Section: Research

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Nathan Lawson, Ph.D.

Academic Role: Associate Professor

Faculty Appointment(s) In:
   Program in Gene Function and Expression
   Program in Molecular Medicine

Other Affiliation(s):
   Interdisciplinary Graduate Program

Determining the Signals Responsible for Blood Vessel Development using Zebrafish

The formation of new blood vessels is required for proper development of the embryonic circulatory system and is an important step in the progression of many diseases, including cancer. My laboratory studies the development of blood vessels using the zebrafish as a model system. In particular we are interested in the role of two signaling pathway - the vascular endothelial growth factor (Vegf) and Notch pathways - and their role in governing various aspects of angiogenesis. Among the questions we are interested in are: what is the role of differentiation during blood vessel development? Why do endothelial cells in different vessels display distinct behaviors, patterns of gene expression, and responses to growth factors? How do these differences impact the normal development of the circulatory system? How do the Vegf and Notch signaling pathways act to govern blood vessel formation? Finally, how can we translate our studies to other models and to relevant clinical settings?

We are able to address many of these questions in living embryos thanks to the benefits of the zebrafish model. Their embryos are transparent and develop externally. In addition, their early development is quite rapid - by 36 hours post fertilization they have a functional circulatory network, complete with beating heart, patent blood vessels, and flowing blood. We have also generated a number of transgenic zebrafish lines that allow us to visualize blood vessels in vivo using time lapse analysis. Additionally, we can easily manipulate signaling pathways through injection of antisense oligonucleotides and can use forward genetic approaches (e.g. screens) to identify mutants that affect various aspects of blood vessel development. Most importantly, the signals that govern embryonic blood vessel development are the same as those that act during angiogenesis associated numerous disease states. Also, these signals have been largely conserved throughout evolution - many of our studies have been paralleled with similar findings in mice. Therefore, the use of the zebrafish to analyze this process will provide important insight onto the process of angiogenesis in other models.

For much more information on the work in my laboratory, please see our lab website at http://lawsonlab.umassmed.edu

Office: 617
Phone: 508-856-1177
E-mail: Nathan.Lawson@umassmed.edu
Keywords: Signal Transduction, Developmental Biology

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