Research

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Michael  Klagsbrun, PhD

Michael Klagsbrun
Program:
Vascular Biology Program
Hospital Title:
Senior Associate in Medicine
Academic Title:
Patricia K. Donahoe Professor of Surgery, Harvard Medical School

Research Overview

Michael Klagsbrun has made major contributions to the field of growth factors and their receptors, particularly those that regulate the vascular system. He is credited with the first purifications of basic fibroblast growth factor (FGF-2), a potent angiogenesis factor, and of heparin-binding EGF-like growth factor (HB-EGF), a potent smooth muscle mitogen.

More recently, Dr. Klagsbrun's laboratory has purified vascular growth factor receptors. One of these, neuropilin, is a novel receptor for the angiogenesis factor, VEGF. Neuropilin was originally described as a receptor for semaphorin, a protein involved in regulating axon guidance. These studies have suggested that similar molecular mechanisms regulate angiogenesis and neuronal guidance, both of which are networking processes.

The Klagsbrun lab has demonstrated that Semaphorin 3F (SEMA3F) is a potent inhibitor of tumor angiogenesis, tumor progression and metastasis. The mechanism of SEMA3F inhibition involves rapid collapse of the F-actin cytoskeleton due to inactivation of RhoA, a small GTPase that regulates stress fiber formation. As a consequence of the cytoskeletal collapse, cell migration, a hallmark of tumor progression and metastasis, is inhibited.

Tumor-associated endothelial cells (EC) are the actual targets for anti-angiogenesis therapy. They were originally thought to be normal diploid cells. However, it is now apparent that EC are heterogeneous cell types with different functions in different organs. The Klagsbrun lab has isolated mouse EC from human tumor xenografts in mice. Unexpectedly, some tumor EC are cytogenetically abnormal and are more drug-resistant. In addition, tumor EC isolated from the TRAMP mouse model of prostate carcinoma are multi-potent and stem cell-like. They can differentiate into cartilage and bone and express EC cartilage and bone markers. In human patient samples, tumor EC are associated with calcification. Taken together, these results indicate that it may be more difficult to successfully target tumor blood vessels than originally thought.

About Michael Klagsbrun

Michael Klagsbrun received a Ph.D. in Biochemistry from the University of Wisconsin with research carried out at The Massachusetts Institute of Technology. He did his postdoctoral studies at the National Institutes of Health and was subsequently recruited to Boston Children's Hospital/Harvard Medical School. He has risen through the ranks and presently holds the Patricia K. Donahoe Chair in Surgery (Pathology). His research efforts have been rewarded by two nine-year MERIT Awards from the National Cancer Institute.

Publications

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  1. Wedel J, Nakayama H, Kochupurakkal NM, Koch J, Klagsbrun M, Bielenberg DR, Briscoe DM. The intragraft microenvironment as a central determinant of chronic rejection or local immunoregulation/tolerance. Curr Opin Organ Transplant. 2017 Feb; 22(1):55-63.
  2. Mucka P, Levonyak N, Geretti E, Zwaans BMM, Li X, Adini I, Klagsbrun M, Adam RM, Bielenberg DR. Inflammation and Lymphedema Are Exacerbated and Prolonged by Neuropilin 2 Deficiency. Am J Pathol. 2016 Nov; 186(11):2803-2812.
  3. Boneschansker L, Nakayama H, Eisenga M, Wedel J, Klagsbrun M, Irimia D, Briscoe DM. Netrin-1 Augments Chemokinesis in CD4+ T Cells In Vitro and Elicits a Proinflammatory Response In Vivo. J Immunol. 2016 Aug 15; 197(4):1389-98.
  4. Shim JW, Sandlund J, Hameed MQ, Blazer-Yost B, Zhou FC, Klagsbrun M, Madsen JR. Excess HB-EGF, which promotes VEGF signaling, leads to hydrocephalus. Sci Rep. 2016 May 31; 6:26794.
  5. Yoshida A, Shimizu A, Asano H, Kadonosono T, Kondoh SK, Geretti E, Mammoto A, Klagsbrun M, Seo MK. VEGF-A/NRP1 stimulates GIPC1 and Syx complex formation to promote RhoA activation and proliferation in skin cancer cells. Biol Open. 2015 Jul 24; 4(9):1063-76.
  6. Nakayama H, Bruneau S, Kochupurakkal N, Coma S, Briscoe DM, Klagsbrun M. Regulation of mTOR Signaling by Semaphorin 3F-Neuropilin 2 Interactions In Vitro and In Vivo. Sci Rep. 2015 Jul 09; 5:11789.
  7. Hofmann NA, Yang J, Trauger SA, Nakayama H, Huang L, Strunk D, Moses MA, Klagsbrun M, Bischoff J, Graier WF. The GPR 55 agonist, L-a-lysophosphatidylinositol, mediates ovarian carcinoma cell-induced angiogenesis. Br J Pharmacol. 2015 Aug; 172(16):4107-18.
  8. Nakayama H, Huang L, Kelly RP, Oudenaarden CR, Dagher A, Hofmann NA, Moses MA, Bischoff J, Klagsbrun M. Infantile hemangioma-derived stem cells and endothelial cells are inhibited by class 3 semaphorins. Biochem Biophys Res Commun. 2015 Aug 14; 464(1):126-32.
  9. Huang L, Nakayama H, Klagsbrun M, Mulliken JB, Bischoff J. Glucose transporter 1-positive endothelial cells in infantile hemangioma exhibit features of facultative stem cells. Stem Cells. 2015 Jan; 33(1):133-45.
  10. Boscolo E, Coma S, Luks VL, Greene AK, Klagsbrun M, Warman ML, Bischoff J. AKT hyper-phosphorylation associated with PI3K mutations in lymphatic endothelial cells from a patient with lymphatic malformation. Angiogenesis. 2015 Apr; 18(2):151-62.
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  12. Panigrahy D, Adini I, Mamluk R, Levonyak N, Bruns CJ, D'Amore PA, Klagsbrun M, Bielenberg DR. Regulation of soluble neuropilin 1, an endogenous angiogenesis inhibitor, in liver development and regeneration. Pathology. 2014 Aug; 46(5):416-23.
  13. Akino T, Han X, Nakayama H, McNeish B, Zurakowski D, Mammoto A, Klagsbrun M, Smith E. Netrin-1 promotes medulloblastoma cell invasiveness and angiogenesis, and demonstrates elevated expression in tumor tissue and urine of patients with pediatric medulloblastoma. Cancer Res. 2014 Jul 15; 74(14):3716-26.
  14. Procaccia V, Nakayama H, Shimizu A, Klagsbrun M. Gleevec/imatinib, an ABL2 kinase inhibitor, protects tumor and endothelial cells from semaphorin-induced cytoskeleton collapse and loss of cell motility. Biochem Biophys Res Commun. 2014 May 30; 448(2):134-8.
  15. Coma S, Allard-Ratick M, Akino T, van Meeteren LA, Mammoto A, Klagsbrun M. GATA2 and Lmo2 control angiogenesis and lymphangiogenesis via direct transcriptional regulation of neuropilin-2. Angiogenesis. 2013 Oct; 16(4):939-52.
  16. Buehler A, Sitaras N, Favret S, Bucher F, Berger S, Pielen A, Joyal JS, Juan AM, Martin G, Schlunck G, Agostini HT, Klagsbrun M, Smith LE, Sapieha P, Stahl A. Semaphorin 3F forms an anti-angiogenic barrier in outer retina. FEBS Lett. 2013 Jun 05; 587(11):1650-5.
  17. Shim JW, Sandlund J, Han CH, Hameed MQ, Connors S, Klagsbrun M, Madsen JR, Irwin N. VEGF, which is elevated in the CSF of patients with hydrocephalus, causes ventriculomegaly and ependymal changes in rats. Exp Neurol. 2013 Sep; 247:703-9.
  18. Snuderl M, Batista A, Kirkpatrick ND, Ruiz de Almodovar C, Riedemann L, Walsh EC, Anolik R, Huang Y, Martin JD, Kamoun W, Knevels E, Schmidt T, Farrar CT, Vakoc BJ, Mohan N, Chung E, Roberge S, Peterson T, Bais C, Zhelyazkova BH, Yip S, Hasselblatt M, Rossig C, Niemeyer E, Ferrara N, Klagsbrun M, Duda DG, Fukumura D, Xu L, Carmeliet P, Jain RK. Targeting placental growth factor/neuropilin 1 pathway inhibits growth and spread of medulloblastoma. Cell. 2013 Feb 28; 152(5):1065-76.
  19. Gerald D, Adini I, Shechter S, Perruzzi C, Varnau J, Hopkins B, Kazerounian S, Kurschat P, Blachon S, Khedkar S, Bagchi M, Sherris D, Prendergast GC, Klagsbrun M, Stuhlmann H, Rigby AC, Nagy JA, Benjamin LE. RhoB controls coordination of adult angiogenesis and lymphangiogenesis following injury by regulating VEZF1-mediated transcription. Nat Commun. 2013; 4:2824.
  20. Shimizu A, Nakayama H, Wang P, König C, Akino T, Sandlund J, Coma S, Italiano JE, Mammoto A, Bielenberg DR, Klagsbrun M. Netrin-1 promotes glioblastoma cell invasiveness and angiogenesis by multiple pathways including activation of RhoA, cathepsin B, and cAMP-response element-binding protein. J Biol Chem. 2013 Jan 25; 288(4):2210-22.
