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Research
General Information
ZIRC
ZFIN ID: ZDB-PERS-050519-12
Stewart, Rodney A.
Email: rodney.stewart@hci.utah.edu
URL: http://medicine.utah.edu/oncsci/faculty/rstewart.htm
Affiliation: Rodney Stewart Lab
Address: Huntsman Cancer Institute 2000 Circle of Hope Salt Lake City, UT 84112-5550 USA
Country: United States
Phone: (801) 587-5567
Fax: (801) 585-0900
Orcid ID:


BIOGRAPHY AND RESEARCH INTERESTS
Research Interests:

My laboratory studies mechanisms underlying cell survival and migration during embryogenesis and disease. We are particularly interested in embryonic signaling pathways that are re-activated in tumors to promote cancer metastasis. An excellent model of cell migration during development is the neural crest, a multipotent cell population that migrates extensively in the vertebrate embryo to generate a variety of cell types, including pigment cells, neurons, glia and elements of the craniofacial skeleton. Neural crest progenitors are initially generated in the neuroepithelium of the neural tube, so they must first undergo an epithelial-mesenchymal transition (EMT) to form premigratory neural crest cells. These cells then divide and navigate through a number of embryonic tissues that secrete potential pro-apoptotic signals, before arriving at their final destination to differentiate. Thus, neural crest cells have evolved mechanisms to coordinate a number of cellular processes that involve regulation of cell survival, proliferation and migration, as well as modifications of cell-cell adhesion that involve dynamic interactions with the extracellular matrix. Disrupting these processes during human development causes a number of congenital diseases (neurocristopathies), and cancers, such as melanoma and neuroblastoma. Importantly, recent studies have shown that ‘re-activation’ of neural crest transcription factors in primary tumors promotes tumor invasiveness and metastasis.
To study neural crest migration and metastasis, we use the zebrafish model because the optically clear embryos and adult pigment mutants allow fluorescently labeled cells and tumors to be monitored using real-time imaging techniques. In addition, the molecular pathways underlying mammalian embryonic development are highly conserved in zebrafish, and a number of zebrafish models of human diseases are now established, including neural crest-derived cancers. Also, cell transplantation experiments can be performed in embryos and adult fish, allowing cell autonomous and non-autonomous mechanisms of cell migration and metastasis to be investigated. Thus, the attributes of the zebrafish system provide a unique opportunity to determine how developmental mechanisms that control cell migration during development are subverted in pediatric diseases and cancer metastasis.


