Photo of Joyce E. Bischoff,  PhD

Joyce E. Bischoff, PhD

Boston Children's Hospital

Boston Children's Hospital
Phone: (617) 919-2192
Fax: (617) 730-0231


joyce.bischoff@childrens.harvard.edu

Joyce E. Bischoff, PhD

Boston Children's Hospital

EDUCATIONAL TITLES

  • Professor, Surgery, Harvard Medical School
  • Research Associate, Surgery, Boston Children's Hospital
  • Principal Investigator, Surgery and Vascular Biology Program, Boston Children's Hospital

Research Abstract

Hemangioma is a tumor of endothelial cells that occurs in infants. These tumors can grow rapidly, causing organ damage and disfigurement and even threatening life. However, a fascinating aspect is that hemangiomas regress over the course of several years, beginning at one year of age. In my laboratory, we are elucidating the cellular and molecular mechanisms that drive this uncontrolled growth and the spontaneous regression. Recently, we identified endothelial progenitor cells in proliferating hemangiomas – the first demonstration of these cells in a human vascular tumor.

We are also working on how normal endothelial progenitors in blood might be used for cardiovascular repair and tissue-engineering. In a sheep model, we showed that autologous endothelial progenitor cells can be isolated from 15-20 milliliters of peripheral blood and used to create small diameter blood vessels. We also envision the use of blood-derived endothelial progenitors to repair or replace cardiac valves. To pursue this, we are studying growth and differentiation pathways in normal cardiac valve endothelium. Two of our studies have shown that valve endothelial cells from adult tissue can recapitulate processes that occur during valve development. These pathways involve TGF-β and VEGF signaling. We hypothesize that endothelial progenitors, expanded ex vivo, can be induced to behave as valve endothelial cells and thereby manipulated, via tissue engineering processes, to create viable long-lived tissue valve substitutes.