  21. Di Vizio D, Morello M, Dudley AC, Schow PW, Adam RM, Morley S, Mulholland D, Rotinen M, Hager MH, Insabato L, Moses MA, Demichelis F, Lisanti MP, Wu H, Klagsbrun M, Bhowmick NA, Rubin MA, D'Souza-Schorey C, Freeman MR. Large oncosomes in human prostate cancer tissues and in the circulation of mice with metastatic disease. Am J Pathol. 2012 Nov; 181(5):1573-84.
  22. Bielenberg DR, Seth A, Shimizu A, Pelton K, Cristofaro V, Ramachandran A, Zwaans BM, Chen C, Krishnan R, Seth M, Huang L, Takashima S, Klagsbrun M, Sullivan MP, Adam RM. Increased smooth muscle contractility in mice deficient for neuropilin 2. Am J Pathol. 2012 Aug; 181(2):548-59.
  23. Wagner M, Bjerkvig R, Wiig H, Melero-Martin JM, Lin RZ, Klagsbrun M, Dudley AC. Inflamed tumor-associated adipose tissue is a depot for macrophages that stimulate tumor growth and angiogenesis. Angiogenesis. 2012 Sep; 15(3):481-95.
  24. Wong HK, Shimizu A, Kirkpatrick ND, Garkavtsev I, Chan AW, di Tomaso E, Klagsbrun M, Jain RK. Merlin/NF2 regulates angiogenesis in schwannomas through a Rac1/semaphorin 3F-dependent mechanism. Neoplasia. 2012 Feb; 14(2):84-94.
  25. Cao Y, Arbiser J, D'Amato RJ, D'Amore PA, Ingber DE, Kerbel R, Klagsbrun M, Lim S, Moses MA, Zetter B, Dvorak H, Langer R. Forty-year journey of angiogenesis translational research. Sci Transl Med. 2011 Dec 21; 3(114):114rv3.
  26. Grandclement C, Pallandre JR, Valmary Degano S, Viel E, Bouard A, Balland J, Rémy-Martin JP, Simon B, Rouleau A, Boireau W, Klagsbrun M, Ferrand C, Borg C. Neuropilin-2 expression promotes TGF-ß1-mediated epithelial to mesenchymal transition in colorectal cancer cells. PLoS One. 2011; 6(7):e20444.
  27. Coma S, Shimizu A, Klagsbrun M. Hypoxia induces tumor and endothelial cell migration in a semaphorin 3F- and VEGF-dependent manner via transcriptional repression of their common receptor neuropilin 2. Cell Adh Migr. 2011 May-Jun; 5(3):266-75.
  28. Joyal JS, Sitaras N, Binet F, Rivera JC, Stahl A, Zaniolo K, Shao Z, Polosa A, Zhu T, Hamel D, Djavari M, Kunik D, Honoré JC, Picard E, Zabeida A, Varma DR, Hickson G, Mancini J, Klagsbrun M, Costantino S, Beauséjour C, Lachapelle P, Smith LE, Chemtob S, Sapieha P. Ischemic neurons prevent vascular regeneration of neural tissue by secreting semaphorin 3A. Blood. 2011 Jun 02; 117(22):6024-35.
  29. Melero-Martin JM, De Obaldia ME, Allen P, Dudley AC, Klagsbrun M, Bischoff J. Host myeloid cells are necessary for creating bioengineered human vascular networks in vivo. Tissue Eng Part A. 2010 Aug; 16(8):2457-66.
  30. Klagsbrun M, Shimizu A. Semaphorin 3E, an exception to the rule. J Clin Invest. 2010 Aug; 120(8):2658-60.
  31. Geretti E, van Meeteren LA, Shimizu A, Dudley AC, Claesson-Welsh L, Klagsbrun M. A mutated soluble neuropilin-2 B domain antagonizes vascular endothelial growth factor bioactivity and inhibits tumor progression. Mol Cancer Res. 2010 Aug; 8(8):1063-73.
  32. Dudley AC, Udagawa T, Melero-Martin JM, Shih SC, Curatolo A, Moses MA, Klagsbrun M. Bone marrow is a reservoir for proangiogenic myelomonocytic cells but not endothelial cells in spontaneous tumors. Blood. 2010 Oct 28; 116(17):3367-71.
  33. Coma S, Amin DN, Shimizu A, Lasorella A, Iavarone A, Klagsbrun M. Id2 promotes tumor cell migration and invasion through transcriptional repression of semaphorin 3F. Cancer Res. 2010 May 01; 70(9):3823-32.
  34. Matsuda K, Ohga N, Hida Y, Muraki C, Tsuchiya K, Kurosu T, Akino T, Shih SC, Totsuka Y, Klagsbrun M, Shindoh M, Hida K. Isolated tumor endothelial cells maintain specific character during long-term culture. Biochem Biophys Res Commun. 2010 Apr 16; 394(4):947-54.
  35. Akino T, Hida K, Hida Y, Tsuchiya K, Freedman D, Muraki C, Ohga N, Matsuda K, Akiyama K, Harabayashi T, Shinohara N, Nonomura K, Klagsbrun M, Shindoh M. Cytogenetic abnormalities of tumor-associated endothelial cells in human malignant tumors. Am J Pathol. 2009 Dec; 175(6):2657-67.
  36. Aloui Z, Hoos S, Geretti E, Kharmachi H, Haumont PY, Mejdoub H, Klagsbrun M, England P, Gasmi A. Novel svVEGF isoforms from Macrovipera lebetina venom interact with neuropilins. Biochem Biophys Res Commun. 2009 Nov 06; 389(1):10-5.
  37. Dudley AC, Klagsbrun M. Tumor endothelial cells join the resistance. Clin Cancer Res. 2009 Aug 01; 15(15):4787-9.
  38. Dudley AC, Klagsbrun M. Tumor endothelial cells have features of adult stem cells. Cell Cycle. 2009 Jan 15; 8(2):236-8.
  39. Bondeva T, Rüster C, Franke S, Hammerschmid E, Klagsbrun M, Cohen CD, Wolf G. Advanced glycation end-products suppress neuropilin-1 expression in podocytes. Kidney Int. 2009 Mar; 75(6):605-16.
  40. Dudley AC, Khan ZA, Shih SC, Kang SY, Zwaans BM, Bischoff J, Klagsbrun M. Calcification of multipotent prostate tumor endothelium. Cancer Cell. 2008 Sep 09; 14(3):201-11.
  41. Ghosh K, Thodeti CK, Dudley AC, Mammoto A, Klagsbrun M, Ingber DE. Tumor-derived endothelial cells exhibit aberrant Rho-mediated mechanosensing and abnormal angiogenesis in vitro. Proc Natl Acad Sci U S A. 2008 Aug 12; 105(32):11305-10.
  42. Kawamura H, Li X, Goishi K, van Meeteren LA, Jakobsson L, Cébe-Suarez S, Shimizu A, Edholm D, Ballmer-Hofer K, Kjellén L, Klagsbrun M, Claesson-Welsh L. Neuropilin-1 in regulation of VEGF-induced activation of p38MAPK and endothelial cell organization. Blood. 2008 Nov 01; 112(9):3638-49.
  43. Shimizu A, Mammoto A, Italiano JE, Pravda E, Dudley AC, Ingber DE, Klagsbrun M. ABL2/ARG tyrosine kinase mediates SEMA3F-induced RhoA inactivation and cytoskeleton collapse in human glioma cells. J Biol Chem. 2008 Oct 03; 283(40):27230-8.
  44. Dudley AC, Shih SC, Cliffe AR, Hida K, Klagsbrun M. Attenuated p53 activation in tumour-associated stromal cells accompanies decreased sensitivity to etoposide and vincristine. Br J Cancer. 2008 Jul 08; 99(1):118-25.
  45. Amin DN, Bielenberg DR, Lifshits E, Heymach JV, Klagsbrun M. Targeting EGFR activity in blood vessels is sufficient to inhibit tumor growth and is accompanied by an increase in VEGFR-2 dependence in tumor endothelial cells. Microvasc Res. 2008 May; 76(1):15-22.
  46. Geretti E, Shimizu A, Klagsbrun M. Neuropilin structure governs VEGF and semaphorin binding and regulates angiogenesis. Angiogenesis. 2008; 11(1):31-9.
  47. Klagsbrun M, Moses MA. Obituary: M. Judah Folkman (1933-2008). Nature. 2008 Feb 14; 451(7180):781.
  48. Bielenberg DR, Shimizu A, Klagsbrun M. Semaphorin-induced cytoskeletal collapse and repulsion of endothelial cells. Methods Enzymol. 2008; 443:299-314.
  49. Bielenberg DR, Klagsbrun M. Targeting endothelial and tumor cells with semaphorins. Cancer Metastasis Rev. 2007 Dec; 26(3-4):421-31.
  50. Bahary N, Goishi K, Stuckenholz C, Weber G, Leblanc J, Schafer CA, Berman SS, Klagsbrun M, Zon LI. Duplicate VegfA genes and orthologues of the KDR receptor tyrosine kinase family mediate vascular development in the zebrafish. Blood. 2007 Nov 15; 110(10):3627-36.
  51. Geretti E, Shimizu A, Kurschat P, Klagsbrun M. Site-directed mutagenesis in the B-neuropilin-2 domain selectively enhances its affinity to VEGF165, but not to semaphorin 3F. J Biol Chem. 2007 Aug 31; 282(35):25698-707.
