiring ordered endothelial cell proliferation, migration, and homotypic and heterotypic intercellular adhesion. However, when angiogenesis is induced (and unregulated) in pathological conditions, it greatly contributes to the progression of disease, including cancer, diabetes, ischemic, and inflammatory disorders. Thus, definition of the intrinsic molecular controls that regulate angiogenic vessel growth promises novel therapeutic approaches for angiogenesis-associated diseases. In the recent decades, investigators have identified various endothelial cell surface receptors and their activating ligands that promote and coordinate angiogenic vessel formation. However, much less is known about the endothelial receptors that transduce "anti-angiogenic (or angiostatic)" signals, though they could be used for angiogenesis inhibition. CD148 (DEP-1/PTPeta) is a transmembrane tyrosine phosphatase which is abundantly expressed in vascular endothelial cells of various tissues. We have shown that CD148 suppresses endothelial growth factor signals and strongly inhibits endothelial cell growth in culture and in vivo. Further, we have recently found that thrombospondin-1 (TSP-1) serves as an agonistic ligand for CD148. We are currently determining: 1. the role of CD148 in postnatal angiogenesis (physiological and pathological); 2. the role of TSP-1 and CD148 interaction in angiogenesis. These efforts should explore new pathways of angiogenesis inhibition and provide a novel strategy for anti-angiogenesis therapy. Another project in the lab examines the mechanisms of diabetic renal microvascular injury. We found that loss of eNOS or SOD enzyme largely exacerbates diabetic glomerular microvascular injury in mice. The lab examines the detailed mechanisms of this using conditional as well as global knockout mouse. Last, as a primary lab of Vanderbilt O'Brien Mouse Kidney Physiology and Disease Center (MKPDC), the lab and VUIIS scientists are developing non-invasive kidney imaging techniques that enable structural, functional, and molecular assessments of mouse kidney disease in living animals.


The following timeline graph is generated from all co-authored publications.

Featured publications are shown below:

  1. Assessment of unilateral ureter obstruction with multi-parametric MRI. Wang F, Takahashi K, Li H, Zu Z, Li K, Xu J, Harris RC, Takahashi T, Gore JC (2018) Magn Reson Med 79(4): 2216-2227
    › Primary publication · 28736875 (PubMed) · PMC5870889 (PubMed Central)
  2. Expression of receptor-type protein tyrosine phosphatase in developing and adult renal vasculature. Takahashi K, Kim R, Lauhan C, Park Y, Nguyen NG, Vestweber D, Dominguez MG, Valenzuela DM, Murphy AJ, Yancopoulos GD, Gale NW, Takahashi T (2017) PLoS One 12(5): e0177192
    › Primary publication · 28542220 (PubMed) · PMC5444631 (PubMed Central)
  3. Determination of the CD148-Interacting Region in Thrombospondin-1. Takahashi K, Sumarriva K, Kim R, Jiang R, Brantley-Sieders DM, Chen J, Mernaugh RL, Takahashi T (2016) PLoS One 11(5): e0154916
    › Primary publication · 27149518 (PubMed) · PMC4858292 (PubMed Central)
  4. Novel methods for microCT-based analyses of vasculature in the renal cortex reveal a loss of perfusable arterioles and glomeruli in eNOS-/- mice. Perrien DS, Saleh MA, Takahashi K, Madhur MS, Harrison DG, Harris RC, Takahashi T (2016) BMC Nephrol : 24
    › Primary publication · 26936597 (PubMed) · PMC4776352 (PubMed Central)
  5. Mapping murine diabetic kidney disease using chemical exchange saturation transfer MRI. Wang F, Kopylov D, Zu Z, Takahashi K, Wang S, Quarles CC, Gore JC, Harris RC, Takahashi T (2016) Magn Reson Med 76(5): 1531-1541
    › Primary publication · 26608660 (PubMed) · PMC4882276 (PubMed Central)
