Harold F. Dvorak, M.D.
Professor of Pathology
Beth Israel Deaconess Medical Center
Department of Pathology
330 Brookline Avenue, RN-227C
Boston, MA 02215
Residency training in Pathology at MGH; two years as a post-doc at NIH; 16 years as Staff Pathologist, MGH; 27 years as Chair of Pathology at BIH and then BIDMC; now doing full time research in vascular biology.
Research Interests: Vascular Permeability, Angiogenesis, Arteriogenesis, Venogenesis, Lymphangiogenesis (Vascular Permeability & Angiogenesis)
Basic Research - - Tumors induce a heterogeneous neovascular response that includes angiogenesis, arteriogenesis, venogenesis and lymphangiogenesis; we have been able to mimic this response using an adenoviral vector expressing VEGF-A (Ad-VEGF-A164). Whether induced by tumors or by Ad-VEGF-A164, angiogenesis leads to the formation of at least four types of morphologically and functionally distinct blood vessels from preexisting venules: mother vessels (MV) form initially and subsequently differentiate into capillaries, glomeruloid microvascular proliferations (GMP) and vascular malformations (VM). Feeder arteries (FA), draining veins (DV) and giant lymphatics develop simultaneously from preexisting arteries, veins and lymphatics. Ad-VEGF-A164 offers the advantage that it induces the formation of each vessel type in large numbers, with predictable kinetics, and without the complicating presence of tumor cells. My major research interests are as follows: 1. Elucidate the mechanisms by which VEGF-secreting tumors induce the formation of new blood vessels and lymphatics. 2. Define the characteristics of these newly formed vessels. 3. Determine their response to anti-angiogenic therapy. 4. Identify new molecules on tumor vascular endothelium that may serve as therapeutic targets. 5. Elucidate the mechanisms of vascular permeability to macromolecules and cells.
New and Noteworthy Publications:
Nagy, J.A., Benjamin, L., Zeng, H., Dvorak, A.M., and Dvorak, H.F. (2008) Vascular permeability, vascular hyperpermeability and angiogenesis. Angiogenesis 11, p109. This paper distinguishes among the three types of vascular permeability to circulating macromolecultes, basal vascular permeability (BVP), and the increased permeability induced by VEGF and other vascular permeability factors: the acute vascular permeability (AVH) of acute inflammation and the chronic vascular hyperpermeability (CVH) that is found in tumors, wound healing and chronic inflammatory diseases. Venules are the site of AVH and the pathway is to a large extent trans-endothelial cell via the vesiculo-vacuolar organelle (VVO). CVH is largely mediated by MV and glomeruloid microvascular proliferations (GMP).