  52. Geretti E, Klagsbrun M. Neuropilins: novel targets for anti-angiogenesis therapies. Cell Adh Migr. 2007 Apr-Jun; 1(2):56-61.
  53. Goishi K, Shimizu A, Najarro G, Watanabe S, Rogers R, Zon LI, Klagsbrun M. AlphaA-crystallin expression prevents gamma-crystallin insolubility and cataract formation in the zebrafish cloche mutant lens. Development. 2006 Jul; 133(13):2585-93.
  54. Amin DN, Hida K, Bielenberg DR, Klagsbrun M. Tumor endothelial cells express epidermal growth factor receptor (EGFR) but not ErbB3 and are responsive to EGF and to EGFR kinase inhibitors. Cancer Res. 2006 Feb 15; 66(4):2173-80.
  55. Bielenberg DR, Pettaway CA, Takashima S, Klagsbrun M. Neuropilins in neoplasms: expression, regulation, and function. Exp Cell Res. 2006 Mar 10; 312(5):584-93.
  56. Kurschat P, Bielenberg D, Rossignol-Tallandier M, Stahl A, Klagsbrun M. Neuron restrictive silencer factor NRSF/REST is a transcriptional repressor of neuropilin-1 and diminishes the ability of semaphorin 3A to inhibit keratinocyte migration. J Biol Chem. 2006 Feb 03; 281(5):2721-9.
  57. Mamluk R, Klagsbrun M, Detmar M, Bielenberg DR. Soluble neuropilin targeted to the skin inhibits vascular permeability. Angiogenesis. 2005; 8(3):217-27.
  58. Feldner J, Becker T, Goishi K, Schweitzer J, Lee P, Schachner M, Klagsbrun M, Becker CG. Neuropilin-1a is involved in trunk motor axon outgrowth in embryonic zebrafish. Dev Dyn. 2005 Nov; 234(3):535-49.
  59. Stahl A, Wu X, Wenger A, Klagsbrun M, Kurschat P. Endothelial progenitor cell sprouting in spheroid cultures is resistant to inhibition by osteoblasts: a model for bone replacement grafts. FEBS Lett. 2005 Oct 10; 579(24):5338-42.
  60. Klagsbrun M, Eichmann A. A role for axon guidance receptors and ligands in blood vessel development and tumor angiogenesis. Cytokine Growth Factor Rev. 2005 Aug-Oct; 16(4-5):535-48.
  61. Hida K, Klagsbrun M. A new perspective on tumor endothelial cells: unexpected chromosome and centrosome abnormalities. Cancer Res. 2005 Apr 01; 65(7):2507-10.
  62. Nishi E, Klagsbrun M. Heparin-binding epidermal growth factor-like growth factor (HB-EGF) is a mediator of multiple physiological and pathological pathways. Growth Factors. 2004 Dec; 22(4):253-60.
  63. Hida K, Hida Y, Amin DN, Flint AF, Panigrahy D, Morton CC, Klagsbrun M. Tumor-associated endothelial cells with cytogenetic abnormalities. Cancer Res. 2004 Nov 15; 64(22):8249-55.
  64. Bielenberg DR, Hida Y, Shimizu A, Kaipainen A, Kreuter M, Kim CC, Klagsbrun M. Semaphorin 3F, a chemorepulsant for endothelial cells, induces a poorly vascularized, encapsulated, nonmetastatic tumor phenotype. J Clin Invest. 2004 Nov; 114(9):1260-71.
  65. Kutcher ME, Klagsbrun M, Mamluk R. VEGF is required for the maintenance of dorsal root ganglia blood vessels but not neurons during development. FASEB J. 2004 Dec; 18(15):1952-4.
  66. Bovenkamp DE, Goishi K, Bahary N, Davidson AJ, Zhou Y, Becker T, Becker CG, Zon LI, Klagsbrun M. Expression and mapping of duplicate neuropilin-1 and neuropilin-2 genes in developing zebrafish. Gene Expr Patterns. 2004 Jul; 4(4):361-70.
  67. Parikh AA, Fan F, Liu WB, Ahmad SA, Stoeltzing O, Reinmuth N, Bielenberg D, Bucana CD, Klagsbrun M, Ellis LM. Neuropilin-1 in human colon cancer: expression, regulation, and role in induction of angiogenesis. Am J Pathol. 2004 Jun; 164(6):2139-51.
  68. Goishi K, Klagsbrun M. Vascular endothelial growth factor and its receptors in embryonic zebrafish blood vessel development. Curr Top Dev Biol. 2004; 62:127-52.
  69. Park PW, Foster TJ, Nishi E, Duncan SJ, Klagsbrun M, Chen Y. Activation of syndecan-1 ectodomain shedding by Staphylococcus aureus alpha-toxin and beta-toxin. J Biol Chem. 2004 Jan 02; 279(1):251-8.
  70. Goishi K, Lee P, Davidson AJ, Nishi E, Zon LI, Klagsbrun M. Inhibition of zebrafish epidermal growth factor receptor activity results in cardiovascular defects. Mech Dev. 2003 Jul; 120(7):811-22.
  71. Iwamoto R, Yamazaki S, Asakura M, Takashima S, Hasuwa H, Miyado K, Adachi S, Kitakaze M, Hashimoto K, Raab G, Nanba D, Higashiyama S, Hori M, Klagsbrun M, Mekada E. Heparin-binding EGF-like growth factor and ErbB signaling is essential for heart function. Proc Natl Acad Sci U S A. 2003 Mar 18; 100(6):3221-6.
  72. Rossignol M, Pouysségur J, Klagsbrun M. Characterization of the neuropilin-1 promoter; gene expression is mediated by the transcription factor Sp1. J Cell Biochem. 2003 Mar 01; 88(4):744-57.
  73. Bates D, Taylor GI, Minichiello J, Farlie P, Cichowitz A, Watson N, Klagsbrun M, Mamluk R, Newgreen DF. Neurovascular congruence results from a shared patterning mechanism that utilizes Semaphorin3A and Neuropilin-1. Dev Biol. 2003 Mar 01; 255(1):77-98.
  74. Hospital V, Nishi E, Klagsbrun M, Cohen P, Seidah NG, Prat A. The metalloendopeptidase nardilysin (NRDc) is potently inhibited by heparin-binding epidermal growth factor-like growth factor (HB-EGF). Biochem J. 2002 Oct 01; 367(Pt 1):229-38.
  75. Lee P, Goishi K, Davidson AJ, Mannix R, Zon L, Klagsbrun M. Neuropilin-1 is required for vascular development and is a mediator of VEGF-dependent angiogenesis in zebrafish. Proc Natl Acad Sci U S A. 2002 Aug 06; 99(16):10470-5.
  76. Jin K, Mao XO, Sun Y, Xie L, Jin L, Nishi E, Klagsbrun M, Greenberg DA. Heparin-binding epidermal growth factor-like growth factor: hypoxia-inducible expression in vitro and stimulation of neurogenesis in vitro and in vivo. J Neurosci. 2002 Jul 01; 22(13):5365-73.
  77. Mamluk R, Gechtman Z, Kutcher ME, Gasiunas N, Gallagher J, Klagsbrun M. Neuropilin-1 binds vascular endothelial growth factor 165, placenta growth factor-2, and heparin via its b1b2 domain. J Biol Chem. 2002 Jul 05; 277(27):24818-25.
  78. Takashima S, Kitakaze M, Asakura M, Asanuma H, Sanada S, Tashiro F, Niwa H, Miyazaki Ji J, Hirota S, Kitamura Y, Kitsukawa T, Fujisawa H, Klagsbrun M, Hori M. Targeting of both mouse neuropilin-1 and neuropilin-2 genes severely impairs developmental yolk sac and embryonic angiogenesis. Proc Natl Acad Sci U S A. 2002 Mar 19; 99(6):3657-62.
  79. Kreuter M, Bielenberg D, Hida Y, Hida K, Klagsbrun M. Role of neuropilins and semaphorins in angiogenesis and cancer. Ann Hematol. 2002; 81 Suppl 2:S74.
  80. Soker S, Miao HQ, Nomi M, Takashima S, Klagsbrun M. VEGF165 mediates formation of complexes containing VEGFR-2 and neuropilin-1 that enhance VEGF165-receptor binding. J Cell Biochem. 2002; 85(2):357-68.
  81. Klagsbrun M, Takashima S, Mamluk R. The role of neuropilin in vascular and tumor biology. Adv Exp Med Biol. 2002; 515:33-48.
  82. Soker S, Kaefer M, Johnson M, Klagsbrun M, Atala A, Freeman MR. Vascular endothelial growth factor-mediated autocrine stimulation of prostate tumor cells coincides with progression to a malignant phenotype. Am J Pathol. 2001 Aug; 159(2):651-9.
  83. Nishi E, Prat A, Hospital V, Elenius K, Klagsbrun M. N-arginine dibasic convertase is a specific receptor for heparin-binding EGF-like growth factor that mediates cell migration. EMBO J. 2001 Jul 02; 20(13):3342-50.
  84. Harper J, Gerstenfeld LC, Klagsbrun M. Neuropilin-1 expression in osteogenic cells: down-regulation during differentiation of osteoblasts into osteocytes. J Cell Biochem. 2001; 81(1):82-92.
  85. Miao HQ, Lee P, Lin H, Soker S, Klagsbrun M. Neuropilin-1 expression by tumor cells promotes tumor angiogenesis and progression. FASEB J. 2000 Dec; 14(15):2532-9.
