Photo of Harold F. Dvorak,  MD

Harold F. Dvorak, MD

Beth Israel Deaconess Medical Center

Beth Israel Deaconess Medical Center
Phone: (617) 667-8529
Fax: (617) 667-2913

Harold F. Dvorak, MD

Beth Israel Deaconess Medical Center


  • Mallinckrodt Distinguished Professor of Pathology, Pathology, Harvard Medical School
  • Chief, Pathology, Beth Israel Deaconess Medical Center

Research Abstract

Dr. Dvorak's current research interests:

1. Steps and mechanisms of VPF/VEGF-mediated angiogenesis, particularly the role of vascular hyperpermeability in this process.

2. Anatomic (ultrastructural) and signaling pathways of microvascular hyperpermeability in tumor microvessels and in normal microvessels stimulated by VPF/VEGF.

3. Generation of new blood vessels with the properties of mature normal vessels (in contrast to the immature, poorly differentiated vessels induced in tumors, wounds, etc.) as an approach to tissue (heart, legs) ischemia.

4. Vascular targeting as an approach to tumor therapy.


Powered by Harvard Catalyst
  • Visintin A, Knowlton K, Tyminski E, Lin CI, Zheng X, Marquette K, Jain S, Tchistiakova L, Li D, O'Donnell CJ, Maderna A, Cao X, Dunn R, Snyder WB, Abraham AK, Leal M, Shetty S, Barry A, Zawel L, Coyle AJ, Dvorak HF, Jaminet SC. Novel Anti-TM4SF1 Antibody-Drug Conjugates with Activity against Tumor Cells and Tumor Vasculature. Mol Cancer Ther 2015. PubMed
  • Dvorak HF. Tumors: wounds that do not heal-redux. Cancer Immunol Res 2015; 3:1-11. PubMed
  • Lin CI, Merley A, Sciuto TE, Li D, Dvorak AM, Melero-Martin JM, Dvorak HF, Jaminet SC. TM4SF1: a new vascular therapeutic target in cancer. Angiogenesis 2014; 17:897-907. PubMed
  • Sadow PM, Priolo C, Nanni S, Karreth FA, Duquette M, Martinelli R, Husain A, Clohessy J, Kutzner H, Mentzel T, Carman CV, Farsetti A, Henske EP, Palescandolo E, Macconaill LE, Chung S, Fadda G, Lombardi CP, De Angelis AM, Durante O, Parker JA, Pontecorvi A, Dvorak HF, Fletcher C, Pandolfi PP, Lawler J, Nucera C. Role of BRAFV600E in the First Preclinical Model of Multifocal Infiltrating Myopericytoma Development and Microenvironment. Journal of the National Cancer Institute 2014. PubMed
  • Qin L, Zhao D, Xu J, Ren X, Terwilliger EF, Parangi S, Lawler J, Dvorak HF, Zeng H. The vascular permeabilizing factors histamine and serotonin induce angiogenesis through TR3/Nur77 and subsequently truncate it through thrombospondin-1. Blood 2013; 121:2154-64. PubMed
  • Nagy JA, Dvorak HF. Heterogeneity of the tumor vasculature: the need for new tumor blood vessel type-specific targets. Clin Exp Metastasis 2012; 29:657-62. PubMed
  • Hoeppner LH, Phoenix KN, Clark KJ, Bhattacharya R, Gong X, Sciuto TE, Vohra P, Suresh S, Bhattacharya S, Dvorak AM, Ekker SC, Dvorak HF, Claffey KP, Mukhopadhyay D. Revealing the role of phospholipase C硫3 in the regulation of VEGF-induced vascular permeability. Blood 2012; 120:2167-73. PubMed
  • Fu Y, Nagy JA, Brown LF, Shih SC, Johnson P, Chan CK, Dvorak HF, Wight T. Proteolytic Cleavage of Versican and Involvement of ADAMTS-1 in VEGF-A/VPF-Induced Pathological Angiogenesis. J. Histochem. Cytochem. 2011. PubMed
  • Wada Y, Li D, Merley A, Zukauskas A, Aird WC, Dvorak HF, Shih SC. A multi-gene transcriptional profiling approach to the discovery of cell signature markers. Cytotechnology 2010. PubMed
  • Dvorak HF. Vascular permeability to plasma, plasma proteins, and cells: an update. Curr Opin Hematol 2010; 17:225-9. PubMed
