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Donald Senger Lab

Our laboratory is focused on defining the signaling pathways and cytoskeletal-related mechanisms that control the organization of endothelial cells into new blood vessels, with the overall goal of identifying new therapeutic strategies for inhibiting and promoting neovascularization. Key aspects of capillary morphogenesis are mimicked by endothelial cells in vitro when they are stimulated by three dimensional collagen I In vitro, and we have identified several signaling pathways and effectors that are activated by collagen I-stimulation which are critical for capillary morphogenesis. These include integrin-mediated suppression of protein kinase A activity and marked increases in activities of the GTPase Rho and Src family kinases, all of which contribute to actin polymerization, stress fiber formation, and endothelial cell contractility and morphogenesis. Similarly, in vivo, we have shown that RhoA serves a critical function in regulating capillary morphogenesis and that modest suppression of RhoA activity markedly impairs endothelial cell organization and angiogenesis. By contrast, increased RhoA activity promotes capillary morphogenesis and promotes functional neovascularization. With retroviral-based approaches, we now are defining the specific functions of other downstream effectors of collagen I signaling in endothelial cells with the goal of identifying additional molecular targets for regulating capillary morphogenesis and angiogenesis in vivo.

Selected Recent Publications

Hoang MV, Whelan MC, Senger DR. Rho activity critically and selectively regulates endothelial cell organization during angiogenesis. Proc Natl Acad Sci USA 2004, 101: 1874-1879.

Liu Y, Senger DR. Matrix-specific activation of Src and Rho initiates capillary morphogenesis of endothelial cells. FASEB J. 2004, 18: 457-468.

Hoang MV, Senger DR, In vivo and in vitro models of mammalian angiogenesis. In: Methods in Molecular Biology series: "Cell Migration in Development," Human Press, 2004, pp 269-285 .

Contact Information

Donald Senger
Pathology
Beth Israel Deaconess Medical Center
RN 280E
330 Brookline Avenue
Boston, MA 02215
617-667-5766
617-667-3591
dsenger@bidmc.harvard.edu