  86. Rossignol M, Gagnon ML, Klagsbrun M. Genomic organization of human neuropilin-1 and neuropilin-2 genes: identification and distribution of splice variants and soluble isoforms. Genomics. 2000 Dec 01; 70(2):211-22.
  87. Kainulainen V, Sundvall M, Määttä JA, Santiestevan E, Klagsbrun M, Elenius K. A natural ErbB4 isoform that does not activate phosphoinositide 3-kinase mediates proliferation but not survival or chemotaxis. J Biol Chem. 2000 Mar 24; 275(12):8641-9.
  88. Gagnon ML, Bielenberg DR, Gechtman Z, Miao HQ, Takashima S, Soker S, Klagsbrun M. Identification of a natural soluble neuropilin-1 that binds vascular endothelial growth factor: In vivo expression and antitumor activity. Proc Natl Acad Sci U S A. 2000 Mar 14; 97(6):2573-8.
  89. Halder JB, Zhao X, Soker S, Paria BC, Klagsbrun M, Das SK, Dey SK. Differential expression of VEGF isoforms and VEGF(164)-specific receptor neuropilin-1 in the mouse uterus suggests a role for VEGF(164) in vascular permeability and angiogenesis during implantation. Genesis. 2000 Mar; 26(3):213-24.
  90. Miao HQ, Klagsbrun M. Neuropilin is a mediator of angiogenesis. Cancer Metastasis Rev. 2000; 19(1-2):29-37.
  91. Gechtman Z, Alonso JL, Raab G, Ingber DE, Klagsbrun M. The shedding of membrane-anchored heparin-binding epidermal-like growth factor is regulated by the Raf/mitogen-activated protein kinase cascade and by cell adhesion and spreading. J Biol Chem. 1999 Oct 01; 274(40):28828-35.
  92. Arbiser JL, Raab G, Rohan RM, Paul S, Hirschi K, Flynn E, Price ER, Fisher DE, Cohen C, Klagsbrun M. Isolation of mouse stromal cells associated with a human tumor using differential diphtheria toxin sensitivity. Am J Pathol. 1999 Sep; 155(3):723-9.
  93. Park JM, Adam RM, Peters CA, Guthrie PD, Sun Z, Klagsbrun M, Freeman MR. AP-1 mediates stretch-induced expression of HB-EGF in bladder smooth muscle cells. Am J Physiol. 1999 Aug; 277(2 Pt 1):C294-301.
  94. Klagsbrun M, Moses MA. Molecular angiogenesis. Chem Biol. 1999 Aug; 6(8):R217-24.
  95. Makinen T, Olofsson B, Karpanen T, Hellman U, Soker S, Klagsbrun M, Eriksson U, Alitalo K. Differential binding of vascular endothelial growth factor B splice and proteolytic isoforms to neuropilin-1. J Biol Chem. 1999 Jul 23; 274(30):21217-22.
  96. Miao HQ, Soker S, Feiner L, Alonso JL, Raper JA, Klagsbrun M. Neuropilin-1 mediates collapsin-1/semaphorin III inhibition of endothelial cell motility: functional competition of collapsin-1 and vascular endothelial growth factor-165. J Cell Biol. 1999 Jul 12; 146(1):233-42.
  97. Harper J, Klagsbrun M. Cartilage to bone--angiogenesis leads the way. Nat Med. 1999 Jun; 5(6):617-8.
  98. Rossignol M, Beggs AH, Pierce EA, Klagsbrun M. Human neuropilin-1 and neuropilin-2 map to 10p12 and 2q34, respectively. Genomics. 1999 May 01; 57(3):459-60.
  99. Paria BC, Elenius K, Klagsbrun M, Dey SK. Heparin-binding EGF-like growth factor interacts with mouse blastocysts independently of ErbB1: a possible role for heparan sulfate proteoglycans and ErbB4 in blastocyst implantation. Development. 1999 May; 126(9):1997-2005.
  100. Elenius K, Choi CJ, Paul S, Santiestevan E, Nishi E, Klagsbrun M. Characterization of a naturally occurring ErbB4 isoform that does not bind or activate phosphatidyl inositol 3-kinase. Oncogene. 1999 Apr 22; 18(16):2607-15.
  101. Gagnon ML, Moy GK, Klagsbrun M. Characterization of the promoter for the human antisense fibroblast growth factor-2 gene; regulation by Ets in Jurkat T cells. J Cell Biochem. 1999 Mar 15; 72(4):492-506.
  102. Nakano N, Higashiyama S, Takashima S, Tsuruoka N, Klagsbrun M, Taniguchi N. Purification and characterization of a novel vascular endothelial cell growth inhibitor secreted by macrophage-like U-937 cells. J Biochem. 1999 Feb; 125(2):368-74.
  103. Klagsbrun M. Angiogenesis and cancer: AACR special conference in cancer research. American Association for Cancer Research. Cancer Res. 1999 Jan 15; 59(2):487-90.
  104. Giraudo E, Primo L, Audero E, Gerber HP, Koolwijk P, Soker S, Klagsbrun M, Ferrara N, Bussolino F. Tumor necrosis factor-alpha regulates expression of vascular endothelial growth factor receptor-2 and of its co-receptor neuropilin-1 in human vascular endothelial cells. J Biol Chem. 1998 Aug 21; 273(34):22128-35.
  105. Yancopoulos GD, Klagsbrun M, Folkman J. Vasculogenesis, angiogenesis, and growth factors: ephrins enter the fray at the border. Cell. 1998 May 29; 93(5):661-4.
  106. Dethlefsen SM, Raab G, Moses MA, Adam RM, Klagsbrun M, Freeman MR. Extracellular calcium influx stimulates metalloproteinase cleavage and secretion of heparin-binding EGF-like growth factor independently of protein kinase C. J Cell Biochem. 1998 May 01; 69(2):143-53.
  107. Soker S, Takashima S, Miao HQ, Neufeld G, Klagsbrun M. Neuropilin-1 is expressed by endothelial and tumor cells as an isoform-specific receptor for vascular endothelial growth factor. Cell. 1998 Mar 20; 92(6):735-45.
  108. Freeman MR, Paul S, Kaefer M, Ishikawa M, Adam RM, Renshaw AA, Elenius K, Klagsbrun M. Heparin-binding EGF-like growth factor in the human prostate: synthesis predominantly by interstitial and vascular smooth muscle cells and action as a carcinoma cell mitogen. J Cell Biochem. 1998 Mar 01; 68(3):328-38.
  109. Soker S, Gollamudi-Payne S, Fidder H, Charmahelli H, Klagsbrun M. Inhibition of vascular endothelial growth factor (VEGF)-induced endothelial cell proliferation by a peptide corresponding to the exon 7-encoded domain of VEGF165. J Biol Chem. 1997 Dec 12; 272(50):31582-8.
  110. Suzuki M, Raab G, Moses MA, Fernandez CA, Klagsbrun M. Matrix metalloproteinase-3 releases active heparin-binding EGF-like growth factor by cleavage at a specific juxtamembrane site. J Biol Chem. 1997 Dec 12; 272(50):31730-7.
  111. Raab G, Klagsbrun M. Heparin-binding EGF-like growth factor. Biochim Biophys Acta. 1997 Dec 09; 1333(3):F179-99.
  112. Elenius K, Corfas G, Paul S, Choi CJ, Rio C, Plowman GD, Klagsbrun M. A novel juxtamembrane domain isoform of HER4/ErbB4. Isoform-specific tissue distribution and differential processing in response to phorbol ester. J Biol Chem. 1997 Oct 17; 272(42):26761-8.
  113. Gallo RL, Dorschner RA, Takashima S, Klagsbrun M, Eriksson E, Bernfield M. Endothelial cell surface alkaline phosphatase activity is induced by IL-6 released during wound repair. J Invest Dermatol. 1997 Oct; 109(4):597-603.
  114. Yayon A, Ma YS, Safran M, Klagsbrun M, Halaban R. Suppression of autocrine cell proliferation and tumorigenesis of human melanoma cells and fibroblast growth factor transformed fibroblasts by a kinase-deficient FGF receptor 1: evidence for the involvement of Src-family kinases. Oncogene. 1997 Jun 26; 14(25):2999-3009.
  115. McCarthy SA, Chen D, Yang BS, Garcia Ramirez JJ, Cherwinski H, Chen XR, Klagsbrun M, Hauser CA, Ostrowski MC, McMahon M. Rapid phosphorylation of Ets-2 accompanies mitogen-activated protein kinase activation and the induction of heparin-binding epidermal growth factor gene expression by oncogenic Raf-1. Mol Cell Biol. 1997 May; 17(5):2401-12.
  116. Elenius K, Paul S, Allison G, Sun J, Klagsbrun M. Activation of HER4 by heparin-binding EGF-like growth factor stimulates chemotaxis but not proliferation. EMBO J. 1997 Mar 17; 16(6):1268-78.
  117. Asano K, Nakamura H, Lilly CM, Klagsbrun M, Drazen JM. Interferon gamma induces prostaglandin G/H synthase-2 through an autocrine loop via the epidermal growth factor receptor in human bronchial epithelial cells. J Clin Invest. 1997 Mar 01; 99(5):1057-63.