  6. Renal Denervation Prevents Immune Cell Activation and Renal Inflammation in Angiotensin II-Induced Hypertension. Xiao L, Kirabo A, Wu J, Saleh MA, Zhu L, Wang F, Takahashi T, Loperena R, Foss JD, Mernaugh RL, Chen W, Roberts J, Osborn JW, Itani HA, Harrison DG (2015) Circ Res 117(6): 547-57
    › Primary publication · 26156232 (PubMed) · PMC4629828 (PubMed Central)
  7. Current MRI techniques for the assessment of renal disease. Takahashi T, Wang F, Quarles CC (2015) Curr Opin Nephrol Hypertens 24(3): 217-23
    › Primary publication · 26066472 (PubMed) · PMC4467464 (PubMed Central)
  8. CD148 tyrosine phosphatase promotes cadherin cell adhesion. Takahashi K, Matafonov A, Sumarriva K, Ito H, Lauhan C, Zemel D, Tsuboi N, Chen J, Reynolds A, Takahashi T (2014) PLoS One 9(11): e112753
    › Primary publication · 25386896 (PubMed) · PMC4227875 (PubMed Central)
  9. Role of endothelial nitric oxide synthase in diabetic nephropathy: lessons from diabetic eNOS knockout mice. Takahashi T, Harris RC (2014) J Diabetes Res : 590541
    › Primary publication · 25371905 (PubMed) · PMC4211249 (PubMed Central)
  10. Longitudinal assessment of mouse renal injury using high-resolution anatomic and magnetization transfer MR imaging. Wang F, Jiang R, Takahashi K, Gore J, Harris RC, Takahashi T, Quarles CC (2014) Magn Reson Imaging 32(9): 1125-32
    › Primary publication · 25093632 (PubMed) · PMC4171209 (PubMed Central)
  11. Repeatability and sensitivity of high resolution blood volume mapping in mouse kidney disease. Wang F, Jiang RT, Tantawy MN, Borza DB, Takahashi K, Gore JC, Harris RC, Takahashi T, Quarles CC (2014) J Magn Reson Imaging 39(4): 866-71
    › Primary publication · 24006202 (PubMed) · PMC3858530 (PubMed Central)
  12. Pancreatic islet vasculature adapts to insulin resistance through dilation and not angiogenesis. Dai C, Brissova M, Reinert RB, Nyman L, Liu EH, Thompson C, Shostak A, Shiota M, Takahashi T, Powers AC (2013) Diabetes 62(12): 4144-53
    › Primary publication · 23630302 (PubMed) · PMC3837044 (PubMed Central)
  13. Diagnostic biomarkers of diabetic nephropathy. Ito H, Fujita H, Takahashi T (2008) Expert Opin Med Diagn 2(2): 161-9
    › Primary publication · 23485136 (PubMed)
  14. Assessment of renal function in mice with unilateral ureteral obstruction using 99mTc-MAG3 dynamic scintigraphy. Tantawy MN, Jiang R, Wang F, Takahashi K, Peterson TE, Zemel D, Hao CM, Fujita H, Harris RC, Quarles CC, Takahashi T (2012) BMC Nephrol : 168
    › Primary publication · 23228112 (PubMed) · PMC3542003 (PubMed Central)
  15. SOD1, but not SOD3, deficiency accelerates diabetic renal injury in C57BL/6-Ins2(Akita) diabetic mice. Fujita H, Fujishima H, Takahashi K, Sato T, Shimizu T, Morii T, Shimizu T, Shirasawa T, Qi Z, Breyer MD, Harris RC, Yamada Y, Takahashi T (2012) Metabolism 61(12): 1714-24
    › Primary publication · 22632894 (PubMed) · PMC4360989 (PubMed Central)
  16. Generation of a conditional allele for the mouse endothelial nitric oxide synthase gene. Jiang R, Wang S, Takahashi K, Fujita H, Fruci CR, Breyer MD, Harris RC, Takahashi T (2012) Genesis 50(9): 685-92
    › Primary publication · 22467476 (PubMed) · PMC3399989 (PubMed Central)
  17. Thrombospondin-1 acts as a ligand for CD148 tyrosine phosphatase. Takahashi K, Mernaugh RL, Friedman DB, Weller R, Tsuboi N, Yamashita H, Quaranta V, Takahashi T (2012) Proc Natl Acad Sci U S A 109(6): 1985-90
    › Primary publication · 22308318 (PubMed) · PMC3277540 (PubMed Central)
  18. Role of blood pressure and the renin-angiotensin system in development of diabetic nephropathy (DN) in eNOS-/- db/db mice. Zhang MZ, Wang S, Yang S, Yang H, Fan X, Takahashi T, Harris RC (2012) Am J Physiol Renal Physiol 302(4): F433-8
    › Primary publication · 22114203 (PubMed) · PMC3289417 (PubMed Central)