  • Nagy JA, Chang SH, Shih SC, Dvorak AM, Dvorak HF. Heterogeneity of the tumor vasculature. Semin Thromb Hemost 2010; 36:321-31. PubMed
  • Chang SH, Feng D, Nagy JA, Sciuto TE, Dvorak AM, Dvorak HF. Vascular permeability and pathological angiogenesis in caveolin-1-null mice. Am J Pathol 2009; 175:1768-76. PubMed
  • Zhang X, Kazerounian S, Duquette M, Perruzzi C, Nagy JA, Dvorak HF, Parangi S, Lawler J. Thrombospondin-1 modulates vascular endothelial growth factor activity at the receptor level. FASEB J 2009; 23:3368-76. PubMed
  • Xue Q,Nagy JA,Manseau EJ,Phung TL,Dvorak HF,Benjamin LE. Rapamycin Inhibition of the Akt/mTOR Pathway Blocks Select Stages of VEGF-A164-Driven Angiogenesis, in Part by Blocking S6Kinase. Arterioscler Thromb Vasc Biol 2009; 29:1172-8. PubMed
  • Chang SH,Kanasaki K,Gocheva V,Blum G,Harper J,Moses MA,Shih SC,Nagy JA,Joyce J,Bogyo M,Kalluri R,Dvorak HF. VEGF-A induces angiogenesis by perturbing the cathepsin-cysteine protease inhibitor balance in venules, causing basement membrane degradation and mother vessel formation. Cancer Res 2009; 69:4537-44. PubMed
  • Shih SC,Zukauskas A,Li D,Liu G,Ang LH,Nagy JA,Brown LF,Dvorak HF. The L6 protein TM4SF1 is critical for endothelial cell function and tumor angiogenesis. Cancer Res 2009; 69:3272-7. PubMed
  • Nagy JA, Benjamin L, Zeng H, Dvorak AM, Dvorak HF. Vascular permeability, vascular hyperpermeability and angiogenesis. Angiogenesis 2008; 11:109-19. PubMed
  • Wirzenius M, Tammela T, Uutela M, He Y, Odorisio T, Zambruno G, Nagy JA, Dvorak HF, Yla-Herttuala S, Shibuya M, Alitalo K. Distinct vascular endothelial growth factor signals for lymphatic vessel enlargement and sprouting. J Exp Med 2007; 204:1431-40. PubMed
  • Carman CV, Sage PT, Sciuto TE, de la Fuente MA, Geha RS, Ochs HD, Dvorak HF, Dvorak AM, Springer TA. Transcellular diapedesis is initiated by invasive podosomes. Immunity 2007; 26:784-97. PubMed
  • Phung TL, Ziv K, Dabydeen D, Eyiah-Mensah G, Riveros M, Sun JF, Monahan-Early R, Shiojima I, Nagy JA, Lin MI, Walsh K, Dvorak AM, Briscoe DM, Neeman M, Sessa WC, Dvorak HF, Benajmin LE. Pathological angiogenesis is induced by sustained AKT signaling and inhibited by Rapamycin. Cancer Cell 2006; In Press:In Press.
  • Zeng H, Dvorak HF, Mukhopadhyay D. Vascular permeability factor (VPF)/vascular endothelial growth factor (VEGF) peceptor-1 down-modulates VPF/VEGF receptor-2-mediated endothelial cell proliferation, but not migration, through phosphatidylinositol 3-kinase-dependent pathways. J Biol Chem 2001; 276:26969-79. PubMed
  • Epstein SE, Kornowski R, Fuchs S, Dvorak HF. Angiogenesis therapy: amidst the hype, the neglected potential for serious side effects. Circulation 2001; 104:115-9. PubMed
  • Basu S, Nagy JA, Pal S, Vasile E, Eckelhoefer IA, Bliss VS, Manseau EJ, Dasgupta PS, Dvorak HF, Mukhopadhyay D. The neurotransmitter dopamine inhibits angiogenesis induced by vascular permeability factor/vascular endothelial growth factor. Nat Med 2001; 7:569-74. PubMed
  • Sundberg C, Nagy JA, Brown LF, Feng D, Eckelhoefer IA, Manseau EJ, Dvorak AM, Dvorak HF. Glomeruloid microvascular proliferation follows adenoviral vascular permeability factor/vascular endothelial growth factor-164 gene delivery. Am J Pathol 2001; 158:1145-60. PubMed
  • Pal S, Iruela-Arispe ML, Harvey VS, Zeng H, Nagy JA, Dvorak HF, Mukhopadhyay D. Retinoic acid selectively inhibits the vascular permeabilizing effect of VPF/VEGF, an early step in the angiogenic cascade. Microvasc Res 2000; 60:112-20. PubMed