  118. Freeman MR, Yoo JJ, Raab G, Soker S, Adam RM, Schneck FX, Renshaw AA, Klagsbrun M, Atala A. Heparin-binding EGF-like growth factor is an autocrine growth factor for human urothelial cells and is synthesized by epithelial and smooth muscle cells in the human bladder. J Clin Invest. 1997 Mar 01; 99(5):1028-36.
  119. Takashima S, Klagsbrun M. Inhibition of endothelial cell growth by macrophage-like U-937 cell-derived oncostatin M, leukemia inhibitory factor, and transforming growth factor beta1. J Biol Chem. 1996 Oct 04; 271(40):24901-6.
  120. Klagsbrun M, D'Amore PA. Vascular endothelial growth factor and its receptors. Cytokine Growth Factor Rev. 1996 Oct; 7(3):259-70.
  121. Riese DJ, Kim ED, Elenius K, Buckley S, Klagsbrun M, Plowman GD, Stern DF. The epidermal growth factor receptor couples transforming growth factor-alpha, heparin-binding epidermal growth factor-like factor, and amphiregulin to Neu, ErbB-3, and ErbB-4. J Biol Chem. 1996 Aug 16; 271(33):20047-52.
  122. Marikovsky M, Vogt P, Eriksson E, Rubin JS, Taylor WG, Joachim S, Klagsbrun M. Wound fluid-derived heparin-binding EGF-like growth factor (HB-EGF) is synergistic with insulin-like growth factor-I for Balb/MK keratinocyte proliferation. J Invest Dermatol. 1996 Apr; 106(4):616-21.
  123. Gitay-Goren H, Cohen T, Tessler S, Soker S, Gengrinovitch S, Rockwell P, Klagsbrun M, Levi BZ, Neufeld G. Selective binding of VEGF121 to one of the three vascular endothelial growth factor receptors of vascular endothelial cells. J Biol Chem. 1996 Mar 08; 271(10):5519-23.
  124. Soker S, Fidder H, Neufeld G, Klagsbrun M. Characterization of novel vascular endothelial growth factor (VEGF) receptors on tumor cells that bind VEGF165 via its exon 7-encoded domain. J Biol Chem. 1996 Mar 08; 271(10):5761-7.
  125. Moses MA, Marikovsky M, Harper JW, Vogt P, Eriksson E, Klagsbrun M, Langer R. Temporal study of the activity of matrix metalloproteinases and their endogenous inhibitors during wound healing. J Cell Biochem. 1996 Mar 01; 60(3):379-86.
  126. Raab G, Kover K, Paria BC, Dey SK, Ezzell RM, Klagsbrun M. Mouse preimplantation blastocysts adhere to cells expressing the transmembrane form of heparin-binding EGF-like growth factor. Development. 1996 Feb; 122(2):637-45.
  127. Shishido Y, Sharma KD, Higashiyama S, Klagsbrun M, Mekada E. Heparin-like molecules on the cell surface potentiate binding of diphtheria toxin to the diphtheria toxin receptor/membrane-anchored heparin-binding epidermal growth factor-like growth factor. J Biol Chem. 1995 Dec 08; 270(49):29578-85.
  128. Freeman MR, Schneck FX, Gagnon ML, Corless C, Soker S, Niknejad K, Peoples GE, Klagsbrun M. Peripheral blood T lymphocytes and lymphocytes infiltrating human cancers express vascular endothelial growth factor: a potential role for T cells in angiogenesis. Cancer Res. 1995 Sep 15; 55(18):4140-5.
  129. Mangrulkar RS, Ono M, Ishikawa M, Takashima S, Klagsbrun M, Nowak RA. Isolation and characterization of heparin-binding growth factors in human leiomyomas and normal myometrium. Biol Reprod. 1995 Sep; 53(3):636-46.
  130. Chen X, Raab G, Deutsch U, Zhang J, Ezzell RM, Klagsbrun M. Induction of heparin-binding EGF-like growth factor expression during myogenesis. Activation of the gene by MyoD and localization of the transmembrane form of the protein on the myotube surface. J Biol Chem. 1995 Aug 04; 270(31):18285-94.
  131. Goishi K, Higashiyama S, Klagsbrun M, Nakano N, Umata T, Ishikawa M, Mekada E, Taniguchi N. Phorbol ester induces the rapid processing of cell surface heparin-binding EGF-like growth factor: conversion from juxtacrine to paracrine growth factor activity. Mol Biol Cell. 1995 Aug; 6(8):967-80.
  132. Peoples GE, Blotnick S, Takahashi K, Freeman MR, Klagsbrun M, Eberlein TJ. T lymphocytes that infiltrate tumors and atherosclerotic plaques produce heparin-binding epidermal growth factor-like growth factor and basic fibroblast growth factor: a potential pathologic role. Proc Natl Acad Sci U S A. 1995 Jul 03; 92(14):6547-51.
  133. Pathak BG, Gilbert DJ, Harrison CA, Luetteke NC, Chen X, Klagsbrun M, Plowman GD, Copeland NG, Jenkins NA, Lee DC. Mouse chromosomal location of three EGF receptor ligands: amphiregulin (Areg), betacellulin (Btc), and heparin-binding EGF (Hegfl). Genomics. 1995 Jul 01; 28(1):116-8.
  134. Cook PW, Damm D, Garrick BL, Wood KM, Karkaria CE, Higashiyama S, Klagsbrun M, Abraham JA. Carboxyl-terminal truncation of leucine76 converts heparin-binding EGF-like growth factor from a heparin-enhancible to a heparin-suppressible growth factor. J Cell Physiol. 1995 May; 163(2):407-17.
  135. Gately S, Tsanaclis AM, Takano S, Klagsbrun M, Brem S. Cells transfected with the basic fibroblast growth factor gene fused to a signal sequence are invasive in vitro and in situ in the brain. Neurosurgery. 1995 Apr; 36(4):780-8.
  136. Higashiyama S, Iwamoto R, Goishi K, Raab G, Taniguchi N, Klagsbrun M, Mekada E. The membrane protein CD9/DRAP 27 potentiates the juxtacrine growth factor activity of the membrane-anchored heparin-binding EGF-like growth factor. J Cell Biol. 1995 Mar; 128(5):929-38.
  137. Mitamura T, Higashiyama S, Taniguchi N, Klagsbrun M, Mekada E. Diphtheria toxin binds to the epidermal growth factor (EGF)-like domain of human heparin-binding EGF-like growth factor/diphtheria toxin receptor and inhibits specifically its mitogenic activity. J Biol Chem. 1995 Jan 20; 270(3):1015-9.
  138. Moses MA, Klagsbrun M, Shing Y. The role of growth factors in vascular cell development and differentiation. Int Rev Cytol. 1995; 161:1-48.
  139. no M, Raab G, Lau K, Abraham JA, Klagsbrun M. Purification and characterization of transmembrane forms of heparin-binding EGF-like growth factor. J Biol Chem. 1994 Dec 09; 269(49):31315-21.
  140. Gallo RL, Ono M, Povsic T, Page C, Eriksson E, Klagsbrun M, Bernfield M. Syndecans, cell surface heparan sulfate proteoglycans, are induced by a proline-rich antimicrobial peptide from wounds. Proc Natl Acad Sci U S A. 1994 Nov 08; 91(23):11035-9.
  141. Raab G, Higashiyama S, Hetelekidis S, Abraham JA, Damm D, Ono M, Klagsbrun M. Biosynthesis and processing by phorbol ester of the cells surface-associated precursor form of heparin-binding EGF-like growth factor. Biochem Biophys Res Commun. 1994 Oct 28; 204(2):592-7.
  142. Wang XN, Das SK, Damm D, Klagsbrun M, Abraham JA, Dey SK. Differential regulation of heparin-binding epidermal growth factor-like growth factor in the adult ovariectomized mouse uterus by progesterone and estrogen. Endocrinology. 1994 Sep; 135(3):1264-71.
  143. Mesri EA, Ono M, Kreitman RJ, Klagsbrun M, Pastan I. The heparin-binding domain of heparin-binding EGF-like growth factor can target Pseudomonas exotoxin to kill cells exclusively through heparan sulfate proteoglycans. J Cell Sci. 1994 Sep; 107 ( Pt 9):2599-608.
  144. Iwamoto R, Higashiyama S, Mitamura T, Taniguchi N, Klagsbrun M, Mekada E. Heparin-binding EGF-like growth factor, which acts as the diphtheria toxin receptor, forms a complex with membrane protein DRAP27/CD9, which up-regulates functional receptors and diphtheria toxin sensitivity. EMBO J. 1994 May 15; 13(10):2322-30.
  145. Das SK, Wang XN, Paria BC, Damm D, Abraham JA, Klagsbrun M, Andrews GK, Dey SK. Heparin-binding EGF-like growth factor gene is induced in the mouse uterus temporally by the blastocyst solely at the site of its apposition: a possible ligand for interaction with blastocyst EGF-receptor in implantation. Development. 1994 May; 120(5):1071-83.
  146. Blotnick S, Peoples GE, Freeman MR, Eberlein TJ, Klagsbrun M. T lymphocytes synthesize and export heparin-binding epidermal growth factor-like growth factor and basic fibroblast growth factor, mitogens for vascular cells and fibroblasts: differential production and release by CD4+ and CD8+ T cells. Proc Natl Acad Sci U S A. 1994 Apr 12; 91(8):2890-94.
  147. Nakano T, Raines EW, Abraham JA, Klagsbrun M, Ross R. Lysophosphatidylcholine upregulates the level of heparin-binding epidermal growth factor-like growth factor mRNA in human monocytes. Proc Natl Acad Sci U S A. 1994 Feb 01; 91(3):1069-73.