  19. Loss of parietal cell superoxide dismutase leads to gastric oxidative stress and increased injury susceptibility in mice. Jones MK, Zhu E, Sarino EV, Padilla OR, Takahashi T, Shimizu T, Shirasawa T (2011) Am J Physiol Gastrointest Liver Physiol 301(3): G537-46
    › Primary publication · 21719741 (PubMed)
  20. High-efficiency and low-toxicity adenovirus-assisted endothelial transfection. Takahashi T, Takahashi K, Daniel TO (1999) Methods Mol Med : 307-14
    › Primary publication · 21341035 (PubMed)
  21. Microarray analysis of cellular thermotolerance. Beckham JT, Wilmink GJ, Opalenik SR, Mackanos MA, Abraham AA, Takahashi K, Contag CH, Takahashi T, Jansen ED (2010) Lasers Surg Med 42(10): 752-65
    › Primary publication · 21246580 (PubMed)
  22. Role of HSP70 in cellular thermotolerance. Beckham JT, Wilmink GJ, Mackanos MA, Takahashi K, Contag CH, Takahashi T, Jansen ED (2008) Lasers Surg Med 40(10): 704-15
    › Primary publication · 19065555 (PubMed)
  23. The tyrosine phosphatase CD148 interacts with the p85 regulatory subunit of phosphoinositide 3-kinase. Tsuboi N, Utsunomiya T, Roberts RL, Ito H, Takahashi K, Noda M, Takahashi T (2008) Biochem J 413(1): 193-200
    › Primary publication · 18348712 (PubMed)
  24. Overexpression of EPHA2 receptor destabilizes adherens junctions via a RhoA-dependent mechanism. Fang WB, Ireton RC, Zhuang G, Takahashi T, Reynolds A, Chen J (2008) J Cell Sci 121(Pt 3): 358-68
    › Primary publication · 18198190 (PubMed)
  25. Bioluminescence imaging of vascular endothelial growth factor promoter activity in murine mammary tumorigenesis. Faley SL, Takahashi K, Crooke CE, Beckham JT, Tomemori T, Shappell SB, Jansen ED, Takahashi T (2007) Mol Imaging 6(5): 331-9
    › Primary publication · 18092518 (PubMed)
  26. Deficiency of endothelial nitric-oxide synthase confers susceptibility to diabetic nephropathy in nephropathy-resistant inbred mice. Kanetsuna Y, Takahashi K, Nagata M, Gannon MA, Breyer MD, Harris RC, Takahashi T (2007) Am J Pathol 170(5): 1473-84
    › Primary publication · 17456755 (PubMed) · PMC1854944 (PubMed Central)
  27. Genetics of diabetic nephropathy: lessons from mice. Breyer MD, Tchekneva E, Qi Z, Takahashi T, Fogo AB, Zhao HJ, Harris RC (2007) Semin Nephrol 27(2): 237-47
    › Primary publication · 17418691 (PubMed)
  28. Endothelial nitric oxide synthase deficiency produces accelerated nephropathy in diabetic mice. Zhao HJ, Wang S, Cheng H, Zhang MZ, Takahashi T, Fogo AB, Breyer MD, Harris RC (2006) J Am Soc Nephrol 17(10): 2664-9
    › Primary publication · 16971655 (PubMed) · PMC4618687 (PubMed Central)
  29. Characterization of diabetic nephropathy in a transgenic model of hypoinsulinemic diabetes. Kanetsuna Y, Hirano K, Nagata M, Gannon MA, Takahashi K, Harris RC, Breyer MD, Takahashi T (2006) Am J Physiol Renal Physiol 291(6): F1315-22
    › Primary publication · 16705146 (PubMed)
  30. A monoclonal antibody against CD148, a receptor-like tyrosine phosphatase, inhibits endothelial-cell growth and angiogenesis. Takahashi T, Takahashi K, Mernaugh RL, Tsuboi N, Liu H, Daniel TO (2006) Blood 108(4): 1234-42
    › Primary publication · 16597593 (PubMed) · PMC1895872 (PubMed Central)
  31. Differential expression of the intermediate filament protein nestin during renal development and its localization in adult podocytes. Chen J, Boyle S, Zhao M, Su W, Takahashi K, Davis L, Decaestecker M, Takahashi T, Breyer MD, Hao CM (2006) J Am Soc Nephrol 17(5): 1283-91
    › Primary publication · 16571784 (PubMed)
  32. Reverse endocytosis of transmembrane ephrin-B ligands via a clathrin-mediated pathway. Parker M, Roberts R, Enriquez M, Zhao X, Takahashi T, Pat Cerretti D, Daniel T, Chen J (2004) Biochem Biophys Res Commun 323(1): 17-23