PUBLICATIONS
Sorrells, S., Nik, S., Casey, M., Cameron, R.C., Truong, H., Toruno, C., Gulfo, M., Lowe, A., Jette, C., Stewart, R.A., Bowman, T.V. (2018) Spliceosomal components protect embryonic neurons from R-loop-mediated DNA damage and apoptosis. Disease models & mechanisms. 11(2)
Casey, M.J., Stewart, R.A. (2017) Zebrafish as a model to study neuroblastoma development. Cell and tissue research. 372(2):223-232
Boer, E.F., Jette, C.A., Stewart, R.A. (2016) Neural Crest Migration and Survival Are Susceptible to Morpholino-Induced Artifacts. PLoS One. 11:e0167278
Modzelewska, K., Boer, E.F., Mosbruger, T.L., Picard, D., Anderson, D., Miles, R.R., Kroll, M., Oslund, W., Pysher, T.J., Schiffman, J.D., Jensen, R., Jette, C.A., Huang, A., Stewart, R.A. (2016) MEK Inhibitors Reverse Growth of Embryonal Brain Tumors Derived from Oligoneural Precursor Cells. Cell Reports. 17:1255-1264
Jimenez, L., Wang, J., Morrison, M.A., Whatcott, C., Soh, K.K., Warner, S., Bearss, D., Jette, C.A., Stewart, R.A. (2016) Phenotypic chemical screening using zebrafish neural crest reporters identifies retinoid acid as an inhibitor of epithelial morphogenesis. Disease models & mechanisms. 9(4):389-400
Morrison, M.A., Zimmerman, M.W., Look, A.T., Stewart, R.A. (2016) Studying the peripheral sympathetic nervous system and neuroblastoma in zebrafish. Methods in cell biology. 134:97-138
Boer, E.F., Howell, E.D., Schilling, T.F., Jette, C.A., Stewart, R.A. (2015) Fascin1-Dependent Filopodia are Required for Directional Migration of a Subset of Neural Crest Cells. PLoS Genetics. 11:e1004946
Toruno, C., Carbonneau, S., Stewart, R.A., and Jette, C. (2014) Interdependence of Bad and Puma during ionizing-radiation-induced apoptosis. PLoS One. 9(2):e88151
Sorrells, S., Toruno, C., Stewart, R.A., and Jette, C. (2013) Analysis of apoptosis in zebrafish embryos by whole-mount immunofluorescence to detect activated Caspase 3. Journal of visualized experiments : JoVE. (82):e51060
Pei, D., Luther, W., Wang, W., Paw, B.H., Stewart, R.A., and George, R.E. (2013) Distinct Neuroblastoma-associated Alterations of PHOX2B Impair Sympathetic Neuronal Differentiation in Zebrafish Models. PLoS Genetics. 9(6):e1003533
Zhu, S., Lee, J.S., Guo, F., Shin, J., Perez-Atayde, A.R., Kutok, J.L., Rodig, S.J., Neuberg, D.S., Helman, D., Feng, H., Stewart, R.A., Wang, W., George, R.E., Kanki, J.P., and Look, A.T. (2012) Activated ALK Collaborates with MYCN in Neuroblastoma Pathogenesis. Cancer Cell. 21(3):362-373
Sorrells, S., Carbonneau, S., Harrington, E., Chen, A.T., Hast, B., Milash, B., Pyati, U., Major, M.B., Zhou, Y., Zon, L.I., Stewart, R.A., Look, A.T., and Jette, C. (2012) Ccdc94 Protects Cells from Ionizing Radiation by Inhibiting the Expression of p53. PLoS Genetics. 8(8):e1002922
Bolli, N., Payne, E.M., Rhodes, J., Gjini, E., Johnston, A.B., Guo, F., Lee, J.S., Stewart, R.A., Kanki, J.P., Chen, A.T., Zhou, Y., Zon, L.I., and Look, A.T. (2011) cpsf1 is required for definitive HSC survival in zebrafish. Blood. 117(15):3996-4007
Murphy, D.A., Diaz, B., Bromann, P.A., Tsai, J.H., Kawakami, Y., Maurer, J., Stewart, R.A., Izpisúa-Belmonte, J.C., and Courtneidge, S.A. (2011) A Src-Tks5 Pathway Is Required for Neural Crest Cell Migration during Embryonic Development. PLoS One. 6(7):e22499
Stewart, R.A., Sanda, T., Widlund, H.R., Zhu, S., Swanson, K.D., Hurley, A.D., Bentires-Alj, M., Fisher, D.E., Kontaridis, M.I., Look, A.T., and Neel, B.G. (2010) Phosphatase-Dependent and -Independent Functions of Shp2 in Neural Crest Cells Underlie LEOPARD Syndrome Pathogenesis. Developmental Cell. 18(5):750-762
Stewart, R.A., Lee, J.S., Lachnit, M., Look, A.T., Kanki, J.P., and Henion, P.D. (2010) Chapter 5 - Studying peripheral sympathetic nervous system development and neuroblastoma in zebrafish. Methods in cell biology. 100:127-152
Jette, C.A., Flanagan, A.M., Ryan, J., Pyati, U.J., Carbonneau, S., Stewart, R.A., Langenau, D.M., Look, A.T., and Letai, A. (2008) BIM and other BCL-2 family proteins exhibit cross-species conservation of function between zebrafish and mammals. Cell death and differentiation. 15(6):1063-1072
Smolen, G.A., Schott, B.J., Stewart, R.A., Diederichs, S., Muir, B., Provencher, H.L., Look, A.T., Sgroi, D.C., Peterson, R.T., and Haber, D.A. (2007) A Rap GTPase interactor, RADIL, mediates migration of neural crest precursors. Genes & Development. 21(17):2131-2136
Montero-Balaguer, M., Lang, M.R., Sachdev, S.W., Knappmeyer, C., Stewart, R.A., De La Guardia, A., Hatzopoulos, A.K., and Knapik, E.W. (2006) The mother superior mutation ablates foxd3 activity in neural crest progenitor cells and depletes neural crest derivatives in zebrafish. Developmental dynamics : an official publication of the American Association of Anatomists. 235(12):3199-3212
Stewart, R.A., Arduini, B.L., Berghmans, S., George, R.E., Kanki, J.P., Henion, P.D., and Look, A.T. (2006) Zebrafish foxd3 is selectively required for neural crest specification, migration and survival. Developmental Biology. 292(1):174-188
Berghmans, S., Jette, C., Langenau, D., Hsu, K., Stewart, R., Look, T., and Kanki, J.P. (2005) Making waves in cancer research: new models in the zebrafish. Biotechniques. 39(2):227-237
Stewart, R.A., Look, A.T., Kanki, J.P., and Henion, P.D. (2004) Development of the peripheral sympathetic nervous system in zebrafish. The Zebrafish: Cellular and Developmental Biology,2nd Ed. Methods Cell Biol.. 76:237-260

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