  148. Higashiyama S, Abraham JA, Klagsbrun M. Heparin-binding EGF-like growth factor synthesis by smooth muscle cells. Horm Res. 1994; 42(1-2):9-13.
  149. Powell PP, Klagsbrun M. Regulation of basic fibroblast growth factor mRNA expression in rat C6 glioma cells. Exp Cell Res. 1993 Dec; 209(2):224-30.
  150. Klagsbrun M, Dluz S. Smooth muscle cell and endothelial cell growth factors. Trends Cardiovasc Med. 1993 Nov-Dec; 3(6):213-7.
  151. Nakano T, Raines EW, Abraham JA, Wenzel FG, Higashiyama S, Klagsbrun M, Ross R. Glucocorticoid inhibits thrombin-induced expression of platelet-derived growth factor A-chain and heparin-binding epidermal growth factor-like growth factor in human aortic smooth muscle cells. J Biol Chem. 1993 Oct 25; 268(30):22941-7.
  152. Klagsbrun M, Soker S. VEGF/VPF: the angiogenesis factor found? Curr Biol. 1993 Oct 01; 3(10):699-702.
  153. Powell PP, Klagsbrun M, Abraham JA, Jones RC. Eosinophils expressing heparin-binding EGF-like growth factor mRNA localize around lung microvessels in pulmonary hypertension. Am J Pathol. 1993 Sep; 143(3):784-93.
  154. Dluz SM, Higashiyama S, Damm D, Abraham JA, Klagsbrun M. Heparin-binding epidermal growth factor-like growth factor expression in cultured fetal human vascular smooth muscle cells. Induction of mRNA levels and secretion of active mitogen. J Biol Chem. 1993 Aug 25; 268(24):18330-4.
  155. Higashiyama S, Abraham JA, Klagsbrun M. Heparin-binding EGF-like growth factor stimulation of smooth muscle cell migration: dependence on interactions with cell surface heparan sulfate. J Cell Biol. 1993 Aug; 122(4):933-40.
  156. Marikovsky M, Breuing K, Liu PY, Eriksson E, Higashiyama S, Farber P, Abraham J, Klagsbrun M. Appearance of heparin-binding EGF-like growth factor in wound fluid as a response to injury. Proc Natl Acad Sci U S A. 1993 May 01; 90(9):3889-93.
  157. Frim DM, Uhler TA, Short MP, Ezzedine ZD, Klagsbrun M, Breakefield XO, Isacson O. Effects of biologically delivered NGF, BDNF and bFGF on striatal excitotoxic lesions. Neuroreport. 1993 Apr; 4(4):367-70.
  158. Abraham JA, Damm D, Bajardi A, Miller J, Klagsbrun M, Ezekowitz RA. Heparin-binding EGF-like growth factor: characterization of rat and mouse cDNA clones, protein domain conservation across species, and transcript expression in tissues. Biochem Biophys Res Commun. 1993 Jan 15; 190(1):125-33.
  159. Trippel SB, Whelan MC, Klagsbrun M, Doctrow SR. Interaction of basic fibroblast growth factor with bovine growth plate chondrocytes. J Orthop Res. 1992 Sep; 10(5):638-46.
  160. Klagsbrun M. Mediators of angiogenesis: the biological significance of basic fibroblast growth factor (bFGF)-heparin and heparan sulfate interactions. Semin Cancer Biol. 1992 Apr; 3(2):81-7.
  161. Higashiyama S, Lau K, Besner GE, Abraham JA, Klagsbrun M. Structure of heparin-binding EGF-like growth factor. Multiple forms, primary structure, and glycosylation of the mature protein. J Biol Chem. 1992 Mar 25; 267(9):6205-12.
  162. Brem H, Klagsbrun M. The role of fibroblast growth factors and related oncogenes in tumor growth. Cancer Treat Res. 1992; 63:211-31.
  163. Klagsbrun M. Regulators of angiogenesis: stimulators, inhibitors, and extracellular matrix. J Cell Biochem. 1991 Nov; 47(3):199-200.
  164. Klagsbrun M, Baird A. A dual receptor system is required for basic fibroblast growth factor activity. Cell. 1991 Oct 18; 67(2):229-31.
  165. Weich HA, Iberg N, Klagsbrun M, Folkman J. Transcriptional regulation of basic fibroblast growth factor gene expression in capillary endothelial cells. J Cell Biochem. 1991 Oct; 47(2):158-64.
  166. Kandel J, Bossy-Wetzel E, Radvanyi F, Klagsbrun M, Folkman J, Hanahan D. Neovascularization is associated with a switch to the export of bFGF in the multistep development of fibrosarcoma. Cell. 1991 Sep 20; 66(6):1095-104.
  167. Edelman ER, Mathiowitz E, Langer R, Klagsbrun M. Controlled and modulated release of basic fibroblast growth factor. Biomaterials. 1991 Sep; 12(7):619-26.
  168. Besner GE, Klagsbrun M. Macrophages secrete a heparin-binding inhibitor of endothelial cell growth. Microvasc Res. 1991 Sep; 42(2):187-97.
  169. Klagsbrun M. Angiogenic factors: regulators of blood supply-side biology. FGF, endothelial cell growth factors and angiogenesis: a keystone symposium, Keystone, CO, USA, April 1-7, 1991. New Biol. 1991 Aug; 3(8):745-9.
  170. Powell PP, Klagsbrun M. Three forms of rat basic fibroblast growth factor are made from a single mRNA and localize to the nucleus. J Cell Physiol. 1991 Aug; 148(2):202-10.
  171. Powell PP, Finklestein SP, Dionne CA, Jaye M, Klagsbrun M. Temporal, differential and regional expression of mRNA for basic fibroblast growth factor in the developing and adult rat brain. Brain Res Mol Brain Res. 1991 Aug; 11(1):71-7.
  172. Baird A, Klagsbrun M. The fibroblast growth factor family. Cancer Cells. 1991 Jun; 3(6):239-43.
  173. Yayon A, Klagsbrun M, Esko JD, Leder P, Ornitz DM. Cell surface, heparin-like molecules are required for binding of basic fibroblast growth factor to its high affinity receptor. Cell. 1991 Feb 22; 64(4):841-8.
  174. Higashiyama S, Abraham JA, Miller J, Fiddes JC, Klagsbrun M. A heparin-binding growth factor secreted by macrophage-like cells that is related to EGF. Science. 1991 Feb 22; 251(4996):936-9.
  175. Vlodavsky I, Fuks Z, Ishai-Michaeli R, Bashkin P, Levi E, Korner G, Bar-Shavit R, Klagsbrun M. Extracellular matrix-resident basic fibroblast growth factor: implication for the control of angiogenesis. J Cell Biochem. 1991 Feb; 45(2):167-76.
  176. Munaim SI, Klagsbrun M, Toole BP. Hyaluronan-dependent pericellular coats of chick embryo limb mesodermal cells: induction by basic fibroblast growth factor. Dev Biol. 1991 Feb; 143(2):297-302.
  177. Brigstock DR, Sasse J, Klagsbrun M. Subcellular distribution of basic fibroblast growth factor in human hepatoma cells. Growth Factors. 1991; 4(3):189-96.
  178. Brigstock DR, Klagsbrun M. Subcellular distribution of multiple molecular weight forms of bFGF in hepatoma cells. Ann N Y Acad Sci. 1991; 638:427-30.
  179. Vlodavsky I, Bashkin P, Ishai-Michaeli R, Chajek-Shaul T, Bar-Shavit R, Haimovitz-Friedman A, Klagsbrun M, Fuks Z. Sequestration and release of basic fibroblast growth factor. Ann N Y Acad Sci. 1991; 638:207-20.
  180. Klagsbrun M, D'Amore PA. Regulators of angiogenesis. Annu Rev Physiol. 1991; 53:217-39.
  181. Rogelj S, Stern D, Klagsbrun M. Construction and expression of transforming gene resulting from fusion of basic fibroblast growth factor gene with signal peptide sequence. Methods Enzymol. 1991; 198:117-24.
  182. Finklestein SP, Caday CG, Kano M, Berlove DJ, Hsu CY, Moskowitz M, Klagsbrun M. Growth factor expression after stroke. Stroke. 1990 Nov; 21(11 Suppl):III122-4.
  183. Yayon A, Klagsbrun M. Autocrine regulation of cell growth and transformation by basic fibroblast growth factor. Cancer Metastasis Rev. 1990 Nov; 9(3):191-202.
  184. Klagsbrun M. The affinity of fibroblast growth factors (FGFs) for heparin; FGF-heparan sulfate interactions in cells and extracellular matrix. Curr Opin Cell Biol. 1990 Oct; 2(5):857-63.
  185. Besner G, Higashiyama S, Klagsbrun M. Isolation and characterization of a macrophage-derived heparin-binding growth factor. Cell Regul. 1990 Oct; 1(11):811-9.
  186. Yayon A, Klagsbrun M. Autocrine transformation by chimeric signal peptide-basic fibroblast growth factor: reversal by suramin. Proc Natl Acad Sci U S A. 1990 Jul; 87(14):5346-50.
  187. Caday CG, Klagsbrun M, Fanning PJ, Mirzabegian A, Finklestein SP. Fibroblast growth factor (FGF) levels in the developing rat brain. Brain Res Dev Brain Res. 1990 Mar 01; 52(1-2):241-6.
