Janice A. Nagy, Ph.D.
Principal Associate in Pathology
Beth Israel Deaconess Medical Center
Harvard Medical School

330 Brookline Avenue, RN-280F
Boston, MA 02215
Office: 617-667-5768
Fax: 617-667-3591


Janice Nagy earned a Ph.D. in Biophysical Chemistry from Cornell University, Ithaca, NY in 1982. She then performed post-doctoral work at Harvard Medical School with Timothy A. Springer. In 1983 Dr. Nagy joined the Department of Pathology at Beth Israel Deaconess Medical Center as an Instructor and was promoted to Assistant Professor in 1990. In 1999 D. Nagy became a Principal Associate in Pathology and is currently a member of the CVBR.

Research Interests: VEGF and the Pathological Vascular Phenotype


Basic Research - The main focus of my research is to understand the role of a major tumor-secreted cytokine, Vascular Endothelial Growth Factor (VEGF-A), in the induction the pathological vascular phenotype. Whereas normal angiogenesis results in a well-ordered and highly functional vascular network, the pathological angiogenesis that is a conspicuous feature of tumor growth, ischemic diseases, and chronic inflammation, is characterized by vessels with aberrant angioarchitecture and compromised barrier function, and typically results from the unbalanced expression of VEGF-A.

Pathological Angiogenesis. - Using an adenoviral vector strategy to overexpress VEGF-A in a variety of normal mouse tissues, we have identified six unique types of tumor surrogate blood vessels that closely resemble the blood vessels found in VEGF-A-expressing tumors. We have characterized the temporal, architectural and permeability properties of these vessels, and current studies are designed to investigate the molecular properties of these various vessel types to identify new targets for therapeutic intervention. Future studies will use our adenoviral approach to compare and contrast the distinctive characteristics of the VEGF-A-induced neovasculature with those elicited by other proangiogenic growth factors (e.g., FGF-2 and PlGF). Such an analysis will lead to a better understanding of pathological angiogenesis and will hopefully lead to new approaches to anti-angiogenic therapy.

Pathological Lymphangiogenesis. - In parallel studies, we made the unanticipated finding that VEGF-A can also induce a strong lymphangiogenic response. We found that the new "giant" lymphatics generated by VEGF-A overexpression were structurally and functionally abnormal: greatly enlarged with incompetent valves, sluggish flow, and delayed lymph clearance. They closely resembled the large lymphatics found in lymphangiomas and lymphatic malformations. These “giant” lymphatics, once formed, became VEGF-A independent and persisted indefinitely, long after VEGF-A expression ceased. These findings raise the possibility that similar, abnormal lymphatics develop in other pathologies in which VEGF-A is overexpressed, e.g., malignant tumors and chronic inflammation. Our current focus in this area is: 1) to gain insight into the specific VEGF/VEGF receptor signal transduction pathways responsible for this observed lymphatic vessel hyperplasia in vivo; and 2) to use laser capture microdissection and microarray analysis to further characterize the gene expression pattern of these “giant” lymphatics.

New and Noteworthy Publications:

Sitohy B, Nagy JA, Jaminet SC, Dvorak HF. (2011) Cancer Res. 71:7021-7028. Tumor surrogate blood vessel subtypes exhibit differential susceptibility to anti-VEGF therapy.  This paper defines the susceptibility of different pathological blood vessel subtypes to anti-VEGF therapy with VEGF Trap, offering a possible explanation for the limited effectiveness of anti-VEGF-A/VEGFR treatment of human cancers.

Nagy JA, Chang SH, Shih SC, Dvorak AM, Dvorak HF. (2010) Semin Thromb Hemost. 36:321-331. Heterogeneity of the tumor vasculature. This review describes the six distinctly different tumor vessel types found in tumors. Four of the six vessel types (mother vessels, capillaries, glomeruloid microvascular proliferations, and vascular malformations) develop from preexisting normal venules and capillaries by angiogenesis. The two remaining vessel types (feeder arteries and draining veins) develop from arterio-venogenesis. All six of these tumor vessel types can be induced to form sequentially in normal mouse tissues by an adenoviral vector expressing vascular endothelial growth factor (VEGF)-A164 as described in Nagy JA, et al (2008) Methods Enzymol. 444:43-64.

Xue Q, Nagy JA, Manseau EJ, Phung TL, Dvorak HF, Benjamin LE. (2009) Arterioscler Thromb Vasc Biol. 8:1172-1178. Rapamycin inhibition of the Akt/mTOR pathway blocks select stages of VEGF-A164-driven angiogenesis, in part by blocking S6Kinase. This paper determined that rapamycin potently inhibited early and mid stages of VEGF-A(164)-driven pathological angiogenesis, but not late-stage pathological angiogenesis or lymphangiogenesis.

Nagy JA, Feng D, Vasile E, Wong WH, Shih SC, Dvorak AM, Dvorak HF. Permeability properties of tumor surrogate blood vessels induced by VEGF-A. (2006) Lab Invest. 86:767-80.This study analyzes the permeability properties of the abnormal vessels generated by overexpression of VEGF-A and identifies which vessel types are permeable to plasma and plasma proteins that together account for the resulting edema characteristic of pathological angiogenesis.
Nagy JA, Vasile E, Feng D, Sundberg C, Brown LF, Detmar MJ, Lawitts JA, Benjamin L, Tan X, Manseau EJ, Dvorak AM, Dvorak HF. Vascular permeability factor/vascular endothelial growth factor induces lymphangiogenesis as well as angiogenesis. (2002) J. Exp Med. 196:1497-506.This study was one of the first to demonstrate that overexpression of VEGF-A induces lymphangiogenesis that results in the formation of lymphatic vessels that are structurally and functionally abnormal.