  • Brown LF, Dezube BJ, Tognazzi K, Dvorak HF, Yancopoulos GD. Expression of Tie1, Tie2, and angiopoietins 1, 2, and 4 in Kaposi's sarcoma and cutaneous angiosarcoma. Am J Pathol 2000; 156:2179-83. PubMed
  • Pettersson A, Nagy JA, Brown LF, Sundberg C, Morgan E, Jungles S, Carter R, Krieger JE, Manseau EJ, Harvey VS, Eckelhoefer IA, Feng D, Dvorak AM, Mulligan RC, Dvorak HF. Heterogeneity of the angiogenic response induced in different normal adult tissues by vascular permeability factor/vascular endothelial growth factor. Lab Invest 2000; 80:99-115. PubMed
  • Fu Y, Comella N, Tognazzi K, Brown LF, Dvorak HF, Kocher O. Cloning of DLM-1, a novel gene that is up-regulated in activated macrophages, using RNA differential display. Gene 1999; 240:157-63. PubMed
  • Brown LF, Guidi AJ, Schnitt SJ, Van De Water L, Iruela-Arispe ML, Yeo TK, Tognazzi K, Dvorak HF. Vascular stroma formation in carcinoma in situ, invasive carcinoma, and metastatic carcinoma of the breast. Clin Cancer Res 1999; 5:1041-56. PubMed
  • Feng D, Nagy JA, Pyne K, Hammel I, Dvorak HF, Dvorak AM. Pathways of macromolecular extravasation across microvascular endothelium in response to VPF/VEGF and other vasoactive mediators. Microcirculation 1999; 6:23-44. PubMed
  • Vasile E, Qu-Hong , Dvorak HF, Dvorak AM. Caveolae and vesiculo-vacuolar organelles in bovine capillary endothelial cells cultured with VPF/VEGF on floating Matrigel-collagen gels. J Histochem Cytochem 1999; 47:159-67. PubMed
  • Dvorak HF, Nagy JA, Feng D, Brown LF, Dvorak AM. Vascular permeability factor/vascular endothelial growth factor and the significance of microvascular hyperpermeability in angiogenesis. Curr Top Microbiol Immunol 1999; 237:97-132. PubMed
  • Feng D, Nagy JA, Pyne K, Dvorak HF, Dvorak AM. Platelets exit venules by a transcellular pathway at sites of F-met peptide-induced acute inflammation in guinea pigs. Int Arch Allergy Immunol 1998; 116:188-95. PubMed
  • Feng D, Nagy JA, Pyne K, Dvorak HF, Dvorak AM. Neutrophils emigrate from venules by a transendothelial cell pathway in response to FMLP. J Exp Med 1998; 187:903-15. PubMed
  • Mukhopadhyay D, Nagy JA, Manseau EJ, Dvorak HF. Vascular permeability factor/vascular endothelial growth factor-mediated signaling in mouse mesentery vascular endothelium. Cancer Res 1998; 58:1278-84. PubMed
  • Guidi AJ, Schnitt SJ, Fischer L, Tognazzi K, Harris JR, Dvorak HF, Brown LF. Vascular permeability factor (vascular endothelial growth factor) expression and angiogenesis in patients with ductal carcinoma in situ of the breast. Cancer 1997; 80:1945-53. PubMed
  • Feng D, Nagy JA, Hipp J, Pyne K, Dvorak HF, Dvorak AM. Reinterpretation of endothelial cell gaps induced by vasoactive mediators in guinea-pig, mouse and rat: many are transcellular pores. J Physiol 1997; 504 ( Pt 3):747-61. PubMed
  • Pal S, Claffey KP, Dvorak HF, Mukhopadhyay D. The von Hippel-Lindau gene product inhibits vascular permeability factor/vascular endothelial growth factor expression in renal cell carcinoma by blocking protein kinase C pathways. J Biol Chem 1997; 272:27509-12. PubMed
  • Carlson I, Tognazzi K, Manseau EJ, Dvorak HF, Brown LF. Osteopontin is strongly expressed by histiocytes in granulomas of diverse etiology. Lab Invest 1997; 77:103-8. PubMed