  188. Casscells W, Speir E, Sasse J, Klagsbrun M, Allen P, Lee M, Calvo B, Chiba M, Haggroth L, Folkman J, et al. Isolation, characterization, and localization of heparin-binding growth factors in the heart. J Clin Invest. 1990 Feb; 85(2):433-41.
  189. Weich HA, Iberg N, Klagsbrun M, Folkman J. Expression of acidic and basic fibroblast growth factors in human and bovine vascular smooth muscle cells. Growth Factors. 1990; 2(4):313-20.
  190. Brigstock DR, Klagsbrun M, Sasse J, Farber PA, Iberg N. Species-specific high molecular weight forms of basic fibroblast growth factor. Growth Factors. 1990; 4(1):45-52.
  191. Finklestein SP, Fanning PJ, Caday CG, Powell PP, Foster J, Clifford EM, Klagsbrun M. Increased levels of basic fibroblast growth factor (bFGF) following focal brain injury. Restor Neurol Neurosci. 1990 Jan 01; 1(6):387-94.
  192. Iberg N, Rogelj S, Fanning P, Klagsbrun M. Purification of 18- and 22-kDa forms of basic fibroblast growth factor from rat cells transformed by the ras oncogene. J Biol Chem. 1989 Nov 25; 264(33):19951-5.
  193. Rogelj S, Klagsbrun M, Atzmon R, Kurokawa M, Haimovitz A, Fuks Z, Vlodavsky I. Basic fibroblast growth factor is an extracellular matrix component required for supporting the proliferation of vascular endothelial cells and the differentiation of PC12 cells. J Cell Biol. 1989 Aug; 109(2):823-31.
  194. Kurokawa M, Doctrow SR, Klagsbrun M. Neutralizing antibodies inhibit the binding of basic fibroblast growth factor to its receptor but not to heparin. J Biol Chem. 1989 May 05; 264(13):7686-91.
  195. Klagsbrun M, Edelman ER. Biological and biochemical properties of fibroblast growth factors. Implications for the pathogenesis of atherosclerosis. Arteriosclerosis. 1989 May-Jun; 9(3):269-78.
  196. Prats H, Kaghad M, Prats AC, Klagsbrun M, Lélias JM, Liauzun P, Chalon P, Tauber JP, Amalric F, Smith JA, et al. High molecular mass forms of basic fibroblast growth factor are initiated by alternative CUG codons. Proc Natl Acad Sci U S A. 1989 Mar; 86(6):1836-40.
  197. Bashkin P, Doctrow S, Klagsbrun M, Svahn CM, Folkman J, Vlodavsky I. Basic fibroblast growth factor binds to subendothelial extracellular matrix and is released by heparitinase and heparin-like molecules. Biochemistry. 1989 Feb 21; 28(4):1737-43.
  198. Klagsbrun M. The fibroblast growth factor family: structural and biological properties. Prog Growth Factor Res. 1989; 1(4):207-35.
  199. Buckley-Sturrock A, Woodward SC, Senior RM, Griffin GL, Klagsbrun M, Davidson JM. Differential stimulation of collagenase and chemotactic activity in fibroblasts derived from rat wound repair tissue and human skin by growth factors. J Cell Physiol. 1989 Jan; 138(1):70-8.
  200. Rogelj S, Weinberg RA, Fanning P, Klagsbrun M. Characterization of tumors produced by signal peptide-basic fibroblast growth factor-transformed cells. J Cell Biochem. 1989 Jan; 39(1):13-23.
  201. Shing Y, Klagsbrun M, Folkman J. A new method for purifying heparin-binding growth factors. Ann N Y Acad Sci. 1989; 556:166-72.
  202. Munaim SI, Klagsbrun M, Toole BP. Developmental changes in fibroblast growth factor in the chicken embryo limb bud. Proc Natl Acad Sci U S A. 1988 Nov; 85(21):8091-3.
  203. Finklestein SP, Apostolides PJ, Caday CG, Prosser J, Philips MF, Klagsbrun M. Increased basic fibroblast growth factor (bFGF) immunoreactivity at the site of focal brain wounds. Brain Res. 1988 Sep 20; 460(2):253-9.
  204. Folkman J, Klagsbrun M, Sasse J, Wadzinski M, Ingber D, Vlodavsky I. A heparin-binding angiogenic protein--basic fibroblast growth factor--is stored within basement membrane. Am J Pathol. 1988 Feb; 130(2):393-400.
  205. Rogelj S, Weinberg RA, Fanning P, Klagsbrun M. Basic fibroblast growth factor fused to a signal peptide transforms cells. Nature. 1988 Jan 14; 331(6152):173-5.
  206. Hannan RL, Kourembanas S, Flanders KC, Rogelj SJ, Roberts AB, Faller DV, Klagsbrun M. Endothelial cells synthesize basic fibroblast growth factor and transforming growth factor beta. Growth Factors. 1988; 1(1):7-17.
  207. Klagsbrun M. Nutrition Classics. Proceedings of the National Academy of Sciences of the United States of America, October 1978, Volume 75, Number 10: Human milk stimulates DNA synthesis and cellular proliferation in cultured fibroblasts. By Michael Klagsbrun. Nutr Rev. 1988 Jan; 46(1):21-3.
  208. Klagsbrun M, Vlodavsky I. Biosynthesis and storage of basic fibroblast growth factor (bFGF) by endothelial cells: implication for the mechanism of action of angiogenesis. Prog Clin Biol Res. 1988; 266:55-61.
  209. Vlodavsky I, Eldor A, Bar-Ner M, Fridman R, Cohen IR, Klagsbrun M. Heparan sulfate degradation in tumor cell invasion and angiogenesis. Adv Exp Med Biol. 1988; 233:201-10.
  210. Hamerman D, Taylor S, Kirschenbaum I, Klagsbrun M, Raines EW, Ross R, Thomas KA. Growth factors with heparin binding affinity in human synovial fluid. Proc Soc Exp Biol Med. 1987 Dec; 186(3):384-9.
  211. Folkman J, Klagsbrun M. Vascular physiology. A family of angiogenic peptides. Nature. 1987 Oct 22-28; 329(6141):671-2.
  212. Vlodavsky I, Fridman R, Sullivan R, Sasse J, Klagsbrun M. Aortic endothelial cells synthesize basic fibroblast growth factor which remains cell associated and platelet-derived growth factor-like protein which is secreted. J Cell Physiol. 1987 Jun; 131(3):402-8.
  213. Shing Y, Klagsbrun M. Purification and characterization of a bovine colostrum-derived growth factor. Mol Endocrinol. 1987 May; 1(5):335-8.
  214. Klagsbrun M, Smith S, Sullivan R, Shing Y, Davidson S, Smith JA, Sasse J. Multiple forms of basic fibroblast growth factor: amino-terminal cleavages by tumor cell- and brain cell-derived acid proteinases. Proc Natl Acad Sci U S A. 1987 Apr; 84(7):1839-43.
  215. Vlodavsky I, Folkman J, Sullivan R, Fridman R, Ishai-Michaeli R, Sasse J, Klagsbrun M. Endothelial cell-derived basic fibroblast growth factor: synthesis and deposition into subendothelial extracellular matrix. Proc Natl Acad Sci U S A. 1987 Apr; 84(8):2292-6.
  216. Nichols WK, Marken JM, Buckley A, Klagsbrun M, Davidson JM. Differential effects of cartilage-derived growth factor stimulation of collagen secretion by bovine aortic and microvascular endothelial cells. Coll Relat Res. 1987 Feb; 6(6):505-14.
  217. Folkman J, Klagsbrun M. Angiogenic factors. Science. 1987 Jan 23; 235(4787):442-7.
  218. Biller JA, Montgomery RK, Grand RJ, Klagsbrun M, Rosenthal A. Characterisation of humoral trophic factors involved in intestinal adaptation using a 3T3 cell growth factor assay. Gut. 1987; 28 Suppl:243-7.
  219. Sasse J, Sullivan R, Klagsbrun M. Purification of cartilage-derived growth factors. Methods Enzymol. 1987; 146:320-5.
  220. Wadzinski MG, Folkman J, Sasse J, Devey K, Ingber D, Klagsbrun M. Heparin-binding angiogenesis factors: detection by immunological methods. Clin Physiol Biochem. 1987; 5(3-4):200-9.
  221. Shing Y, Davidson S, Klagsbrun M. Purification of polypeptide growth factors from milk. Methods Enzymol. 1987; 146:42-8.
  222. Klagsbrun M, Sullivan R, Smith S, Rybka R, Shing YE. Purification of endothelial cell growth factors by heparin affinity chromatography. Methods Enzymol. 1987; 147:95-105.
  223. Chodak GW, Shing Y, Borge M, Judge SM, Klagsbrun M. Presence of heparin binding growth factor in mouse bladder tumors and urine from mice with bladder cancer. Cancer Res. 1986 Nov; 46(11):5507-10.
  224. Hauschka PV, Mavrakos AE, Iafrati MD, Doleman SE, Klagsbrun M. Growth factors in bone matrix. Isolation of multiple types by affinity chromatography on heparin-Sepharose. J Biol Chem. 1986 Sep 25; 261(27):12665-74.
  225. Biller JA, Montgomery RK, Grand RJ, Klagsbrun M, Rosenthal A. Use of a 3T3 cell growth factor assay for the delineation and characterization of humoral trophic factors involved in intestinal adaptation in the rat. Gastroenterology. 1986 Aug; 91(2):448-55.