    › Primary publication · 15351694 (PubMed)
  33. Assessment of cellular response to thermal laser injury through bioluminescence imaging of heat shock protein 70. Beckham JT, Mackanos MA, Crooke C, Takahashi T, O'Connell-Rodwell C, Contag CH, Jansen ED (2004) Photochem Photobiol 79(1): 76-85
    › Primary publication · 14974719 (PubMed)
  34. A mutant receptor tyrosine phosphatase, CD148, causes defects in vascular development. Takahashi T, Takahashi K, St John PL, Fleming PA, Tomemori T, Watanabe T, Abrahamson DR, Drake CJ, Shirasawa T, Daniel TO (2003) Mol Cell Biol 23(5): 1817-31
    › Primary publication · 12588999 (PubMed) · PMC151692 (PubMed Central)
  35. Temporally compartmentalized expression of ephrin-B2 during renal glomerular development. Takahashi T, Takahashi K, Gerety S, Wang H, Anderson DJ, Daniel TO (2001) J Am Soc Nephrol 12(12): 2673-2682
    › Primary publication · 11729236 (PubMed)
  36. Vascular endothelial growth factor effects on nuclear factor-kappaB activation in hematopoietic progenitor cells. Dikov MM, Oyama T, Cheng P, Takahashi T, Takahashi K, Sepetavec T, Edwards B, Adachi Y, Nadaf S, Daniel T, Gabrilovich DI, Carbone DP (2001) Cancer Res 61(5): 2015-21
    › Primary publication · 11280761 (PubMed)
  37. 4 signaling between endothelial progenitor cells Daniel TO, Stein E, Huynh-Do U, Takahashi T (1999) J Histochem Cytochem 47(12): 1643C-1644
    › Primary publication · 10567451 (PubMed)
  38. Endothelial localization of receptor tyrosine phosphatase, ECRTP/DEP-1, in developing and mature renal vasculature. Takahashi T, Takahashi K, Mernaugh R, Drozdoff V, Sipe C, Schoecklmann H, Robert B, Abrahamson DR, Daniel TO (1999) J Am Soc Nephrol 10(10): 2135-45
    › Primary publication · 10505690 (PubMed)
  39. Renal microvascular assembly and repair: power and promise of molecular definition. Takahashi T, Huynh-Do U, Daniel TO (1998) Kidney Int 53(4): 826-35
    › Primary publication · 9551388 (PubMed)
  40. Jak3 expression in glomerular epithelia of IgA nephropathy (IgA-N) patients. Takahashi T, Shirasawa T, Miyake K, Yahagi Y, Matsumura O, Abe A, Natori Y, Yamabe H, Utsunomiya Y, Maruyama N, Mitarai T, Sakai O (1996) Clin Exp Immunol 104(3): 517-24
    › Primary publication · 9099938 (PubMed) · PMC2200441 (PubMed Central)
  41. Molecular cloning of rat JAK3, a novel member of the JAK family of protein tyrosine kinases. Takahashi T, Shirasawa T (1994) FEBS Lett 342(2): 124-8
    › Primary publication · 8143863 (PubMed)
  42. Protein tyrosine kinases expressed in glomeruli and cultured glomerular cells: Flt-1 and VEGF expression in renal mesangial cells. Takahashi T, Shirasawa T, Miyake K, Yahagi Y, Maruyama N, Kasahara N, Kawamura T, Matsumura O, Mitarai T, Sakai O (1995) Biochem Biophys Res Commun 209(1): 218-26
    › Primary publication · 7726838 (PubMed)
  43. Microlamellar structures in lobular glomerulonephritis associated with monoclonal IgG lambda paraproteinemia. A case report and review of the literature. Joh K, Aizawa S, Takahashi T, Hatakeyama M, Muto S, Asano Y, Shimizu H, Suzuki R (1990) Acta Pathol Jpn 40(12): 913-21
    › Primary publication · 2128987 (PubMed)
  44. Focal segmental glomerulosclerosis associated with infantile spasms in five mentally retarded children: a morphological analysis on mesangiolysis. Joh K, Usui N, Aizawa S, Yamaguchi Y, Chiba S, Takahashi T, Muramatsu Y, Sakai S (1991) Am J Kidney Dis 17(5): 569-77
    › Primary publication · 2024658 (PubMed)
  45. Interstitial nephritis associated with glomerulonephritis in a patient with Hashimoto's disease and idiopathic portal hypertension. Sasaki H, Joh K, Ohtsuka I, Ohta H, Ohhashi T, Hoashi S, Takahashi T, Tokuda T, Koyama K, Isogai Y (1992) Intern Med 31(5): 641-8
    › Primary publication · 1504428 (PubMed)