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Unraveling the molecular regulators of VEGFC - Dr. Batya Cohen

The focus of this work is to reveal novel molecular pathways and microenvironmental states that govern blood and lymph vessels formation. Vascular endothelial growth factor C (VEGFC) was identified as one of the major regulators of these processes we are trying to uncover the molecular mechanisms governing its regulation.

To accomplish this we use a combination of in-silico analysis of VEGFC promoter region, and automated high content screening of small molecule libraries. The putative modulators are evaluated for their role in the regulation of VEGFC expression throughout embryogenesis using the zebrafish model (Fig1, in collaboration with Dr. Karina Yaniv) and during tumor progression, using a variety of mouse tumor models (Fig 2).

Using these approaches we have discovered few novel modulators of VEGFC activity. Recently, lens epithelium-derived growth factor (LEDGF/p75) was found to activate VEGFC expression in xenografts tumor mice models in response to diverse microenvironmental stress signals and gonadotropin stimulation (Cohen B., et al. 2009 and Sapoznik S., et al. 2009). Assessment of the role of additional modulators that may augment or suppress angiogenesis and lymphangiogenesis is now in progress.




Figure 1 | Confocal imaging of a the vasculature of a transgenic Tg(fli1eGFP)yz:Lyve1-DsRed zebrafish embryo at day 4dpf. Blood vessels in gree, lymphatic vessels in red.





Figure 2 | Imaging of a xenograft tumor produced in a window chamber. Tumor in red, blood vessels in green, lymphatic in blue.