  226. Hamerman D, Sasse J, Klagsbrun M. A cartilage-derived growth factor enhances hyaluronate synthesis and diminishes sulfated glycosaminoglycan synthesis in chondrocytes. J Cell Physiol. 1986 May; 127(2):317-22.
  227. Klagsbrun M, Sasse J, Sullivan R, Smith JA. Human tumor cells synthesize an endothelial cell growth factor that is structurally related to basic fibroblast growth factor. Proc Natl Acad Sci U S A. 1986 Apr; 83(8):2448-52.
  228. Lobb R, Sasse J, Sullivan R, Shing Y, D'Amore P, Jacobs J, Klagsbrun M. Purification and characterization of heparin-binding endothelial cell growth factors. J Biol Chem. 1986 Feb 05; 261(4):1924-8.
  229. Dai S, Klagsbrun M, Shing YW. Human milk-derived growth factor prevents duodenal ulcer formation. Pediatr Res. 1985 Sep; 19(9):916-8.
  230. Levenson R, Iwata K, Klagsbrun M, Young DA. Growth factor- and dexamethasone-induced proteins in Swiss 3T3 cells. Relationship to DNA synthesis. J Biol Chem. 1985 Jul 05; 260(13):8056-63.
  231. Davidson JM, Klagsbrun M, Hill KE, Buckley A, Sullivan R, Brewer PS, Woodward SC. Accelerated wound repair, cell proliferation, and collagen accumulation are produced by a cartilage-derived growth factor. J Cell Biol. 1985 Apr; 100(4):1219-27.
  232. Hamerman D, Klagsbrun M. Osteoarthritis. Emerging evidence for cell interactions in the breakdown and remodeling of cartilage. Am J Med. 1985 Mar; 78(3):495-9.
  233. Sullivan R, Klagsbrun M. Purification of cartilage-derived growth factor by heparin affinity chromatography. J Biol Chem. 1985 Feb 25; 260(4):2399-403.
  234. Klagsbrun M, Shing Y. Heparin affinity of anionic and cationic capillary endothelial cell growth factors: analysis of hypothalamus-derived growth factors and fibroblast growth factors. Proc Natl Acad Sci U S A. 1985 Feb; 82(3):805-9.
  235. Chodak GW, Klagsbrun M, Shing YW. Partial characterization of a cell motility factor from human urine. Cancer Res. 1985 Feb; 45(2):690-4.
  236. Shing Y, Folkman J, Haudenschild C, Lund D, Crum R, Klagsbrun M. Angiogenesis is stimulated by a tumor-derived endothelial cell growth factor. J Cell Biochem. 1985; 29(4):275-87.
  237. D'Amore PA, Klagsbrun M. Endothelial cell mitogens derived from retina and hypothalamus: biochemical and biological similarities. J Cell Biol. 1984 Oct; 99(4 Pt 1):1545-9.
  238. Shing YW, Klagsbrun M. Human and bovine milk contain different sets of growth factors. Endocrinology. 1984 Jul; 115(1):273-82.
  239. Shing Y, Folkman J, Sullivan R, Butterfield C, Murray J, Klagsbrun M. Heparin affinity: purification of a tumor-derived capillary endothelial cell growth factor. Science. 1984 Mar 23; 223(4642):1296-9.
  240. Makris A, Klagsbrun MA, Yasumizu T, Ryan KJ. An endogenous ovarian growth factor which stimulates BALB/3T3 and granulosa cell proliferation. Biol Reprod. 1983 Dec; 29(5):1135-41.
  241. Feig LA, Klagsbrun M, Bellvé AR. Mitogenic polypeptide of the mammalian seminiferous epithelium: biochemical characterization and partial purification. J Cell Biol. 1983 Nov; 97(5 Pt 1):1435-43.
  242. Sullivan RC, Shing YW, D'Amore PA, Klagsbrun M. Use of size-exclusion and ion-exchange high-performance liquid chromatography for the isolation of biologically active growth factors. J Chromatogr. 1983 Aug 26; 266:301-11.
  243. Azizkhan J, Sullivan R, Azizkhan R, Zetter BR, Klagsbrun M. Stimulation of increased capillary endothelial cell motility by chondrosarcoma cell-derived factors. Cancer Res. 1983 Jul; 43(7):3281-6.
  244. Hamerman D, Klagsbrun M. Cell interactions in osteoarthritis: proposed role for cartilage-derived growth factor. Trans Assoc Am Physicians. 1983; 96:316-23.
  245. Bekoff MC, Klagsbrun M. Characterization of growth factors in human cartilage. J Cell Biochem. 1982; 20(3):237-45.
  246. Steimer KS, Packard R, Holden D, Klagsbrun M. The serum-free growth of cultured cells in bovine colostrum and in milk obtained later in the lactation period. J Cell Physiol. 1981 Nov; 109(2):223-34.
  247. Steimer KS, Klagsbrun M. Serum-free growth of normal and transformed fibroblasts in milk: differential requirements for fibronectin. J Cell Biol. 1981 Feb; 88(2):294-300.
  248. Klagsbrun M, Smith S. Purification of a cartilage-derived growth factor. J Biol Chem. 1980 Nov 25; 255(22):10859-66.
  249. Feig LA, Bellvé AR, Erickson NH, Klagsbrun M. Sertoli cells contain a mitogenic polypeptide. Proc Natl Acad Sci U S A. 1980 Aug; 77(8):4774-8.
  250. Klagsbrun M. Bovine colostrum supports the serum-free proliferation of epithelial cells but not of fibroblasts in long-term culture. J Cell Biol. 1980 Mar; 84(3):808-14.
  251. Golbus MS, Djalali M, Klagsbrun M, Kaback MM, Levenson RM, Epstein CJ. Stimulation of amniotic fluid cell growth by cartilage growth factor. Am J Med Genet. 1980; 6(2):107-11.
  252. Tapper D, Klagsbrun M, Neumann J. The identification and clinical implications of human breast milk mitogen. J Pediatr Surg. 1979 Dec; 14(6):803-8.
  253. Klagsbrun M, Neumann J, Tapper D. The mitogenic activity of human breast milk. J Surg Res. 1979 Apr; 26(4):417-22.
  254. Klagsbrun M. Large-scale preparation of chondrocytes. Methods Enzymol. 1979; 58:560-4.
  255. Klagsbrun M, Neumann J. The serum-free growth of Balb/c 3T3 cells in medium supplemented with bovine colostrum. J Supramol Struct. 1979; 11(3):349-59.
  256. Klagsbrun M. Human milk stimulates DNA synthesis and cellular proliferation in cultured fibroblasts. Proc Natl Acad Sci U S A. 1978 Oct; 75(10):5057-61.
  257. Klagsbrun M, Davis DI. Substance abuse and family interaction. Fam Process. 1977 Jun; 16(2):149-73.
  258. Klagsbrun M, Langer R, Levenson R, Smith S, Lillehei C. The stimulation of DNA synthesis and cell division in chondrocytes and 3T3 cells by a growth factor isolated from cartilage. Exp Cell Res. 1977 Mar 01; 105(1):99-108.
  259. Scher C, Haudenschild C, Klagsbrun M. The chick chorioallantoic membrane as a model system for the study of tissue invasion by viral transformed cells. Cell. 1976 Jul; 8(3):373-82.
  260. Haudenschild CC, Zahniser D, Folkman J, Klagsbrun M. Human vascular endothelial cells in culture. Lack of response to serum growth factors. Exp Cell Res. 1976 Mar 01; 98(1):175-83.
  261. Klagsbrun M, Knighton D, Folkman J. Tumor angiogenesis activity in cells grown in tissue culture. Cancer Res. 1976 Jan; 36(1):110-4.
  262. Klagsbrun M, Furano AV. Methylated amino acids in the proteins of bacterial and mammalian cells. Arch Biochem Biophys. 1975 Aug; 169(2):529-39.
  263. Klagsbrun M, Farrell PM. The methylation of transfer and ribosomal ribonucleic acid in human fibroblasts: normal methylation of ribonucleic acid in cystic fibrosis. Pediatr Res. 1974 Mar; 8(3):205-11.
  264. Klagsbrun M. An evolutionary study of the methylation of transfer and ribosomal ribonucleic acid in prokaryote and eukaryote organisms. J Biol Chem. 1973 Apr 10; 248(7):2612-20.
  265. Klagsbrun M. Differences in the methylation of transfer ribonucleic acid in vitro by the mitochondrial and cytoplasmic transfer ribonucleic acid methylases of HeLa cells. J Biol Chem. 1973 Apr 10; 248(7):2606-11.
  266. Klagsbrun M. The contrast between the methylation of transfer ribonucleic acid in vivo and in vitro by normal and SV40 transformed 3T3 cells. J Biol Chem. 1972 Dec 10; 247(23):7443-51.
  267. Klagsbrun M. Changes in the methylation of transfer RNA in vaccinia infected HeLa cells. Virology. 1971 Apr; 44(1):153-67.
  268. Adesnik M, Klagsbrun M. Polysomal distribution of late bacteriophage T4 messenger RNA. J Mol Biol. 1970 Nov 28; 54(1):155-8.
  269. Klagsbrun M, Rich A. In vitro synthesis of T4 bacteriophage head protein using polysomes of T4-infected Escherichia coli. J Mol Biol. 1970 Mar; 48(3):421-36.
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