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


hdvorak@bidmc.harvard.edu

Harold F. Dvorak, MD

Beth Israel Deaconess Medical Center

EDUCATIONAL TITLES

  • 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.

Publications from Harvard Catalyst Profiles

Powered by Harvard Catalyst
  • Dvorak HF. Tumors: Wounds That Do Not Heal-A Historical Perspective with a Focus on the Fundamental Roles of Increased Vascular Permeability and Clotting. Semin Thromb Hemost 2019. PubMed
  • Sitohy B, Chang S, Sciuto TE, Masse E, Shen M, Kang PM, Jaminet SC, Benjamin LE, Bhatt RS, Dvorak AM, Nagy JA, Dvorak HF. Early Actions of Anti-Vascular Endothelial Growth Factor/Vascular Endothelial Growth Factor Receptor Drugs on Angiogenic Blood Vessels. Am J Pathol 2017; 187:2337-2347. PubMed
  • Bridgeman VL, Vermeulen PB, Foo S, Bilecz A, Daley F, Kostaras E, Nathan MR, Wan E, Frentzas S, Schweiger T, Hegedus B, Hoetzenecker K, Renyi-Vamos F, Kuczynski EA, Vasudev NS, Larkin J, Gore M, Dvorak HF, Paku S, Kerbel RS, Dome B, Reynolds AR. Vessel co-option is common in human lung metastases and mediates resistance to anti-angiogenic therapy in preclinical lung metastasis models. J Pathol 2016. PubMed
  • Uhlik MT, Liu J, Falcon BL, Iyer S, Stewart J, Celikkaya H, O'Mahony M, Sevinsky C, Lowes C, Douglass L, Jeffries C, Bodenmiller D, Chintharlapalli S, Fischl A, Gerald D, Xue Q, Lee JY, Santamaria-Pang A, Al-Kofahi Y, Sui Y, Desai K, Doman T, Aggarwal A, Carter JH, Pytowski B, Jaminet SC, Ginty F, Nasir A, Nagy JA, Dvorak HF, Benjamin LE. Stromal-Based Signatures for the Classification of Gastric Cancer. Cancer Res 2016; 76:2573-86. PubMed
  • Sciuto TE, Merley A, Lin CI, Richardson D, Liu Y, Li D, Dvorak AM, Dvorak HF, Jaminet SC. Intracellular distribution of TM4SF1 and internalization of TM4SF1-antibody complex in vascular endothelial cells. Biochem Biophys Res Commun 2015; 465:338-43. PubMed
  • 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 Cβ3 in the regulation of VEGF-induced vascular permeability. Blood 2012; 120:2167-73. PubMed
  • Fu Y, Nagy JA, Brown LF, Shih SC, Johnson PY, Chan CK, Dvorak HF, Wight TN. 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
  • 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
  • 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
  • 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.
  • Connor Y, Tekleab S, Nandakumar S, Walls C, Tekleab Y, Husain A, Gadish O, Sabbisetti V, Kaushik S, Sehrawat S, Kulkarni A, Dvorak H, Zetter B, R Edelman E, Sengupta S. Physical nanoscale conduit-mediated communication between tumour cells and the endothelium modulates endothelial phenotype. Nat Commun ; 6:8671. PubMed
  • Dvorak HF. Tumor Stroma, Tumor Blood Vessels, and Antiangiogenesis Therapy. Cancer J ; 21:237-43. PubMed
Hide