Publications

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  • Ye X, Abou-Rayyah Y, Bischoff J, Ritchie A, Sebire NJ, Watts P, Churchill AJ, Bates DO. Altered ratios of pro- and anti-angiogenic VEGF-A variants and pericyte expression of DLL4 disrupt the vascular maturation in infantile haemangioma. J Pathol 2016. PubMed
  • Dal-Bianco JP, Aikawa E, Bischoff J, Guerrero JL, Hjortnaes J, Beaudoin J, Szymanski C, Bartko PE, Seybolt MM, Handschumacher MD, Sullivan S, Garcia ML, Mauskapf A, Titus JS, Wylie-Sears J, Irvin WS, Chaput M, Messas E, Hagège AA, Carpentier A, Levine RA, . Myocardial Infarction Alters Adaptation of the Tethered Mitral Valve. J Am Coll Cardiol 2016; 67:275-87. PubMed
  • Smadja DM, Levy M, Huang L, Rossi E, Blandinières A, Israel-Biet D, Gaussem P, Bischoff J. Treprostinil indirectly regulates endothelial colony forming cell angiogenic properties by increasing VEGF-A produced by mesenchymal stem cells. Thromb Haemost 2015; 114:735-47. PubMed
  • Couto JA, Huang L, Vivero MP, Kamitaki N, Maclellan RA, Mulliken JB, Bischoff J, Warman ML, Greene AK. Endothelial Cells from Capillary Malformations are Enriched for Somatic GNAQ Mutations. Plast Reconstr Surg 2015. PubMed
  • Boscolo E, Limaye N, Huang L, Kang KT, Soblet J, Uebelhoer M, Mendola A, Natynki M, Seront E, Dupont S, Hammer J, Legrand C, Brugnara C, Eklund L, Vikkula M, Bischoff J, Boon LM. Rapamycin improves TIE2-mutated venous malformation in murine model and human subjects. J Clin Invest 2015; 125:3491-504. PubMed
  • 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-α-lysophosphatidylinositol, mediates ovarian carcinoma cell-induced angiogenesis. Br J Pharmacol 2015. PubMed
  • Allen P, Kang KT, Bischoff J. Rapid onset of perfused blood vessels after implantation of ECFCs and MPCs in collagen, PuraMatrix and fibrin provisional matrices. 2015. PubMed
  • 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; 18:151-62. PubMed
  • Jia D, Huang L, Bischoff J, Moses MA. The endogenous zinc finger transcription factor, ZNF24, modulates the angiogenic potential of human microvascular endothelial cells. FASEB J. 2015; 29:1371-82. PubMed
  • Shapero K, Wylie-Sears J, Levine RA, Mayer JE, Bischoff J. Reciprocal interactions between mitral valve endothelial and interstitial cells reduce endothelial-to-mesenchymal transition and myofibroblastic activation. J Mol Cell Cardiol 2015; 80:175-85. PubMed
  • 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 2014. PubMed
  • Smadja DM, Dorfmüller P, Guerin CL, Bieche I, Badoual C, Boscolo E, Kambouchner M, Cazes A, Mercier O, Humbert M, Gaussem P, Bischoff J, Israël-Biet D. Cooperation between human fibrocytes and endothelial colony-forming cells increases angiogenesis via the CXCR4 pathway. Thromb Haemost 2014; 112:1002-13. PubMed
  • Wylie-Sears J, Levine RA, Bischoff J. Losartan inhibits endothelial-to-mesenchymal transformation in mitral valve endothelial cells by blocking transforming growth factor-β-induced phosphorylation of ERK. Biochem Biophys Res Commun 2014; 446:870-5. PubMed
  • Smadja DM, Guerin CL, Boscolo E, Bieche I, Mulliken JB, Bischoff J. α6-Integrin is required for the adhesion and vasculogenic potential of hemangioma stem cells. Stem Cells 2014; 32:684-93. PubMed
  • Gelfand MV, Hagan N, Tata A, Oh WJ, Lacoste B, Kang KT, Kopycinska J, Bischoff J, Wang JH, Gu C. Neuropilin-1 functions as a VEGFR2 co-receptor to guide developmental angiogenesis independent of ligand binding. Elife 2014; 3:e03720. PubMed
  • Kang KT, Coggins M, Xiao C, Rosenzweig A, Bischoff J. Human vasculogenic cells form functional blood vessels and mitigate adverse remodeling after ischemia reperfusion injury in rats. Angiogenesis 2013. PubMed
  • Boscolo E, Mulliken JB, Bischoff J. Pericytes from infantile hemangioma display proangiogenic properties and dysregulated angiopoietin-1. Arterioscler Thromb Vasc Biol 2013; 33:501-9. PubMed
  • Smadja DM, Mulliken JB, Bischoff J. E-selectin mediates stem cell adhesion and formation of blood vessels in a murine model of infantile hemangioma. Am J Pathol 2012; 181:2239-47. PubMed
  • Stiles J, Amaya C, Pham R, Rowntree RK, Lacaze M, Mulne A, Bischoff J, Kokta V, Boucheron LE, Mitchell DC, Bryan BA. Propranolol treatment of infantile hemangioma endothelial cells: A molecular analysis. Exp Ther Med 2012; 4:594-604. PubMed
  • Kang KT, Allen P, Bischoff J. Bioengineered human vascular networks transplanted into secondary mice reconnect with the host vasculature and re-establish perfusion. Blood 2011; 118:6718-21. PubMed
  • Bischoff J, Aikawa E. Progenitor cells confer plasticity to cardiac valve endothelium. J Cardiovasc Transl Res 2011. PubMed
  • Greenberger S, Yuan S, Walsh LA, Boscolo E, Kang KT, Matthews B, Mulliken JB, Bischoff J. Rapamycin suppresses self-renewal and vasculogenic potential of stem cells isolated from infantile hemangioma. J Invest Dermatol 2011. PubMed
  • Boscolo E, Mulliken JB, Bischoff J. VEGFR-1 mediates endothelial differentiation and formation of blood vessels in a murine model of infantile hemangioma. Am J Pathol 2011. PubMed
  • Boscolo E, Stewart CL, Greenberger S, Wu JK, Durham JT, Herman IM, Mulliken JB, Kitajewski J, Bischoff J. JAGGED1 signaling regulates hemangioma stem cell-to-pericyte/vascular smooth muscle cell differentiation. Arterioscler Thromb Vasc Biol 2011; 31:2181-92. PubMed
  • Greenberger S, Bischoff J. Infantile hemangioma-mechanism(s) of drug action on a vascular tumor. Cold Spring Harb Perspect Med 2012; 1:a006460. PubMed