  • Watanabe Y, Dvorak HF. Vascular permeability factor/vascular endothelial growth factor inhibits anchorage-disruption-induced apoptosis in microvessel endothelial cells by inducing scaffold formation. Exp Cell Res 1997; 233:340-9. PubMed
  • Watanabe Y, Lee SW, Detmar M, Ajioka I, Dvorak HF. Vascular permeability factor/vascular endothelial growth factor (VPF/VEGF) delays and induces escape from senescence in human dermal microvascular endothelial cells. Oncogene 1997; 14:2025-32. PubMed
  • Detmar M, Brown LF, Berse B, Jackman RW, Elicker BM, Dvorak HF, Claffey KP. Hypoxia regulates the expression of vascular permeability factor/vascular endothelial growth factor (VPF/VEGF) and its receptors in human skin. J Invest Dermatol 1997; 108:263-8. PubMed
  • Feng D, Nagy JA, Hipp J, Dvorak HF, Dvorak AM. Vesiculo-vacuolar organelles and the regulation of venule permeability to macromolecules by vascular permeability factor, histamine, and serotonin. J Exp Med 1996; 183:1981-6. PubMed
  • Dvorak AM, Kohn S, Morgan ES, Fox P, Nagy JA, Dvorak HF. The vesiculo-vacuolar organelle (VVO): a distinct endothelial cell structure that provides a transcellular pathway for macromolecular extravasation. J Leukoc Biol 1996; 59:100-15. PubMed
  • Claffey KP, Brown LF, del Aguila LF, Tognazzi K, Yeo KT, Manseau EJ, Dvorak HF. Expression of vascular permeability factor/vascular endothelial growth factor by melanoma cells increases tumor growth, angiogenesis, and experimental metastasis. Cancer Res 1996; 56:172-81. PubMed
  • Nagy JA, Morgan ES, Herzberg KT, Manseau EJ, Dvorak AM, Dvorak HF. Pathogenesis of ascites tumor growth: angiogenesis, vascular remodeling, and stroma formation in the peritoneal lining. Cancer Res 1995; 55:376-85. PubMed
  • Dvorak HF, Nagy JA, Berse B, Brown LF, Yeo KT, Yeo TK, Dvorak AM, van de Water L, Sioussat TM, Senger DR. Vascular permeability factor, fibrin, and the pathogenesis of tumor stroma formation. Ann N Y Acad Sci 1992; 667:101-11. PubMed
  • Kohn S, Nagy JA, Dvorak HF, Dvorak AM. Pathways of macromolecular tracer transport across venules and small veins. Structural basis for the hyperpermeability of tumor blood vessels. Lab Invest 1992; 67:596-607. PubMed
  • Brown LF, Yeo KT, Berse B, Yeo TK, Senger DR, Dvorak HF, van de Water L. Expression of vascular permeability factor (vascular endothelial growth factor) by epidermal keratinocytes during wound healing. J Exp Med 1992; 176:1375-9. PubMed
  • Senger DR, Connolly DT, Van de Water L, Feder J, Dvorak HF. Purification and NH2-terminal amino acid sequence of guinea pig tumor-secreted vascular permeability factor. Cancer Res 1990; 50:1774-8. PubMed
  • Dvorak HF. Tumors: wounds that do not heal. Similarities between tumor stroma generation and wound healing. N Engl J Med 1986; 315:1650-9. PubMed
  • Senger DR, Galli SJ, Dvorak AM, Perruzzi CA, Harvey VS, Dvorak HF. Tumor cells secrete a vascular permeability factor that promotes accumulation of ascites fluid. Science 1983; 219:983-5. PubMed
  • Dvorak HF, Quay SC, Orenstein NS, Dvorak AM, Hahn P, Bitzer AM, Carvalho AC. Tumor shedding and coagulation. Science 1981; 212:923-4. PubMed
  • Dvorak HF, Dvorak AM, Manseau EJ, Wiberg L, Churchill WH. Fibrin gel investment associated with line 1 and line 10 solid tumor growth, angiogenesis, and fibroplasia in guinea pigs. Role of cellular immunity, myofibroblasts, microvascular damage, and infarction in line 1 tumor regression. J Natl Cancer Inst 1979; 62:1459-72. PubMed