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program in gene function and expression : faculty

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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

Recent Publications

Parsons, M. J., Pisharath, H., Yusuff, S., Moore, J. C., Siekmann, A. F., Lawson, N. and Leach, S. D. (2009) Notch-responsive cells initiate the secondary transition in larval zebrafish pancreas. Mech. Dev., 126: 898-912.

Siekmann, A. F., Standley, C., Fogarty, K. E., Wolfe, S. A. and Lawson, N. D. (2009) Chemokine signaling guides regional patterning of the first embryonic artery. Genes Dev., 23: 2272-2277.

Covassin, L. D., Siekmann, A. F., Kacergis, M. C., Laver, E., Moore, J. C., Villefranc, J. A., Weinstein, B. M. and Lawson, N. D. (2009) A genetic screen for vascular mutants in zebrafish reveals dynamic roles for Vegf/Plcg1 signaling during artery development. Dev. Biol., 329: 212-226.

Meng, X., Noyes, M. B., Zhu, L. J., Lawson, N. D. and Wolfe, S. A. (2008) Targeted gene inactivation in zebrafish using engineered zinc-finger nucleases. Nat. Biotechnol., 26: 695-701.

Villefranc, J. A., Amigo, J. and Lawson, N. D. (2007) Gateway compatible vectors for analysis of gene function in the zebrafish. Dev. Dyn., 236: 3077-3087.

Siekmann, A. F. and Lawson, N. D. (2007) Notch signalling limits angiogenic cell behaviour in developing zebrafish arteries. Nature, 445: 781-784.

Covassin, L., Amigo, J. D., Suzuki, K., Teplyuk, V., Staubhaar, J., and Lawson, N. D. (2006) Global analysis of hematopoietic and vascular endothelial gene expression by tissue specific microarray profiling in zebrafish. Dev. Biol., 299: 551-562.

Covassin, L. D., Villefranc, J. A., Kacergis, M.C., Weinstein, B. M., and Lawson, N. D. (2006) Distinct genetic interactions between multiple Vegf receptors are required for development of different blood vessel types in zebrafish. Proc. Natl. Acad. Sci. USA., 103: 6554-6559.

Huang, C. C., Lawson, N. D., Weinstein, B. M., and Johnson, S. L. (2003) reg6 is required for branching morphogenesis during blood vessel regeneration in zebrafish caudal fins. Developmental Biology, 264: 263-274.

Isogai, S., Lawson, N. D., Torrealday, S., Horiguchi, M., and Weinstein, B. M. (2003) Angiogenic network formation in the developing vertebrate trunk. Development, 130: 5281-5290.

Lawson, N. D., Mugford, J. W., Diamond, B. A., and Weinstein, B. M. (2003) phospholipase C gamma-1 is required downstream of vascular endothelial growth factor during arterial development. Genes and Development, 17:1346-1351.

Lawson, N. D. and Weinstein, B. M. (2002) Arteries and veins: making a difference with zebrafish. Nature Reviews Genetics, 3:674-682

Weinstein, B. M., and Lawson, N. D. (2002) Arteries, veins, Notch, and VEGF. Cold Spring Harb Symp Quant Biol, 67: 155-162.

Lawson, N. D., Vogel, A., and Weinstein, B.M. (2002) sonic hedgehog and vascular endothelial growth factor act upstream of the Notch signaling pathway during arterial differentiation. Developmental Cell, 3:127-136.

Lawson, N. D., and Weinstein, B. M. (2002) In vivo imaging of vascular development using transgenic zebrafish. Developmental Biology, 248:307-318.

Roman, B. L., Pham, V. N., Lawson, N. D. et al. (2002) Disruption of acvrl1 increases endothelial cell number in zebrafish cranial vessels. Development, 129:3009-3019.

Lyons, S., Lawson, N. D., Li, L., Bennett, Jr., P., Weinstein, B. M., and Liu, P. P. (2002) A nonsense mutation in zebrafish gata1 causes the bloodless phenotype in vlad tepes. Proc. Natl. Acad. Sci. USA, 99: 5454-5459.

Lawson, N. D., Scheer, N., Pham, V., Kim, C-H., Campos-Ortega, J. A., Chitnis, A. B., and Weinstein, B. M. (2001) Notch signaling is required for arterial-venous differentiation during embryonic vascular development. Development, 128: 3675-3683.

Rotation Projects

Clone and characterize putative downstream components of the Vegf signaling pathway.
In vivo biochemical characterization of Plcg1 function downstream of Vegf.
Genetic characterization of the Notch signaling pathway during arterial differentiation using epistasis experiments with available transgenic and mutant zebrafish lines.
Isolation and characterization of artery or vein specific promoters.

Laboratory Personnel

For a current list of lab personnel, please visit our lab web page.

Academic Background

Nathan Lawson received his B.S. in Zoology from the University of Rhode Island in 1994, and his Ph.D. in Biology from Yale University in 1999. From 1999 to 2002, he was a National Research Council Postdoctoral Associate at the National Institutes of Health. Dr. Lawson joined the Program in Gene Function and Expression at the University of Massachusetts Medical School as an Assistant Professor in the fall of 2002.

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

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