  • Allen P, Melero-Martin J, Bischoff J. Type I collagen, fibrin and PuraMatrix matrices provide permissive environments for human endothelial and mesenchymal progenitor cells to form neovascular networks. 2011; 5:e74-86. PubMed
  • Wylie-Sears J, Aikawa E, Levine RA, Yang JH, Bischoff J. Mitral valve endothelial cells with osteogenic differentiation potential. Arterioscler Thromb Vasc Biol 2011; 31:598-607. PubMed
  • Allen P, Melero-Martin J, Bischoff J. Type I collagen, fibrin and PuraMatrix matrices provide permissive environments for human endothelial and mesenchymal progenitor cells to form neovascular networks. 2011. PubMed
  • Greenberger S, Adini I, Boscolo E, Mulliken JB, Bischoff J. Targeting NF-虜B in infantile hemangioma-derived stem cells reduces VEGF-A expression. Angiogenesis 2010; 13:327-35. PubMed
  • Melero-Martin J, De Obaldia ME, Allen P, Dudley AC, Klagsbrun M, Bischoff J. Host myeloid cells are necessary for creating bio-engineered human vascular networks in vivo. Tissue Eng Part A 2010; 16:2457-66. PubMed
  • Hjortnaes J, Gottlieb D, Figueiredo JL, Melero-Martin J, Kohler RH, Bischoff J, Weissleder R, Mayer J, Aikawa E. Intravital Molecular Imaging of Small-Diameter Tissue-Engineered Vascular Grafts: A Feasibility Study. 2010; 16:597-607. PubMed
  • Greenberger S, Boscolo E, Adini I, Mulliken JB, Bischoff J. Corticosteroid suppression of VEGF-A in infantile hemangioma-derived stem cells. N Engl J Med 2010; 362:1005-13. PubMed
  • Wu JK, Adepoju O, De Silva D, Baribault K, Boscolo E, Bischoff J, Kitajewski J. A switch in Notch gene expression parallels stem cell to endothelial transition in infantile hemangioma. Angiogenesis 2010; 13:15-23. PubMed
  • Jang GH, Park IS, Yang JH, Bischoff J, Lee YM. Differential functions of genes regulated by VEGF-NFATc1 signaling pathway in the migration of pulmonary valve endothelial cells. FEBS Lett 2009; 584:141-6. PubMed
  • Elmasri H, Karaaslan C, Teper Y, Ghelfi E, Weng M, Ince TA, Kozakewich H, Bischoff J, Cataltepe S. Fatty acid binding protein 4 is a target of VEGF and a regulator of cell proliferation in endothelial cells. FASEB J 2009; 23:3865-73. PubMed
  • Dal-Bianco JP, Aikawa E, Bischoff J, Guerrero JL, Handschumacher MD, Sullivan S, Johnson B, Titus JS, Iwamoto Y, Wylie-Sears J, Levine RA, Carpentier A. Active adaptation of the tethered mitral valve: insights into a compensatory mechanism for functional mitral regurgitation. Circulation 2009; 120:334-42. PubMed
  • Ignatov A, Hoffman O, Smith B, Fahlke J, Peters B, Bischoff J, Costa SD. An 11-year retrospective study of totally implanted central venous access ports: Complications and patient satisfaction. Eur J Surg Oncol 2009; 35:241-6. PubMed
  • Boscolo E, Bischoff J. Vasculogenesis in infantile hemangioma. Angiogenesis 2009; 12:197-207. PubMed
  • Yang JH, Wylie-Sears J, Bischoff J. Opposing actions of Notch1 and VEGF in post-natal cardiac valve endothelial cells. Biochem Biophys Res Commun 2008; 374:512-6. PubMed
  • Dudley AC,Khan ZA,Shih SC,Kang SY,Zwaans BM,Bischoff J,Klagsbrun M. Calcification of multipotent prostate tumor endothelium. Cancer Cell 2008; 14:201-11. PubMed
  • Melero-Martin JM,De Obaldia ME,Kang SY,Khan ZA,Yuan L,Oettgen P,Bischoff J. Engineering robust and functional vascular networks in vivo with human adult and cord blood-derived progenitor cells. Circ Res 2008; 103:194-202. PubMed
  • Khan ZA,Boscolo E,Picard A,Psutka S,Melero-Martin JM,Bartch TC,Mulliken JB,Bischoff J. Multipotential stem cells recapitulate human infantile hemangioma in immunodeficient mice. J Clin Invest 2008; 118:2592-9. PubMed
  • Picard A, Boscolo E, Khan ZA, Bartch TC, Mulliken JB, Vazquez MP, Bischoff J. IGF-2 and FLT-1/VEGF-R1 mRNA levels reveal distinctions and similarities between congenital and common infantile hemangioma. Pediatr Res 2008; 63:263-7. PubMed
  • Bischoff J, Griffioen AW. In memoriam Dr. Judah Folkman. Angiogenesis 2008; 11:1-2. PubMed
  • Malumbres M, Pevarello P, Barbacid M, Bischoff JR. CDK inhibitors in cancer therapy: what is next? Trends Pharmacol Sci 2007; 29:16-21. PubMed
  • Mulliken JB, Bischoff J, Kozakewich HP. Multifocal rapidly involuting congenital hemangioma: a link to chorangioma. Am J Med Genet A 2007; 143:3038-46. PubMed
  • Wu X, Lensch MW, Wylie-Sears J, Daley GQ, Bischoff J. Hemogenic endothelial progenitor cells isolated from human umbilical cord blood. Stem Cells 2007; 25:2770-6. PubMed
  • Melero-Martin JM, Khan ZA, Picard A, Wu X, Paruchuri S, Bischoff J. In vivo vasculogenic potential of human blood-derived endothelial progenitor cells. Blood 2007; 109:4761-8. PubMed
  • Paruchuri S, Yang JH, Aikawa E, Melero-Martin JM, Khan ZA, Loukogeorgakis S, Schoen FJ, Bischoff J. Human pulmonary valve progenitor cells exhibit endothelial/mesenchymal plasticity in response to vascular endothelial growth factor-A and transforming growth factor-beta2. Circ Res 2006; 99:861-9. PubMed
  • Khan ZA, Melero-Martin JM, Wu X, Paruchuri S, Boscolo E, Mulliken JB, Bischoff J. Endothelial progenitor cells from infantile hemangioma and umbilical cord blood display unique cellular responses to endostatin. Blood 2006; 108:915-21. PubMed
  • Yu Y, Fuhr J, Boye E, Gyorffy S, Soker S, Atala A, Mulliken JB, Bischoff J. Mesenchymal stem cells and adipogenesis in hemangioma involution. Stem Cells 2006; 24:1605-12. PubMed
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